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1.
Medicine (Baltimore) ; 100(3): e24103, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33546016

RESUMEN

OBJECTIVE: Currently, it is unclear whether the salviae miltiorrhizae (Danshen Salvia) and ligustrazine hydrochloride (Chuanxiong Chuanxiong) (SMLH) injection combined with mecobalamin can improve diabetic peripheral neuropathy (DPN). We conducted a systematic analysis to evaluate the clinical effects of SMLH injection combined with mecobalamin for treating DPN. METHODS: Seven databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wang Fang), Chinese Biomedical Literature Database (CBM), and VIP Database for Chinese Technical Periodicals (VIP) were searched for systematic literature retrieval. Each database was searched up to 2020 to identify randomized controlled trials on DPN treated with SMLH injection combined with mecobalamin. We used the RevMan 5.3 and Stata 14.0 software to assess the risk of bias in the included trials. RESULTS: A total of 15 publications, including 1349 samples, were reviewed. The total effective rate of SMLH injection combined with mecobalamin was 31% higher than that of mecobalamin alone (95% confidence interval [CI] = 1.23-1.38; P < .00001). The experimental group showed a significant increase in the motor conduction velocity (MCV) of the peroneal nerve (weighted mean difference [WMD] = 4.81, 95% CI 3.53-6.09; P < .00001). In addition, SMLH injection combined with mecobalamin showed a statistical significant effect on the sensory conduction velocity (SCV) of the peroneal nerve (WMD = 5.03, 95% CI = 4.16-5.90; P < .00001), and MCV of the median nerve (WMD = 5.38, 95% CI = 4.05-6.72; P < .00001). The WMD for the change in SCV in the median nerve was 4.89 m/s (95% CI = 3.88-5.89; P < .00001). The P-values of the Egger and Begg tests were 0.967 and 0.961, respectively, indicating no publication bias. Subgroup and sensitivity analyses indicated that the results for MCV and SCV of the peroneal nerve and the median nerve were stable. CONCLUSION: SMLH injection combined with mecobalamin can improve DPN, compared with mecobalamin alone.


Asunto(s)
Neuropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Fitoterapia , Pirazinas/uso terapéutico , Salvia miltiorrhiza , Medicamentos Herbarios Chinos/farmacología , Humanos , Inyecciones , Conducción Nerviosa/efectos de los fármacos , Pirazinas/farmacología , Vitamina B 12/análogos & derivados , Vitamina B 12/uso terapéutico
2.
Trials ; 22(1): 59, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33451350

RESUMEN

BACKGROUND: Several drugs are being repurposed for the treatment of the coronavirus disease 2019 (COVID-19) pandemic based on in vitro or early clinical findings. As these drugs are being used in varied regimens and dosages, it is important to enable synthesis of existing safety data from clinical trials. However, availability of safety information is limited by a lack of timely reporting of overall clinical trial results on public registries or through academic publication. We aimed to analyse the evidence gap in this data by conducting a rapid review of results posting on ClinicalTrials.gov and in academic publications to quantify the number of trials missing results for drugs potentially being repurposed for COVID-19. METHODS: ClinicalTrials.gov was searched for 19 drugs that have been identified as potential treatments for COVID-19. Relevant clinical trials for any prior indication were listed by identifier (NCT number) and checked for results and for timely result reporting (within 395 days of the primary completion date). Additionally, PubMed and Google Scholar were searched to identify publications of results not listed on the registry. A second, blinded search of 10% of trials was conducted to assess reviewer concordance. RESULTS: Of 3754 completed trials, 1516 (40.4%) did not post results on ClinicalTrials.gov or in the academic literature. Tabular results were available on ClinicalTrials.gov for 1172 (31.2%) completed trials. A further 1066 (28.4%) had published results in the academic literature, but did not report results on ClinicalTrials.gov . Key drugs missing clinical trial results include hydroxychloroquine (37.0% completed trials unreported), favipiravir (77.8%) and lopinavir (40.5%). CONCLUSIONS: There is an important evidence gap for the safety of drugs being repurposed for COVID-19. This uncertainty could cause unnecessary additional morbidity and mortality during the pandemic. We recommend caution in experimental drug use for non-severe disease and urge clinical trial sponsors to report missing results retrospectively.


