Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 431
Filtrar
1.
Trials ; 22(1): 186, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33673867

RESUMO

BACKGROUND: Depression and anxiety impact up to 1 in 5 pregnant and postpartum women worldwide. Yet, as few as 20% of these women are treated with frontline interventions such as evidence-based psychological treatments. Major barriers to uptake are the limited number of specialized mental health treatment providers in most settings, and problems with accessing in-person care, such as childcare or transportation. Task sharing of treatment to non-specialist providers with delivery on telemedicine platforms could address such barriers. However, the equivalence of these strategies to specialist and in-person models remains unproven. METHODS: This study protocol outlines the Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) randomized trial. SUMMIT is a pragmatic, non-inferiority test of the comparable effectiveness of two types of providers (specialist vs. non-specialist) and delivery modes (telemedicine vs. in-person) of a brief, behavioral activation (BA) treatment for perinatal depressive and anxiety symptoms. Specialists (psychologists, psychiatrists, and social workers with ≥ 5 years of therapy experience) and non-specialists (nurses and midwives with no formal training in mental health care) were trained in the BA protocol, with the latter supervised by a BA expert during treatment delivery. Consenting pregnant and postpartum women with Edinburgh Postnatal Depression Scale (EPDS) score of ≥ 10 (N = 1368) will be randomized to one of four arms (telemedicine specialist, telemedicine non-specialist, in-person specialist, in-person non-specialist), stratified by pregnancy status (antenatal/postnatal) and study site. The primary outcome is participant-reported depressive symptoms (EPDS) at 3 months post-randomization. Secondary outcomes are maternal symptoms of anxiety and trauma symptoms, perceived social support, activation levels and quality of life at 3-, 6-, and 12-month post-randomization, and depressive symptoms at 6- and 12-month post-randomization. Primary analyses are per-protocol and intent-to-treat. The study has successfully continued despite the COVID-19 pandemic, with needed adaptations, including temporary suspension of the in-person arms and ongoing randomization to telemedicine arms. DISCUSSION: The SUMMIT trial is expected to generate evidence on the non-inferiority of BA delivered by a non-specialist provider compared to specialist and telemedicine compared to in-person. If confirmed, results could pave the way to a dramatic increase in access to treatment for perinatal depression and anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT04153864 . Registered on November 6, 2019.


Assuntos
Ansiedade/terapia , Depressão Pós-Parto/terapia , Depressão/terapia , Acesso aos Serviços de Saúde , Complicações na Gravidez/terapia , Psicoterapia/métodos , Telemedicina/métodos , Assistência à Saúde/métodos , Estudos de Equivalência como Asunto , Feminino , Humanos , Serviços de Saúde Materna , Serviços de Saúde Mental/organização & administração , Tocologia , Enfermeiras e Enfermeiros , Ensaios Clínicos Pragmáticos como Assunto , Gravidez , Escalas de Graduação Psiquiátrica , Psiquiatria , Psicologia , Assistentes Sociais , Especialização
2.
Trials ; 22(1): 172, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648568

RESUMO

OBJECTIVES: The primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior to a 6 mg dose in adult patients with moderate or severe ARDS due to confirmed COVID-19. The secondary objective is to investigate the efficacy and safety of dexamethasone 20 mg versus dexamethasone 6 mg. The exploratory objective of this study is to assess long-term consequences on mortality and quality of life at 180 and 360 days. TRIAL DESIGN: REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice. PARTICIPANTS: The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. INCLUSION CRITERIA: Subjects will be eligible for the trial if they meet all of the following criteria: 1. Adult (≥18 years of age) at time of enrolment; 2. Present COVID-19 (infection confirmed by RT-PCR or antigen testing); 3. Intubation/mechanical ventilation or ongoing high-flow nasal cannula (HFNC) oxygen therapy; 4. Moderate or severe ARDS according to Berlin criteria: • Moderate - PaO2/FiO2 100-200 mmHg; • Severe - PaO2/FiO2 < 100 mmHg; 5. Admission to ICU in the last 24 hours. EXCLUSION CRITERIA: Subjects will not be eligible for the trial if they meet any of the following criteria: 1. Known allergy/hypersensitivity to dexamethasone or excipients of the investigational medicinal product (e.g. parabens, benzyl alcohol); 2. Fulfilled criteria for ARDS for ≥14 days at enrolment; 3. Pregnancy or breastfeeding; 4. Unwillingness to comply with contraception measurements from enrolment until at least 1 week after the last dose of dexamethasone (sexual abstinence is considered an adequate contraception method); 5. End-of-life decision or patient is expected to die within next 24 hours; 6. Decision not to intubate or ceilings of care in place; 7. Immunosuppression and/or immunosuppressive drugs in medical history: a) Systemic immunosuppressive drugs or chemotherapy in the past 30 days; b) Systemic corticosteroid use before hospitalization; c) Any dose of dexamethasone during the present hospital stay for COVID-19 for ≥5 days before enrolment; d) Systemic corticosteroids during present hospital stay for conditions other than COVID-19 (e.g. septic shock); 8. Current haematological or generalized solid malignancy; 9. Any contraindication for corticosteroid administration, e.g. • intractable hyperglycaemia; • active gastrointestinal bleeding; • adrenal gland disorders; • presence of superinfection diagnosed with locally established clinical and laboratory criteria without adequate antimicrobial treatment; 10. Cardiac arrest before ICU admission; 11. Participation in another interventional trial in the last 30 days. INTERVENTION AND COMPARATOR: Dexamethasone solution for injection/infusion is the investigational medicinal product as well as the comparator. The trial will assess two doses, 20 mg (investigational) vs 6 mg (comparator). Patients in the intervention group will receive dexamethasone 20 mg intravenously once daily on day 1-5, followed by dexamethasone 10 mg intravenously once daily on day 6-10. Patients in the control group will receive dexamethasone 6 mg day 1-10. All authorized medicinal products containing dexamethasone in the form of solution for i.v. injection/infusion can be used. MAIN OUTCOMES: Primary endpoint: Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation. SECONDARY ENDPOINTS: a) Mortality from any cause at 60 days after randomisation; b) Dynamics of inflammatory marker (C-Reactive Protein, CRP) change from Day 1 to Day 14; c) WHO Clinical Progression Scale at Day 14; d) Adverse events related to corticosteroids (new infections, new thrombotic complications) until Day 28 or hospital discharge; e) Independence at 90 days after randomisation assessed by Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days through telephone structured interviews using the Barthel Index. RANDOMISATION: Randomisation will be carried out within the electronic case report form (eCRF) by the stratified permuted block randomisation method. Allocation sequences will be prepared by a statistician independent of the study team. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomisation process. The following stratification factors will be applied: • Age <65 and ≥ 65; • Charlson Comorbidity index (CCI) <3 and ≥3; • CRP <150 mg/L and ≥150 mg/L • Trial centre. Patients will be randomised in a 1 : 1 ratio into one of the two treatment arms. Randomisation through the eCRF will be available 24 hours every day. BLINDING (MASKING): This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size is calculated to detect the difference of 3 VFDs at 28 days (primary efficacy endpoint) between the two treatment arms with a two-sided type I error of 0.05 and power of 80%. Based on data from a multi-centre randomised controlled trial in COVID-19 ARDS patients in Brazil and a multi-centre observational study from French and Belgian ICUs regarding moderate to severe ARDS related to COVID-19, investigators assumed a standard deviation of VFD at 28 days as 9. Using these assumptions, a total of 142 patients per treatment arm would be needed. After adjustment for a drop-out rate, 150 per treatment arm (300 patients per study) will be enrolled. TRIAL STATUS: This is protocol version 1.1, 15.01.2021. The trial is due to start on 2 February 2021 and recruitment is expected to be completed by December 2021. TRIAL REGISTRATION: The study protocol was registered on EudraCT No.:2020-005887-70, and on December 11, 2020 on ClinicalTrials.gov (Title: Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19 (REMED)) Identifier: NCT04663555 with a last update posted on February 1, 2021. FULL PROTOCOL: The full protocol (version 1.1) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the standard formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
/terapia , Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Respiração Artificial , /terapia , /complicações , Ensaios Clínicos Fase II como Assunto , Progressão da Doença , Relação Dose-Resposta a Droga , Estudos de Equivalência como Asunto , Humanos , Tempo de Internação , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , /etiologia
3.
Lancet Oncol ; 22(3): 332-340, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33539729