Asunto(s)
Antivirales/uso terapéutico , Ensayos Clínicos como Asunto , Inhibidores Enzimáticos/uso terapéutico , Sistema de Registros , Informe de Investigación , Amidas/uso terapéutico , Combinación de Medicamentos , Reposicionamiento de Medicamentos , Medicina Basada en la Evidencia , Humanos , Hidroxicloroquina/uso terapéutico , Lopinavir/uso terapéutico , PubMed , Pirazinas/uso terapéutico , Proyectos de Investigación , Ritonavir/uso terapéutico
3.
J Hematol Oncol ; 14(1): 15, 2021 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-33441177

RESUMEN

Bruton's tyrosine kinase (BTK) inhibitors, drugs utilized in cancer, are being repurposed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (COVID-19). Recently, BTK inhibitors acalabrutinib and ibrutinib have been found to protect against pulmonary injury in a small group of patients infected with SARS-CoV-2. The high levels of pro-inflammatory cytokines found in the circulation of COVID-19 patients with severe lung disease suggest the involvement of the innate immune system in this process. Understanding the potential mechanism of action of BTK inhibition in SARS-CoV-2 is clearly of importance to determine how acalabrutinib, ibrutinib and possibly other BTK inhibitors may provide protection against lung injury.


Asunto(s)
Adenina/análogos & derivados , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Benzamidas/uso terapéutico , Piperidinas/uso terapéutico , Pirazinas/uso terapéutico , Adenina/uso terapéutico , Citocinas/genética , Citocinas/metabolismo , Reposicionamiento de Medicamentos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos
4.
Arch Virol ; 166(3): 949-954, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33492523

RESUMEN

No specific antiviral drugs have been approved for the treatment of COVID-19. This study aimed to evaluate the efficacy of favipiravir in treatment of COVID-19. This was a multicenter randomized controlled study including 96 patients with COVID- 19 who were randomly assigned into a chloroquine (CQ) group and a favipiravir group. None of the patients in the favipiravir group needed mechanical ventilation (p = 0.129). One patient (2.3%) in the favipiravir group and two patients (4.2%) in the CQ group died (p = 1.00). Favipiravir is a promising drug for COVID-19 that decreases the hospital stay and the need for mechanical ventilation.ClinicalTrials.gov Identifier NCT04351295.


Asunto(s)
Amidas/uso terapéutico , Antivirales/uso terapéutico , Pirazinas/uso terapéutico , /efectos de los fármacos , Adulto , Cloroquina/uso terapéutico , Femenino , Humanos , Tiempo de Internación , Masculino , Respiración Artificial/estadística & datos numéricos , Resultado del Tratamiento
6.
Ann Palliat Med ; 10(1): 707-720, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33440983

RESUMEN

The whole world is battling through coronavirus disease 2019 (COVID-19) which is a fatal pandemic. In the early 2020, the World Health Organization (WHO) declared it as a global health emergency without definitive treatments and preventive approaches. In the absence of definitive therapeutic agents, this thorough review summarizes and outlines the potency and safety of all molecules and therapeutics which may have potential antiviral effects. A number of molecules and therapeutics licensed or being tested for some other conditions were found effective in different in vitro studies as well as in many small sample-sized clinical trials and independent case studies. However, in those clinical trials, there were some limitations which need to be overcome to find the most promising antiviral against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In conclusion, many of above-mentioned antivirals seems to have some therapeutic effects but none of them have been shown to have a strong evidence for their proper recommendation and approval in the treatment of COVID-19. Constantly evolving new evidences, exclusive adult data, language barrier, and type of study (observational, retrospective, small-sized clinical trials, or independent case series) resulted to the several limitations of this review. The need for multicentered, large sample-sized, randomized, placebo-controlled trials on COVID-19 patients to reach a proper conclusion on the most promising antiviral agent is warranted.


Asunto(s)
Antivirales/uso terapéutico , /terapia , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/farmacología , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/farmacología , Alanina/uso terapéutico , Amidas/farmacología , Amidas/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Azetidinas/farmacología , Azetidinas/uso terapéutico , Cloroquina/farmacología , Cloroquina/uso terapéutico , Combinación de Medicamentos , Humanos , Hidroxicloroquina/farmacología , Hidroxicloroquina/uso terapéutico , Inmunización Pasiva , Indoles/farmacología , Indoles/uso terapéutico , Interferones/farmacología , Interferones/uso terapéutico , Ivermectina/farmacología , Ivermectina/uso terapéutico , Lopinavir/farmacología , Lopinavir/uso terapéutico , Oseltamivir/farmacología , Oseltamivir/uso terapéutico , Purinas/farmacología , Purinas/uso terapéutico , Pirazinas/farmacología , Pirazinas/uso terapéutico , Pirazoles/farmacología , Pirazoles/uso terapéutico , Ribavirina/farmacología , Ribavirina/uso terapéutico , Ritonavir/farmacología , Ritonavir/uso terapéutico , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Tiazoles/farmacología , Tiazoles/uso terapéutico
7.
Intern Med ; 60(1): 123-130, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33390469

RESUMEN

Case 1: A 65-year-old man with novel coronavirus infection (COVID-19) complicated with acute respiratory failure. On admission, the patient was started on favipiravir and corticosteroid. However, due to a lack of significant improvement, he was introduced to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Although iliopsoas hematoma occurred as a complication, the patient recovered. Case 2: A 49-year-old man with COVID-19 had been started on favipiravir and corticosteroid. Due to progressive respiratory failure, the patient underwent mechanical ventilation and ECMO. The patient recovered without complications. We successfully treated these severe cases with a multimodal combination of pharmacological and non-pharmacological supportive therapy.


Asunto(s)
Corticoesteroides/uso terapéutico , Amidas/uso terapéutico , Antivirales/uso terapéutico , Oxigenación por Membrana Extracorpórea , Metilprednisolona/uso terapéutico , Pirazinas/uso terapéutico , Respiración Artificial , Anciano , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/virología
8.
J Infect Chemother ; 27(2): 390-392, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33402301

RESUMEN

Favipiravir is an antiviral drug that is expected to have a therapeutic effect on SARS-CoV2 infection. Teratogenicity and hyperuricemia are known as the main side effects of favipiravir, but little is known about other side effects. This report describes a case of cholestatic liver injury induced by favipiravir. A 73-year-old Japanese with a history of alcoholic hepatitis was infected with SARS-CoV2. Drug therapy was instituted with lopinavir/ritonavir combined with interferon ß-1b. However, his condition worsened despite additional support with continuous hemodiafiltration and veno-venous extracorporeal membrane oxygenation. We suspected complications of bacterial pneumonia and started favipiravir in addition to antimicrobial therapy. Favipiravir was administered at 6000 mg/day on the first day and 2400 mg/day for the second and subsequent days for 14 days. After the initiation of antibiotics, transaminase and total bilirubin were elevated, suggesting a transient cholestasic liver dysfunction. The liver dysfunction in this case may have been triggered by antibacterial treatment, and high dose of favipiravir may have promoted the deterioration of liver function. Monitoring of liver function is vital and close attention should be paid when using favipiravir at high doses or in patients with impaired liver function.