RESUMO

BACKGROUND: The optimal radiotherapy dose for indolent non-Hodgkin lymphoma is uncertain. We aimed to compare 24 Gy in 12 fractions (representing the standard of care) with 4 Gy in two fractions (low-dose radiation). METHODS: FoRT (Follicular Radiotherapy Trial) is a randomised, multicentre, phase 3, non-inferiority trial at 43 study centres in the UK. We enrolled patients (aged >18 years) with indolent non-Hodgkin lymphoma who had histological confirmation of follicular lymphoma or marginal zone lymphoma requiring radical or palliative radiotherapy. No limit on performance status was stipulated, and previous chemotherapy or radiotherapy to another site was permitted. Radiotherapy target sites were randomly allocated (1:1) either 24 Gy in 12 fractions or 4 Gy in two fractions using minimisation and stratified by histology, treatment intent, and study centre. Randomisation was centralised through the Cancer Research UK and University College London Cancer Trials Centre. Patients, treating clinicians, and investigators were not masked to random assignments. The primary endpoint was time to local progression in the irradiated volume based on clinical and radiological evaluation and analysed on an intention-to-treat basis. The non-inferiority threshold aimed to exclude the chance that 4 Gy was more than 10% inferior to 24 Gy in terms of local control at 2 years (HR 1·37). Safety (in terms of adverse events) was analysed in patients who received any radiotherapy and who returned an adverse event form. FoRT is registered with ClinicalTrials.gov, NCT00310167, and the ISRCTN Registry, ISRCTN65687530, and this report represents the long-term follow-up. FINDINGS: Between April 7, 2006, and June 8, 2011, 614 target sites in 548 patients were randomly assigned either 24 Gy in 12 fractions (n=299) or 4 Gy in two fractions (n=315). At a median follow-up of 73·8 months (IQR 61·9-88·0), 117 local progression events were recorded, 27 in the 24 Gy group and 90 in the 4 Gy group. The 2-year local progression-free rate was 94·1% (95% CI 90·6-96·4) after 24 Gy and 79·8% (74·8-83·9) after 4 Gy; corresponding rates at 5 years were 89·9% (85·5-93·1) after 24 Gy and 70·4% (64·7-75·4) after 4 Gy (hazard ratio 3·46, 95% CI 2·25-5·33; p<0·0001). The difference at 2 years remains outside the non-inferiority margin of 10% at -13·0% (95% CI -21·7 to -6·9). The most common events at week 12 were alopecia (19 [7%] of 287 sites with 24 Gy vs six [2%] of 301 sites with 4 Gy), dry mouth (11 [4%] vs five [2%]), fatigue (seven [2%] vs five [2%]), mucositis (seven [2%] vs three [1%]), and pain (seven [2%] vs two [1%]). No treatment-related deaths were reported. INTERPRETATION: Our findings at 5 years show that the optimal radiotherapy dose for indolent lymphoma is 24 Gy in 12 fractions when durable local control is the aim of treatment. FUNDING: Cancer Research UK.


Assuntos
Linfoma de Zona Marginal Tipo Células B/radioterapia , Linfoma Folicular/radioterapia , Radioterapia/mortalidade , Idoso , Estudos de Equivalência como Asunto , Feminino , Seguimentos , Raios gama , Humanos , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
4.
Trials ; 22(1): 131, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33573681

RESUMO

OBJECTIVES: The main objective of this study is to evaluate the effect of intravenous lidocaine on gas exchange and inflammation in acute respiratory distress syndrome due or not to Covid-19 pneumonia. TRIAL DESIGN: This is a prospective monocentric, randomized, quadruple-blinded and placebo-controlled superiority trial. This phase 3 clinical study is based on two parallel groups received either intravenous lidocaine 2% or intravenous NaCl 0.9%. PARTICIPANTS: This study has been conducted at the University Hospitals of Strasbourg (medical and surgical Intensive Care Units in Hautepierre Hospital) since the 4th November 2020. The participants are 18 years-old and older, hospitalized in ICU for a moderate to severe ARDS according to the Berlin definition; they have to be intubated and sedated for mechanical protective ventilation. All participants are affiliated to the French Social security system and a dosage of beta HCG has to be negative for women of child bearing age . For the Covid-19 subgroup, the SARS-CoV2 infection is proved by RT-PCR <7 days before admission and/or another approved diagnostic technique and/or typical CT appearance pneumonia. The data are prospectively collected in e-Case Report Forms and extracted from clinical files. INTERVENTION AND COMPARATOR: The participants are randomised in two parallel groups with a 1:1 ratio. In the experimental group, patients receive intravenous lidocaine 2% (20mg/mL) (from FRESENIUS KABI France); the infusion protocol provide a bolus of 1 mg/kg (ideal weight), followed by 3 mg/kg/h for the first hour, 1.5 mg/kg/h for the second hour, 0.72 mg/kg/h for the next 22 hours and then 0.6 mg/kg/h for 14 days at most or 24 hours after extubation or ventilator-weaning. The patients in the control group receive intravenous NaCl 0.9% (9 mg/mL) (from Aguettant, France) as placebo comparator; the infusion protocol provide a bolus of 0.05 mL/kg (ideal weight), followed by 0.15 mL/kg/h for the first hour, 0.075 mL/kg/h for the second hour, 0.036 mL/kg/h for the next 22 hours, and the 0.03 mL/kg/h for up to 14 days or 24 hours after extubation or ventilator-weaning. Lidocaine level is assessed at H4, D2, D7 and D14 to prevent local anesthetics systemic toxicity. Clinical data and biological samples are collected to assess disease progression. MAIN OUTCOMES: The primary outcome is the evolution of alveolar-capillary gas exchange measured by the PaO2/FiO2 ratio after two days of treatment. The secondary endpoints of the study include the following: Evolution of PaO2/FiO2 ratio at admission and after 21 days of treatment Number of ventilator-free days Anti-inflammatory effects by dosing inflammatory markers at different timepoints (ferritin, bicarbonate, CRP, PCT, LDH, IL-6, Troponin HS, triglycerides, complete blood count, lymphocytes) Anti-thrombotic effects by dosing platelets, aPTT, fibrinogen, D-dimers, viscoelastic testing and identification of all thromboembolic events up to 4 weeks. Plasmatic concentration of lidocaine and albumin Incidence of adverse events like cardiac rhythm disorders, need of vasopressors, any modification of the QRS, QTc or PR intervals every day Ileus recovery time Consumption of hypnotics, opioids, neuromuscular blockers. Lengths of stay in the ICU, incidence of reintubation and complications due to intensive care unit care (mortality until 90 days, pneumothorax, bacterial pneumopathy, bronchospasm, cardiogenic shock, acute renal failure, need of renal dialysis, delirium, atrial fibrillation, stroke (CAM-ICU score), tetraplegia (MCR score)). Incidence of cough and sore throat at extubation or ventilator-weaning and within 24 hours. All these outcomes will be evaluated according to positivity to Sars-Cov-2. RANDOMISATION: The participants who meet the inclusion criteria and have signed written informed consent will be randomly allocated using a computer-generated random number to either intervention group or control group. The distribution ratio of the two groups will be 1:1, with a stratification according to positivity to Sars-Cov-2. BLINDING (MASKING): All participants, care providers, investigator and outcomes assessor are blinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We planned to randomize fifty participants in each group, 100 participants total. TRIAL STATUS: The amended protocol version 2.1 was approved by the Ethics Committee "Comité de Protection des Personnes Sud-Méditerranée II on January 8, 2021 and by the Commission Nationale de l'Informatique et des Libertés (CNIL) on November 10, 2020. The study is currently recruiting participants; the recruitment started in November 2020 and the planned recruitment period is three years. TRIAL REGISTRATION: The trial was registered on clinicaltrials.gov on October 30, 2020 and identified by number NCT04609865 . FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
/tratamento farmacológico , Lidocaína/uso terapêutico , Bloqueadores do Canal de Sódio Disparado por Voltagem/uso terapêutico , Administração Intravenosa , /fisiopatologia , Ensaios Clínicos Fase III como Assunto , Estudos de Equivalência como Asunto , Humanos , Inflamação/sangue , Troca Gasosa Pulmonar , Ensaios Clínicos Controlados Aleatórios como Assunto , /fisiopatologia , Resultado do Tratamento
6.
Trials ; 22(1): 98, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509268

RESUMO

BACKGROUND: Sweden is home to a large and growing population of refugee youths who may be at risk of mental health problems such as post-traumatic stress disorder (PTSD). Thus, there is a need for interventions that address mental health problems in these populations. Schools have been identified as an ideal setting for delivering such interventions as they offer a non-stigmatizing space and are often central to young refugees' social networks. The RefugeesWellSchool trial in Sweden will investigate an intervention comprising two programmes: Teaching Recovery Techniques (TRT) and In-service Teacher Training (INSETT), delivered in a school setting, among refugee youth. TRT is a group-based programme for children and adolescents, informed by Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). INSETT is a multi-module course for teachers providing information on trauma and the refugee experience to build teachers' cultural competence and capacity for supporting refugee youths in schools. METHODS: This trial employs a cluster randomized-control design with two arms: (1) the intervention arm in which the TRT and INSETT programmes are offered (n = 350), (2) the wait-list control arm (n = 350) in which services are provided as usual until the TRT and INSETT programmes are offered approximately six months later. Data will be collected prior to the intervention, immediately following the intervention, and at three months post-intervention. Outcomes for the trial arms will be compared using linear mixed models or ANCOVA repeated measures as well as the Reliable Change Index (RCI). DISCUSSION: This study will provide knowledge about the effectiveness of an intervention comprising two programmes: a group-based programme for youth reporting symptoms of PTSD and a training course for teachers, in order to build their competence and ability to support refugee youths in schools. TRIAL REGISTRATION: ISRCTN, ISRCTN48178969 , Retrospectively registered 20/12/2019.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Promoção da Saúde/organização & administração , Refugiados/psicologia , Serviços de Saúde Escolar/organização & administração , Transtornos de Estresse Pós-Traumáticos/terapia , Adolescente , Terapia Cognitivo-Comportamental/organização & administração , Estudos de Equivalência como Asunto , Feminino , Implementação de Plano de Saúde , Promoção da Saúde/métodos , Humanos , Masculino , Saúde Mental , Avaliação de Programas e Projetos de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Suécia , Capacitação de Professores/métodos , Capacitação de Professores/organização & administração , Resultado do Tratamento
7.
BMJ Open ; 10(11): e041520, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33177145