Asunto(s)
Amidas/efectos adversos , Antivirales/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Colestasis/etiología , Pirazinas/efectos adversos , Anciano , Amidas/uso terapéutico , Antivirales/uso terapéutico , Quimioterapia Combinada , Oxigenación por Membrana Extracorpórea , Humanos , Lopinavir/uso terapéutico , Masculino , Pirazinas/uso terapéutico , Ritonavir/uso terapéutico
9.
Biomed Pharmacother ; 133: 110825, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33378989

RESUMEN

BACKGROUND: Since December 2019, COVID-19 has spread to almost every corner of the world. In theory, tocilizumab and favipiravir are considered to be reliable drugs for the treatment of COVID-19 with elevated IL-6. We aimed to assess the efficacy and safety of tocilizumab combined with favipiravir in patients with COVID-19. METHODS: This was a multicenter trial in adults with COVID-19. Patients were randomly assigned (3:1:1) to a 14-day combination of favipiravir combined with tocilizumab (combination group), favipiravir, and tocilizumab. The primary outcome was the cumulative lung lesion remission rate (lung CT examination indicated absorption of lung inflammation). RESULTS: Between Feb 2 and March 15, 2020, 26 patients were recruited; 14 were randomly assigned to the combination group, 7 were assigned to the favipiravir group and 5 were assigned to the tocilizumab group. The cumulative lung lesion remission rate at day 14 was significantly higher in combination group as compared with favipiravir group (P = 0.019, HR 2.66 95 % CI [1.08-6.53]). And there was also a significant difference between tocilizumab and favipivavir (P = 0.034, HR 3.16, 95 % CI 0.62-16.10). In addition, there was no significant difference between the combination group and the tocilizumab group (P = 0.575, HR 1.28 95 %CI 0.39-4.23). Furthermore, combined therapy can also significantly relieve clinical symptoms and help blood routine to return to normal. No serious adverse events were reported. CONCLUSION: Tocilizumab combined with or without favipiravir can effectively improve the pulmonary inflammation of COVID-19 patients and inhibit the deterioration of the disease.


Asunto(s)
Amidas/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Pirazinas/uso terapéutico , /efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Amidas/administración & dosificación , Amidas/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Antivirales/administración & dosificación , Antivirales/efectos adversos , /patología , Quimioterapia Combinada , Femenino , Humanos , Interleucina-6/sangre , Estimación de Kaplan-Meier , Pulmón/diagnóstico por imagen , Pulmón/patología , Masculino , Persona de Mediana Edad , Modelos Inmunológicos , Pirazinas/administración & dosificación , Pirazinas/efectos adversos , Receptores de Interleucina-6/antagonistas & inhibidores , Respiración Artificial/estadística & datos numéricos , Tamaño de la Muestra , Resultado del Tratamiento
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 249: 119241, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33333412

RESUMEN

The present work describes development of rapid, robust, sensitive and green spectrofluorimetric method for determination of favipiravir (FAV). Different factors affecting fluorescence were carefully studied and Box Behnken Design was applied to optimize experimental parameters. The proposed method is based on measuring native fluorescence of FAV in 0.2 M borate buffer (pH 8.0) at 432 nm after excitation at 361 nm. There was a linear relationship between FAV concentration and relative fluorescence intensity over the range 40-280 ng/mL with limit of detection of 9.44 ng/mL and quantitation limit of 28.60 ng/mL. The method was successfully implemented for determination of FAV in its pharmaceutical formulation with mean % recovery of 99.26 ± 0.87. Moreover, the high sensitivity of the method allowed determination of FAV in spiked human plasma over a range of 48-192 ng/mL. The proposed spectrofluorimetric method was proved to be eco-friendly according to analytical eco-scale.