RESUMO

INTRODUCTION: Prone positioning (PP) is an effective first-line intervention to treat patients with moderate to severe acute respiratory distress syndrome (ARDS) receiving invasive mechanical ventilation, as it improves gas exchanges and reduces mortality. The use of PP in awake spontaneous breathing patients with ARDS secondary to COVID-19 was reported to improve oxygenation in few retrospective trials with small sample size. High-level evidence of awake PP for hypoxaemic patients with COVID-19 patients is still lacking. METHODS AND ANALYSIS: The protocol of this meta-trial is a prospective collaborative individual participant data meta-analysis of randomised controlled open label superiority trials. This design is particularly adapted to a rapid scientific response in the pandemic setting. It will take place in multiple sites, among others in USA, Canada, Ireland, France and Spain. Patients will be followed up for 28 days. Patients will be randomised to receive whether awake PP and nasal high flow therapy or standard medical treatment and nasal high flow therapy. Primary outcome is defined as the occurrence rate of tracheal intubation or death up to day 28. An interim analysis plan has been set up on aggregated data from the participating research groups. ETHICS AND DISSEMINATION: Ethics approvals were obtained in all participating countries. Results of the meta-trial will be submitted for publication in a peer-reviewed journal. Each randomised controlled trial was registered individually, as follows: NCT04325906, NCT04347941, NCT04358939, NCT04395144 and NCT04391140.


Assuntos
Infecções por Coronavirus/terapia , Hipóxia/terapia , Oxigenoterapia/métodos , Posicionamento do Paciente/métodos , Pneumonia Viral/terapia , Decúbito Ventral , Betacoronavirus , Cânula , Estudos de Equivalência como Asunto , Humanos , Metanálise como Assunto , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , Vigília
8.
Trials ; 21(1): 770, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907635

RESUMO

OBJECTIVES: The OVID study will demonstrate whether prophylactic-dose enoxaparin improves survival and reduces hospitalizations in symptomatic ambulatory patients aged 50 or older diagnosed with COVID-19, a novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and coagulation activation. TRIAL DESIGN: The OVID study is conducted as a multicentre open-label superiority randomised controlled trial. PARTICIPANTS: Inclusion Criteria 1. Signed patient informed consent after being fully informed about the study's background. 2. Patients aged 50 years or older with a positive test for SARS-CoV2 in the past 5 days and eligible for ambulatory treatment. 3. Presence of respiratory symptoms (i.e. cough, sore throat, or shortness of breath) or body temperature >37.5° C. 4. Ability of the patient to travel to the study centre by private transportation, performed either by an accompanying person from the same household or by the patient themselves 5. Ability to comply with standard hygiene requirements at the time of in-hospital visit, including a face mask and hand disinfectant. 6. Ability to walk from car to study centre or reach it by wheelchair transport with the help of an accompanying person from the same household also complying with standard hygiene requirements. 7. Ability to self-administer prefilled enoxaparin injections after instructions received at the study centre or availability of a person living with the patient to administer enoxaparin. Exclusion Criteria 1. Any acute or chronic condition posing an indication for anticoagulant treatment, e.g. atrial fibrillation, prior venous thromboembolism (VTE), acute confirmed symptomatic VTE, acute coronary syndrome. 2. Anticoagulant thromboprophylaxis deemed necessary in view of the patient's history, comorbidity or predisposing strong risk factors for thrombosis: a. Any of the following events occurring in the prior 30 days: fracture of lower limb, hospitalization for heart failure, hip/knee replacement, major trauma, spinal cord injury, stroke, b. previous VTE, c. histologically confirmed malignancy, which was diagnosed or treated (surgery, chemotherapy, radiotherapy) in the past 6 months, or recurrent, or metastatic, or inoperable. 3. Any clinically relevant bleeding (defined as bleeding requiring hospitalization, transfusion, surgical intervention, invasive procedures, occurring in a critical anatomical site, or causing disability) within 30 days prior to randomization or sign of acute bleeding. 4. Intracerebral bleeding at any time in the past or signs/symptoms consistent with acute intracranial haemorrhage. 5. Haemoglobin <8 g/dL and platelet count <50 x 109 cells/L confirmed by recent laboratory test (<90 days). 6. Subjects with any known coagulopathy or bleeding diathesis, including known significant liver disease associated with coagulopathy. 7. Severe renal insufficiency (baseline creatinine clearance <30 mL/min calculated using the Cockcroft-Gault formula) confirmed by recent laboratory test (<90 days). 8. Contraindications to enoxaparin therapy, including prior heparin-induced thrombocytopenia and known hypersensitivity. 9. Current use of dual antiplatelet therapy. 10. Participation in other interventional studies over the past 30 days. 11. Non-compliance or inability to adhere to treatment or lack of a family environment or support system for home treatment. 12. Cognitive impairment and/or inability to understand information provided in the study information. Patient enrolment will take place at seven Swiss centres, including five university hospitals and two large cantonal hospitals. INTERVENTION AND COMPARATOR: Patients randomized to the intervention group will receive subcutaneous enoxaparin at the recommended dose of 4,000 IU anti-Xa activity (40 mg/0.4 ml) once daily for 14 days. Patients randomized to the comparator group will receive no anticoagulation. MAIN OUTCOMES: Primary outcome: a composite of any hospitalization or all-cause death occurring within 30 days of randomization. SECONDARY OUTCOMES: (i) a composite of cardiovascular events, including deep vein thrombosis (including catheter-associated), pulmonary embolism, myocardial infarction/myocarditis, arterial ischemia including mesenteric and extremities, acute splanchnic vein thrombosis, or ischemic stroke within 14 days, 30 days, and 90 days of randomization; (ii) each component of the primary efficacy outcome, within 14 days, 30 days, and 90 days of randomization; (iii) net clinical benefit (accounting for the primary efficacy outcome, composite cardiovascular events, and major bleeding), within 14 days, 30 days, and 90 days of enrolment; (iv) primary efficacy outcome, within 14 days, and 90 days of enrolment; (v) disseminated intravascular coagulation (ISTH criteria, in-hospital diagnosis) within 14 days, 30 days, and 90 days of enrolment. RANDOMISATION: Patients will undergo block stratified randomization (by age: 50-70 vs. >70 years; and by study centre) with a randomization ratio of 1:1 with block sizes varying between 4 and 8. Randomization will be performed after the signature of the informed consent for participation and the verification of the eligibility criteria using the electronic data capture software (REDCAP, Vanderbilt University, v9.1.24). BLINDING (MASKING): In this open-label study, no blinding procedures will be used. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size calculation is based on the parameters α = 0.05 (2-sided), power: 1-ß = 0.8, event rate in experimental group, pexp = 0.09 and event rate in control group, pcon = 0.15. The resulting total sample size is 920. To account for potential dropouts, the total sample size was fixed to 1000 with 500 patients in the intervention group and 500 in the control group. TRIAL STATUS: Protocol version 1.0, 14 April 2020. Protocol version 3.0, 18 May 2020 Recruiting start date: June 2020. Last Patient Last Visit: March 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04400799 First Posted: May 26, 2020 Last Update Posted: July 16, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Anticoagulantes/administração & dosagem , Betacoronavirus/patogenicidade , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Enoxaparina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Trombose/prevenção & controle , Anticoagulantes/efeitos adversos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Enoxaparina/efeitos adversos , Estudos de Equivalência como Asunto , Interações Hospedeiro-Patógeno , Humanos , Estudos Multicêntricos como Assunto , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Trombose/sangue , Trombose/diagnóstico , Trombose/virologia , Fatores de Tempo , Resultado do Tratamento
9.
Stroke Vasc Neurol ; 5(3): 311-314, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32994371

RESUMO

BACKGROUNDS: Embolic stroke is one of the main mechanisms of ischaemic stroke. Even if treated with recommended antithrombotic agents, stroke recurrence remains high. The Shuxuetong injection, a purified extract of traditional Chinese medicine widely used for thrombus diseases in clinical practice in China, could be a promising agent to prevent stroke recurrence. AIMS: To describe the design of the Shuxuetong injection for prevention of recurrence in acute ischaemic stroke with embolism mechanisms. DESIGN: The Shuxuetong for Prevention of recurrence in Acute Cerebrovascular events with Embolism (SPACE) trial is a multicentre, randomised, double-blind, placebo-controlled, parallel-group, superiority trial to evaluate the efficacy and safety of Shuxuetong injection in reducing recurrence or silent new ischaemic lesions on patients with acute embolic stroke within 10 days. An estimated 2416 patients with embolic stroke within 72 hours of symptom onset from 80 hospitals will be randomly assigned to one of two groups receiving Shuxuetong injection or placebo injection for 10 days. The primary endpoint is symptomatic or asymptomatic new cerebral infarction within 10 days after randomisation. CONCLUSION: The SPACE Trial will provide valuable evidence for the efficacy and safety of Shuxuetong injection for the prevention of stroke recurrence in patients with imaging-defined embolic stroke. CLINICAL TRIAL REGISTRATION: NCT03090113.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Embolia Intracraniana/tratamento farmacológico , Prevenção Secundária , Acidente Vascular Cerebral/tratamento farmacológico , Adolescente , Adulto , Idoso , Isquemia Encefálica/diagnóstico , China , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Estudos de Equivalência como Asunto , Feminino , Humanos , Injeções , Embolia Intracraniana/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Recidiva , Acidente Vascular Cerebral/diagnóstico , Resultado do Tratamento , Adulto Jovem
10.
PLoS One ; 15(9): e0238024, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32991606

RESUMO

INTRODUCTION: At present, information about clinical efficacy and adverse events of controlled release (CR) form of pelubiprofen, a prodrug of 2-arylopropionic acid with relatively selective effects on cyclooxygenase-2 activity, remains scarce. In this study, we sought to determine non-inferiority of pelubiprofen CR 90 mg/day compared to aceclofenac 200 mg/day regarding clinical efficacy and adverse events after a 4-week course of medication in the patients with symptomatic knee osteoarthritis. MATERIALS AND METHODS: A total of 191 patients were randomly assigned to take either pelubiprofen CR 90 mg (n = 95) or aceclofenac 200 mg (n = 96). The primary outcome variable was non-inferiority of pain reduction between baseline and week 4 when assessed using a 100 mm pain visual analogue scale (VAS). Pelubiprofen was considered non-inferior to aceclofenac if the upper limit of the one-sided 97.5% confidence interval for the difference in terms of pain VAS was above 15 mm (the average change of pain VAS in the pelubiprofen group-pain VAS reduction in the aceclofenac group). Secondary outcome variables were the changes in 100 mm pain VAS at week 2 versus baseline, K-Western Ontario, and McMaster University Arthritis Index (K-WOMAC) changes at weeks 2 and 4 as compared to baseline, patient global assessment at weeks 2 and 4. The frequency and amount of rescue medicine usage at weeks 2 and 4 were also evaluated as the secondary outcome variable. For safety analysis, adverse events, clinical laboratory tests, vital signs, and physical examinations were assessed and conducted at each follow-up visit. RESULTS: At week 4, the pain VAS values were significantly reduced in both groups receiving either pelubiprofen CR 90 mg or aceclofenac 200 mg as compared to the baseline. However, the pelubiprofen group and the aceclofenac group respectively showed the pain VAS changes of -22 and -21.9 in the pre-protocol set and -20.8 and -21.7 in the full analysis set, confirming non-inferiority. The pelubiprofen CR 90 mg showed a reduced incidence of adverse events compared to the aceclofenac 200 mg (p = 0.005). CONCLUSIONS: Pelubiprofen CR 90 mg is as effective as aceclofenac 200 mg with reduced adverse events for the treatment of symptomatic knee osteoarthritis.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Diclofenaco/análogos & derivados , Osteoartrite do Joelho/tratamento farmacológico , Fenilpropionatos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diclofenaco/uso terapêutico , Método Duplo-Cego , Estudos de Equivalência como Asunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Medição da Dor , Segurança do Paciente , Resultado do Tratamento
11.
Medicine (Baltimore) ; 99(35): e21992, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871950

RESUMO

BACKGROUND: Diabetic macular edema (DME) can cause severe vision impairments for patients with diabetes. Recently, Conbercept has shown efficacy on DME with 3-monthly loading dose injection and pro re nata (PRN, 3+PRN) thereafter in retrospectivetrials. Furthermore, there are some other approaches have been recommended such as 2mg bimonthly (2q8) after 5 initial doses, or Conbercept 0.5mg treat-and-extend, however, some patients still have recurrence of the disease after treatment. Therefore, in order to identify more efficacy and safety approach on Conbercept inpatients with DME, a randomized controlled trial will be performed with 6-monthly loading dose injection and PRN (6+PRN) compared with 3+PRN treatments. METHODS: This study is a multicenter, randomized control trial of Conbecept treating DME in China. Patients with type 2 diabetes suffered from DEM who already planned to receive Conbercept treatment will be recruited. All subjects will be randomized divided into either a study agent treatment group (6+PRN) or a control group (3+PRN), and observes the subjects for 48 weeks after initiation of treatment. RESULTS: This study will provide a new powerful evidence of the efficacy and safety of Conbecept treating DME. DISCUSSION: This RTC study will determine whether multiple treatments of Conbercept provide better effectiveness in patients with DME. TRIAL REGISTRATION NUMBER: ChiCTR2000032728.