Asunto(s)
Amidas/sangre , Antivirales/sangre , /tratamiento farmacológico , Pirazinas/sangre , Espectrometría de Fluorescencia/métodos , Amidas/análisis , Amidas/uso terapéutico , Antivirales/análisis , Antivirales/uso terapéutico , Análisis Químico de la Sangre/métodos , Análisis Químico de la Sangre/estadística & datos numéricos , Humanos , Límite de Detección , Pirazinas/análisis , Pirazinas/uso terapéutico , Sensibilidad y Especificidad , Espectrometría de Fluorescencia/estadística & datos numéricos
11.
Eur Rev Med Pharmacol Sci ; 24(23): 12593-12608, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33336780

RESUMEN

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly increasing but the medication options are still limited for this perilous disease. The emergent outbreak of COVID-19 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps propagating globally. The present scenario has emphasized the requirement for therapeutic opportunities to relive and overcome this latest pandemic. Despite the fact, the deteriorating developments of COVID-19, there is no drug certified to have considerable effects in the medical treatment for COVID-19 patients. The COVID-19 pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can save the lives of seriously ill patients, and it is shown in a randomized clinical trial by the United Kingdom that it reduced the death rate in COVID-19 patients. The current review recapitulates the existing evidence of possible therapeutic drugs, peptides, humanized antibodies, convulsant plasma, and vaccination that has revealed potential in fighting COVID-19 infections. Many randomized and controlled clinical trials are taking place to further validate these agent's safety and effectiveness in curing COVID-19.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antivirales/uso terapéutico , /tratamiento farmacológico , /terapia , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Amidas/uso terapéutico , Antibacterianos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Neutralizantes/uso terapéutico , Antiparasitarios/uso terapéutico , Cannabinoides/uso terapéutico , Cloroquina/uso terapéutico , Inactivadores del Complemento/uso terapéutico , Dexametasona/uso terapéutico , Combinación de Medicamentos , Inhibidores Enzimáticos/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Inmunización Pasiva , Indoles/uso terapéutico , Interferones/uso terapéutico , Ivermectina/uso terapéutico , Lopinavir/uso terapéutico , Pirazinas/uso terapéutico , Ritonavir/uso terapéutico , Teicoplanina/uso terapéutico , Tetraciclinas/uso terapéutico , Tiazoles/uso terapéutico
12.
Adv Chronic Kidney Dis ; 27(5): 434-441, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-33308510

RESUMEN

Coronavirus disease 2019, the disease caused by the severe acute respiratory syndrome coronavirus 2 virus, was first identified in the Hubei Province of China in late 2019. Currently, the only role for therapy is treatment of the disease, as opposed to postexposure prophylaxis, however multiple clinical trials are currently ongoing for both treatment and prophylaxis. Treating coronavirus disease 2019 relies on two components; the first is inhibition of the viral entrance and replication within the body and the second is inhibition of an exacerbated immune response which can be seen in patients with severe disease. Many drugs have shown in vitro antiviral activity; however, clinical trials have not been as promising. This review summarizes the current data for the most commonly used drugs for coronavirus disease 2019 and will cover the unique factors that may affect the dosing of these medications in patients with CKD. While clinical trials are ongoing, most are in patients with normal kidney function. During a pandemic, when patients with CKD are at higher risk of both infection and death, it is imperative to include patients these patients in the clinical trials.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antivirales/uso terapéutico , Insuficiencia Renal Crónica/metabolismo , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Amidas/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , /prevención & control , /uso terapéutico , Cloroquina/uso terapéutico , Creatinina/metabolismo , Citidina/análogos & derivados , Citidina/uso terapéutico , Dexametasona/uso terapéutico , Combinación de Medicamentos , Interacciones Farmacológicas , Humanos , Hidroxicloroquina/uso terapéutico , Hidroxilaminas/uso terapéutico , Inmunización Pasiva , Interferones/uso terapéutico , Inhibidores de las Cinasas Janus/uso terapéutico , Lopinavir/uso terapéutico , Pirazinas/uso terapéutico , Eliminación Renal , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Terapia de Reemplazo Renal , Ribavirina/uso terapéutico , Ritonavir/uso terapéutico
13.
Intern Med ; 59(22): 2951-2953, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33191372