Assuntos
Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Angiografia , Estudos de Equivalência como Asunto , Humanos , Estudos Multicêntricos como Assunto , Tomografia de Coerência Óptica
12.
Sensors (Basel) ; 20(17)2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32872310

RESUMO

The non-invasive estimation of blood oxygen saturation (SpO2) by pulse oximetry is of vital importance clinically, from the detection of sleep apnea to the recent ambulatory monitoring of hypoxemia in the delayed post-infective phase of COVID-19. In this proof of concept study, we set out to establish the feasibility of SpO2 measurement from the ear canal as a convenient site for long term monitoring, and perform a comprehensive comparison with the right index finger-the conventional clinical measurement site. During resting blood oxygen saturation estimation, we found a root mean square difference of 1.47% between the two measurement sites, with a mean difference of 0.23% higher SpO2 in the right ear canal. Using breath holds, we observe the known phenomena of time delay between central circulation and peripheral circulation with a mean delay between the ear and finger of 12.4 s across all subjects. Furthermore, we document the lower photoplethysmogram amplitude from the ear canal and suggest ways to mitigate this issue. In conjunction with the well-known robustness to temperature induced vasoconstriction, this makes conclusive evidence for in-ear SpO2 monitoring being both convenient and superior to conventional finger measurement for continuous non-intrusive monitoring in both clinical and everyday-life settings.


Assuntos
Meato Acústico Externo , Hipóxia/diagnóstico , Monitorização Fisiológica/instrumentação , Oximetria/instrumentação , Fotopletismografia/instrumentação , Dispositivos Eletrônicos Vestíveis , Adulto , Betacoronavirus/fisiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Estudos de Equivalência como Asunto , Estudos de Viabilidade , Feminino , Dedos , Humanos , Hipóxia/sangue , Masculino , Monitorização Fisiológica/métodos , Oximetria/métodos , Oxigênio/análise , Oxigênio/sangue , Pandemias , Fotopletismografia/métodos , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Adulto Jovem
13.
Am Heart J ; 227: 111-117, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32739537

RESUMO

BACKGROUND: Complete revascularization in patients with an acute coronary syndrome and multivessel disease is superior compared to culprit-only treatment. However, it is unknown whether direct complete or staged complete revascularization should be pursued. METHODS: The BIOVASC study is an investigator-initiated, prospective, multicenter, randomized, 2-arm, international, open-label, noninferiority trial. We will randomize 1,525 patients 1:1 to immediate complete revascularization (experimental arm) or culprit-only plus staged complete revascularization (control arm). Patients will be enrolled in approximately 30 sites in Belgium, Italy, the Netherlands, and Spain. The primary end point is a composite of all-cause mortality, nonfatal myocardial infarction, any unplanned ischemia-driven revascularization (excluding staged procedures in the control arm at the predetermined time), and cerebrovascular events (MACCE) at 1 year post index procedure. CONCLUSIONS: The BIOVASC study aims to further refine the treatment algorithm for acute coronary syndrome patients with multivessel disease in terms of optimal timing for complete revascularization (Clinicaltrials.gov NCT03621501).


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Stents Farmacológicos , Intervenção Coronária Percutânea , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Sirolimo/administração & dosagem , Implantes Absorvíveis , Estudos de Equivalência como Asunto , Humanos , Estudos Multicêntricos como Assunto , Polímeros , Estudos Prospectivos , Desenho de Prótese
14.
Medicine (Baltimore) ; 99(30): e21151, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791688

RESUMO

BACKGROUND: The introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) into clinical practice has dramatically improve the clinical outcomes of individuals with rheumatoid arthritis (RA). However, bDMARDs are associated with high costs, which has resulted in restricted treatment access and a burden on medical insurance finances. Although biosimilars offer cost-saving, their effectiveness and safety must be established in Post-Marketing Surveillance (PMS). Infliximab (IFX), a chimeric monoclonal antibody to TNF-alpha, is the first bDMARD; its biosimilar, CT-P13, is the first biosimilar DMARD approved for RA treatment in Japan. We will evaluate whether switching from originator IFX to CT-P13 is not inferior for maintaining non-clinical relapse to continued treatment with originator IFX in RA patients achieving clinical remission. METHODS/DESIGN: This study is an interventional, multicenter, open-label, single-arm against historical control and noninferiority clinical trial with a 24-week follow-up. Eighty RA patients who are treated by originator IFX for ≥24 weeks and are achieving clinical remission will be included. Patients will be switched to CT-P13 with the unchanged dosing regimen. We will evaluate disease activity by measuring clinical disease activity indices and by using musculoskeletal ultrasound (MSUS). The primary endpoint is the ratio of patients who experience a nonclinical relapse during the study period. Important secondary endpoints are the changes from the baseline of the MSUS scores. We will also comprehensively analyze the serum levels of many biomarkers such as cytokines and chemokines. DISCUSSION: The study results are expected to show the noninferiority of switching to CT-P13 over the continuation of originator IFX. The strength of this study is its prospective evaluation of therapeutic efficacy using not only clinical disease activity indices but also MSUS to accurately and objectively evaluate disease activity at the joint level among patients drawn from multiple centers with a standardized evaluation by MSUS. We will explore whether parameters at baseline can predict a nonclinical relapse after switching from originator IFX to CT-P13 by integrating multilateral assessments, i.e., clinical disease activity indices, MSUS findings, and serum biomarkers. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on October 11, 2019 as jRCTs071190030.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/uso terapêutico , Quimiocinas/sangue , Infliximab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico por imagem , Biomarcadores/sangue , Substituição de Medicamentos , Estudos de Equivalência como Asunto , Humanos , Japão , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Índice de Gravidade de Doença , Ultrassonografia , Adulto Jovem
15.
Medicine (Baltimore) ; 99(32): e21480, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769882