RESUMEN

We herein report the first case of a fever induced by favipiravir, a potential coronavirus disease 2019 therapeutic drug. An 82-year-old man diagnosed with bilateral pneumonia was transferred to our hospital following a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test. He was treated with compassionate use of favipiravir. Both his oxygen demand and fever gradually improved after admission; however, his fever relapsed, and the C-reactive protein (CRP) levels increased on day 7. We diagnosed his fever as being favipiravir-induced. The fever resolved a few days after favipiravir discontinuation, demonstrating the accuracy of the diagnosis. This case revealed that favipiravir can induce a fever.


Asunto(s)
Amidas/efectos adversos , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Fiebre/inducido químicamente , Neumonía Viral/tratamiento farmacológico , Pirazinas/efectos adversos , Anciano de 80 o más Años , Amidas/uso terapéutico , Antivirales/efectos adversos , Antivirales/uso terapéutico , Infecciones por Coronavirus/epidemiología , Humanos , Masculino , Pandemias , Neumonía Viral/epidemiología , Pirazinas/uso terapéutico
14.
Trials ; 21(1): 935, 2020 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-33213530

RESUMEN

OBJECTIVES: The GETAFIX trial will test the hypothesis that favipiravir is a more effective treatment for COVID-19 infection in patients who have early stage disease, compared to current standard of care. This study will also provide an important opportunity to investigate the safety and tolerability of favipiravir, the pharmacokinetic and pharmacodynamic profile of this drug and mechanisms of resistance in the context of COVID-19 infection, as well as the effect of favipiravir on hospitalisation duration and the post COVID-19 health and psycho-social wellbeing of patients recruited to the study. TRIAL DESIGN: GETAFIX is an open label, parallel group, two arm phase II/III randomised trial with 1:1 treatment allocation ratio. Patients will be randomised to one of two arms and the primary endpoint will assess the superiority of favipiravir plus standard treatment compared to standard treatment alone. PARTICIPANTS: This trial will recruit adult patients with confirmed positive valid COVID-19 test, who are not pregnant or breastfeeding and have no prior major co-morbidities. This is a multi-centre trial, patients will be recruited from in-patients and outpatients from three Glasgow hospitals: Royal Alexandra Hospital; Queen Elizabeth University Hospital; and the Glasgow Royal Infirmary. Patients must meet all of the following criteria: 1. Age 16 or over at time of consent 2. Exhibiting symptoms associated with COVID-19 3. Positive for SARS-CoV-2 on valid COVID-19 test 4. Point 1, 2, 3, or 4 on the WHO COVID-19 ordinal severity scale at time of randomisation. (Asymptomatic with positive valid COVID-19 test, Symptomatic Independent, Symptomatic assistance needed, Hospitalized, with no oxygen therapy) 5. Have >=10% risk of death should they be admitted to hospital as defined by the ISARIC4C risk index: https://isaric4c.net/risk 6. Able to provide written informed consent 7. Negative pregnancy test (women of childbearing potential*) 8. Able to swallow oral medication Patients will be excluded from the trial if they meet any of the following criteria: 1. Renal impairment requiring, or likely to require, dialysis or haemofiltration 2. Pregnant or breastfeeding 3. Of child bearing potential (women), or with female partners of child bearing potential (men) who do not agree to use adequate contraceptive measures for the duration of the study and for 3 months after the completion of study treatment 4. History of hereditary xanthinuria 5. Other patients judged unsuitable by the Principal Investigator or sub-Investigator 6. Known hypersensitivity to favipiravir, its metabolites or any excipients 7. Severe co-morbidities including: patients with severe hepatic impairment, defined as: • greater than Child-Pugh grade A • AST or ALT > 5 x ULN • AST or ALT >3 x ULN and Total Bilirubin > 2xULN 8. More than 96 hours since first positive COVID-19 test sample was taken 9. Unable to discontinue