RESUMO

BACKGROUND: The introduction of biological disease-modifying anti-rheumatic drugs into clinical practice has dramatically improved the clinical outcomes of individuals with rheumatoid arthritis (RA). We are conducting the IFX-SIRIUS STUDY I that evaluates whether switching from originator infliximab (IFX) to its biosimilar, CT-P13, is not inferior in maintaining nonclinical relapse to continue treatment with originator IFX in patients with RA achieving clinical remission. It is the next great issue whether disease activity can be maintained in good condition after discontinuation of CT-P13 because no evidence is available regarding the clinical value of discontinuing biosimilars in patients with RA. Thus, we will evaluate whether a condition without clinical relapse will be maintained after discontinuation of CT-P13 in patients with RA, achieving clinical remission or low disease activity during the IFX-SIRIUS STUDY I. METHODS/DESIGN: This study is an interventional, multicenter, open-label, single-arm clinical trial with a 48-week follow-up. Patients with RA who are treated with CT-P13 and sustained nonclinical relapse during the IFX-SIRIUS STUDY I will be included. Patients will discontinue CT-P13 after the study period of the IFX-SIRIUS STUDY I. We will evaluate disease activity by clinical disease activity indices and musculoskeletal ultrasound (MSUS). The primary endpoint is the proportion of patients who do not have clinical relapse during the study period. Important secondary endpoints are the changes from the baseline of the MSUS scores. We will also comprehensively analyze the serum levels of multiple biomarkers, such as cytokines and chemokines. In addition, if a clinical relapse occurs in patients after the discontinuation of CT-P13, we will evaluate the effectiveness and safety of restarting CT-P13. DISCUSSION: The study results are expected to show the clinical benefit of the discontinuation of CT-P13 and effectiveness and safety of restarting CT-P13 after clinical relapse. The strength of this study is to prospectively evaluate the therapeutic effectiveness by not only clinical disease activity indices but also standardized MSUS findings in multiple centers. We will explore whether parameters at baseline can predict a nonclinical relapse after the discontinuation of CT-P13 by integrating multilateral assessments, that is, patient's characteristics, clinical disease activity indices, MSUS findings, and serum biomarkers. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on April 20, 2020 as jRCTs071200007.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/patologia , Medicamentos Biossimilares/administração & dosagem , Substituição de Medicamentos , Infliximab/administração & dosagem , Adulto , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Biomarcadores/análise , Estudos de Equivalência como Asunto , Feminino , Humanos , Quimioterapia de Indução , Japão , Masculino , Recidiva , Resultado do Tratamento , Ultrassonografia
17.
BMJ ; 370: m2288, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32636183

RESUMO

OBJECTIVE: To assess the comparative effectiveness of biological medicines in rheumatoid arthritis in sufficiently similar patient populations, based on the current definitions of key outcomes. DESIGN: Systematic review and network meta-analysis including aggregate results from reanalysed individual patient data. DATA SOURCES: Clinical study reports and aggregate results from reanalyses of individual patient data on key outcomes for rheumatoid arthritis provided by study sponsors for studies conducted up to 2017, and several databases and registries from inception up to February 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials investigating patient relevant outcomes in adults with rheumatoid arthritis treated with biological medicines in combination with methotrexate after methotrexate failure for at least 24 weeks. RESULTS: 45 eligible trials were identified. Combining data from clinical study reports and aggregate results from reanalyses of individual patient data allowed extensive analyses yielding sufficiently similar populations and homogeneous study results for network meta-analyses, including up to 35 studies on eight biological medicines combined with methotrexate. These analyses showed few statistically significant differences between the combination treatments. For example, anakinra showed less benefit than almost all the other seven biological medicines regarding clinical remission or low disease activity (clinical disease activity index ≤2.8 or ≤10, respectively) and certolizumab pegol showed more harm than the other seven biological medicines regarding serious adverse events or infections. Some outcomes had very wide 95% confidence intervals, potentially implying unidentified differences between the eight biological medicines, but wide 95% confidence intervals were less prominent for low disease activity, serious adverse events, and infections. Owing to a lack of head-to-head trials, results were mainly based on indirect comparisons with a limited number of studies, and recently approved Janus kinase inhibitors could not be included. CONCLUSIONS: For patients with rheumatoid arthritis after methotrexate failure, only minor differences in benefits and harms were seen between biological medicines in combination with methotrexate. However, the analysis was hampered by a lack of long term direct comparisons. The substantial information gain achieved by the reanalysis of individual patient data calls for the routine availability of individual patient data.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Adulto , Progressão da Doença , Quimioterapia Combinada , Estudos de Equivalência como Asunto , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Indução de Remissão , Falha de Tratamento
18.
Trials ; 21(1): 609, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620144

RESUMO

OBJECTIVES: To evaluate the therapeutic effects of ultra-short-wave diathermy (SWD) on COVID-19 pneumonia. The hypothesis is that SWD may minimise pneumonic inflammation and shorten the duration of the time to positive-to-negative conversion of COVID-19 nucleic acid test. TRIAL DESIGN: This is a single centre, 2-arm (1:1 ratio), evaluator blinded, parallel group design superiority randomised, controlled clinical trial. PARTICIPANTS: The inclusion criteria were: (1) Age 18-65 years, (2) COVID-19 nucleic acid test is positive, (3) Lung CT showed multiple patchy ground glass shadows or other typical manifestations of both lungs. The exclusion criteria were: (1) Patients who need ICU management, (2) Positive tests for other pathogens such as Tuberculosis, Mycoplasma, (3) Patients with respiratory failure or requiring mechanical ventilation, (4) Patients with metal implants or pacemakers, (5) Those with shock (6) Those that have bleeding tendency or active bleeding in the lungs, (7) Patients with multiple organ failure who need ICU monitoring and treatment, (8) Cancer patients and those with severe underlying diseases, (9) Pregnant or lactating women, (10) Patients with severe cognitive impairment who cannot follow the instructions to complete the treatment, (11) Those without signed informed consent and (12) Those with other contraindications to short wave. This study will be conducted in Tongji Hospital, Caidian, Wuhan, People's Republic of China. INTERVENTION AND COMPARATOR: The experimental group will be given the nationally recommended standard medical treatment + ultra-short-wave diathermy treatment. Ultra-short-wave therapy treatment will be performed through application of ultra-short-wave therapy machine electrodes on the anterior and posterior parts of the trunk for 10 minutes, twice a day for 12 consecutive days. The comparator will be the control, not receiving ultra-short-wave therapy, and will be given only the nationally recommended standard medical treatment. MAIN OUTCOMES: The primary outcome measures will be time to positive-to-negative conversion of COVID-19 nucleic acid test by pharyngeal swab, in days assessed at 7th, 14th ,21st and 28th days. The secondary outcome measures include nucleic acid test rate and recovery from symptoms, Vital signs assessment, Computed Tomography, Complete blood count, serum analysis and SIRS scale scores. Blinded evaluation will be at baseline (the day of starting ultra-short-wave diathermy) and after 28 days following the interventions. RANDOMISATION: A Randomization plan will be generated online on www.randomization.com using permuted blocks method, by a statistician who will not be part of the study. Small blocks of various sizes will be used. Patients will be randomized (1:1) between the experimental and control groups BLINDING (MASKING): This will be an evaluator blinded study. Due to the nature of the intervention, blinding of patients and healthcare workers is not possible. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 410 patients will be randomised in 1:1 ratio to two groups: experimental group (n=205) and control group (n=205). TRIAL STATUS: Protocol version 1 was approved on 02/12/2020. Recruitment for this trial began on 02/18/2020 and will be ongoing till the required sample size is reached. The analysis deadline is August 2020. TRIAL REGISTRATION: This randomised controlled trial has been prospectively registered with the Chinese Clinical Trials ( ChiCTR2000029972 ) on 17 February 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol." The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Terapia por Ondas Curtas , Adolescente , Adulto , Idoso , China , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Estudos de Equivalência como Asunto , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Terapia por Ondas Curtas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
Trials ; 21(1): 610, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620174

RESUMO

OBJECTIVES: As there is no treatment for COVID-19 with a proven mortality benefit at this moment in the pandemic, supportive management including mechanical ventilation is the core management in an intensive care unit (ICU). It is a challenge to provide consistent care in this situation, highly demanding and leading to potential staff shortages in ICU. We need to reduce unnecessary exposure of healthcare workers to the virus. This study aims to examine the impact of care using a non-invasive oscillating device (NIOD) for chest physiotherapy in the care of mechanically ventilated patients with COVID-19. In particular, we aim to explore if a NIOD performed by non-specialized personnel is not inferior to the standard chest physiotherapy (CPT) undertaken by physiotherapists caring for patients with COVID-19. TRIAL DESIGN: A pilot multicenter prospective crossover noninferiority randomized controlled trial. PARTICIPANTS: All mechanically ventilated patients with COVID-19 admitted to one of the two ICUs, and CPT ordered by the responsible physician. The participants will be recruited from two intensive care units in Canadian Academic Hospitals (one pediatric and one adult ICU). INTERVENTION AND COMPARATOR: We will implement NIOD and CPT alternatingly for 3 h apart over 3 h. We will apply a pragmatic design, so that other procedures including hypertonic saline nebulization, intermittent positive pressure ventilation, suctioning (e.g., oral or nasal), or changing the ventilator settings or modality (i.e., increasing positive end-expiratory pressure or changing the nasal mask to total face continuous positive airway pressure) can be provided at the direction of bedside intensivists in charge. MAIN OUTCOMES: The primary outcome measurement is the oxygenation level before and after the procedure (SpO2/FiO2 ratio). For cases with invasive ventilation (i.e., the use of an endotracheal tube to deliver positive pressure) and non-invasive ventilation, we will also document expiratory tidal volume, vital signs, and any related complications such as vomiting, hypoxemia, or unexpected extubation. We will collect the data before, 10 min after, and 30 min after the procedure. RANDOMIZATION: The order of the procedures (i.e., NIOD or CPT) will be randomly allocated using manual generated random numbers for each case. Randomization will be carried out by the independent research assistant in the study coordinating center by using opaque sealed envelopes, assigning an equal number of cases to each intervention arm. Stratification will be applied for age (> 18 years or ≤ 18 years of age) and the study sites. BLINDING (MASKING): No blinding will be performed. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): We estimate the necessary sample size as 25 for each arm (total 50 cases), with a power of 0.90 and an alpha of 0.05, with a non-inferiority design. TRIAL STATUS: The protocol version number 1 was approved on 27 March 2020. Currently, recruitment has not yet started, with the start scheduled by the mid-June 2020 and the end anticipated by December 2020. TRIAL REGISTRATION: ClinicalTrials.gov NCT04361435 . Registered on 28 April 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional File 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/terapia , Pulmão/virologia , Modalidades de Fisioterapia , Pneumonia Viral/terapia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Estado Terminal , Estudos de Equivalência como Asunto , Interações Hospedeiro-Patógeno , Humanos , Pulmão/fisiopatologia , Estudos Multicêntricos como Assunto , Pandemias , Modalidades de Fisioterapia/efeitos adversos , Modalidades de Fisioterapia/instrumentação , Projetos Piloto , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Estudos Prospectivos , Quebeque , Respiração Artificial , Fatores de Tempo , Resultado do Tratamento
20.
Am Heart J ; 227: 40-46, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32673830

RESUMO

BACKGROUND: The optimal antibiotic treatment length for infective endocarditis (IE) is uncertain. International guidelines recommend treatment duration of up to 6 weeks for patients with left-sided IE but are primarily based on historical data and expert opinion. Efficacies of modern therapies, fast recovery seen in many patients with IE, and complications to long hospital stays challenge the rationale for fixed treatment durations in all patients. OBJECTIVE: The objective was to conduct a noninferiority randomized controlled trial (acronym POET II) investigating the safety of accelerated (shortened) antibiotic therapy as compared to standard duration in patients with left-sided IE. METHODS: The POET II trial is a multicenter, multinational, open-label, noninferiority randomized controlled trial. Patients with definite left-sided IE due to Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis will be eligible for enrolment. Each patient will be randomized to accelerated antibiotic treatment or standard-length treatment (1:1) following clinical stabilization as defined by clinical parameters, laboratory values, and transesophageal echocardiography findings. Accelerated treatment will be between 2 and 4 weeks, whereas standard-length treatment will be between 4 and 6 weeks, depending on microbiologic etiology, complications, need for valve surgery, and prosthetic versus native valve endocarditis. The primary outcome is a composite of all-cause mortality, unplanned cardiac surgery, relapse of bacteremia, or embolization within 6 months of randomization. CONCLUSIONS: The POET II trial will investigate the safety of accelerated antibiotic therapy for patients with left-sided IE caused by Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis. The results of the POET II trial will improve the evidence base of treatment recommendations, and clinical practice may be altered.


Assuntos
Antibacterianos/administração & dosagem , Endocardite Bacteriana/tratamento farmacológico , Enterococcus faecalis , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Infecções Estreptocócicas/tratamento farmacológico , Estudos de Equivalência como Asunto , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Estudos Multicêntricos como Assunto , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...