contra-indicated concomitant medications This is a multi-centre trial, patients will be recruited from in-patients and outpatients from three Glasgow hospitals: Royal Alexandra Hospital; Queen Elizabeth University Hospital; and the Glasgow Royal Infirmary. INTERVENTION AND COMPARATOR: Patients randomised to the experimental arm of GETAFIX will receive standard treatment for COVID-19 at the discretion of the treating clinician plus favipiravir. These patients will receive a loading dose of favipiravir on day 1 of 3600mg (1800mg 12 hours apart). On days 2-10, patients in the experimental arm will receive a maintenance dose of favipiravir of 800mg 12 hours apart (total of 18 doses). Patients randomised to the control arm of the GETAFIX trial will receive standard treatment for COVID-19 at the discretion of the treating clinician. MAIN OUTCOMES: The primary outcome being assessed in the GETAFIX trial is the efficacy of favipiravir in addition to standard treatment in patients with COVID-19 in reducing the severity of disease compared to standard treatment alone. Disease severity will be assessed using WHO COVID 10 point ordinal severity scale at day 15 +/- 48 hours. All randomised participants will be followed up until death or 60 days post-randomisation (whichever is sooner). RANDOMISATION: Patients will be randomised 1:1 to the experimental versus control arm using computer generated random sequence allocation. A minimisation algorithm incorporating a random component will be used to allocate patients. The factors used in the minimisation will be: site, age (16-50/51-70/71+), history of hypertension or currently obsess (BMI>30 or obesity clinically evident; yes/no), 7 days duration of symptoms (yes/no/unknown), sex (male/female), WHO COVID-19 ordinal severity score at baseline (1/2or 3/4). BLINDING (MASKING): No blinding will be used in the GETAFIX trial. Both participants and those assessing outcomes will be aware of treatment allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): In total, 302 patients will be randomised to the GETAFIX trial: 151 to the control arm and 151 to the experimental arm. There will be an optional consent form for patients who may want to contribute to more frequent PK and PD sampling. The maximum number of patients who will undergo this testing will be sixteen, eight males and eight females. This option will be offered to all patients who are being treated in hospital at the time of taking informed consent, however only patients in the experimental arm of the trial will be able to undergo this testing. TRIAL STATUS: The current GETAFIX protocol is version 4.0 12th September 2020. GETAFIX opened to recruitment on 26th October 2020 and will recruit patients over a period of approximately six months. TRIAL REGISTRATION: GETAFIX was registered on the European Union Drug Regulating Authorities Clinical Trials (EudraCT) Database on 15th April 2020; Reference number 2020-001904-41 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001904-41/GB ). GETAFIX was registered on ISRCTN on 7th September 2020; Reference number ISRCTN31062548 ( https://www.isrctn.com/ISRCTN31062548 ). 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 (see Additional file 2).


Asunto(s)
Amidas/uso terapéutico , Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Pirazinas/uso terapéutico , Adulto , Amidas/administración & dosificación , Amidas/farmacocinética , Amidas/farmacología , Antivirales/administración & dosificación , Antivirales/farmacocinética , Antivirales/farmacología , Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , Estudios de Casos y Controles , Infecciones por Coronavirus/clasificación , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Femenino , Hospitalización , Humanos , Masculino , Pandemias/clasificación , Neumonía Viral/clasificación , Neumonía Viral/epidemiología , Neumonía Viral/virología , Pirazinas/administración & dosificación , Pirazinas/farmacocinética , Pirazinas/farmacología , Seguridad , Escocia/epidemiología , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
15.
Trials ; 21(1): 904, 2020 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-33129363

RESUMEN

OBJECTIVES: The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychloroquine in SARS-CoV-2. The two medications were listed in many guidelines as treatment options and ongoing trials assessing their efficacy and safety. Thus, we want to prove the clinical effectiveness of the combination as therapy. TRIAL DESIGN: This is an Open label, multicenter, randomized controlled clinical trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. It is a multicenter trial that will compare Favipiravir plus Hydroxychloroquine combination (experimental arm) to a control arm. PARTICIPANTS: All study procedures will be conducted in eight centres in Saudia Arabia: King Abdulaziz Medical City National Guard Health Affairs in Riyadh. King Abdulaziz Hospital - Al Ahsa, Saudi Arabia AlMadina General Hospital, Madnia, Saudi Arabia Al-Qatif Central Hospital, Saudi Arabia Imam Abdulrahman Al Faisal Hospital, Dammam, Saudi Arabia King Abdulaziz Medical City, Jeddah, Saudi Arabia King Abdulaziz Hospital, Makkah, Saudi Arabia Imam Abdulrahman Alfaisal Hospital, Riyadh, Saudi Arabia Inclusion Criteria • Should be at least 18 years of age, • Male or nonpregnant female, • Diagnosed with COVID-19 by PCR confirmed SARS-coV-2 viral infection. • Able to sign the consent form and agree to clinical samples collection (or their legal surrogates if subjects are or become unable to make informed decisions).. • Moderate or Severe COVID-19, defined as oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or significant clinical symptoms that require hospital admission. • patients had to be enrolled within 10 days of disease onset. Exclusion Criteria • Patients who are pregnant or breastfeeding. • Will be transferred to a non-study site hospital or discharged from hospital within 72 hours. • Known sensitivity/allergy to hydroxychloroquine or Favipiravir • Current use of hydroxychloroquine for another indication • Prior diagnosis of retinopathy • Prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency • Major comorbidities increasing the risk of study drug including: i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy, iii. Known history of ventricular arrhythmias, iv. Current use of drugs that prolong the QT interval, Severe liver damage (Child-Pugh score ≥ C, AST> 5 times the upper limit), HIV. • The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues). • Clinical prognostic non-survival, palliative care, or in deep coma and no have response to supportive treatment within three hours of admission • Patient with irregular rhythm • Patient with a history of heart attack (myocardial infarction) • Patient with a family history of sudden death from heart attack before the age of 50 • Take other drugs that can cause prolonged QT interval • Patient who is receiving immunosuppressive therapy (cyclosporin) which cannot be switched to another agent or adjusted while using the investigational drug • Gout/history of Gout or hyperuricemia (above the ULN), hereditary xanthinuria or xanthine calculi of the urinary tract. INTERVENTION AND COMPARATOR: The treatment intervention would be for a maximum of 10 days from randomization and it would be as follows: Favipiravir for 10 days: Administer 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (total days of therapy is 10 days) Hydroxychloroquine for 5 days: (400mg) twice daily on day 1; for days 2-5 (200mg) twice daily. Reference Comparator Therapy: Standard of care is defined as: Treatment that is accepted by medical experts as a proper treatment for Covid-19 disease. Standard care comprised of, as necessary, supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, extracorporeal membrane oxygenation (ECMO), and antiviral therapy except Favipiravir. Also, it may include intravenous fluids and medications for symptoms relief . MAIN OUTCOMES: The primary endpoint is the time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first (14 days from Randomization). RANDOMISATION: Eligible participants will be randomized in a 1:1 ratio to either the combination group (Favipiravir and Hydroxychloroquine) or a control group. The patients will be randomized utilizing Web based data entry System with a stratification based on the centre and the ICU admission. BLINDING (MASKING): This is an Open label study and only the analyst will be blinded during the study conduct. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Under the classical two arm parallel design the total effective sample sizes needed is 472 subjects (236 subjects per group). TRIAL STATUS: Protocol version 3.1 (dated 11 Aug 2020), and currently recruitment is ongoing. The date recruitment started was May 21, 2020 and the investigators anticipate the trial will finish recruiting by the end of December 2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04392973 , 19 May 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.


Asunto(s)
Amidas/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Pirazinas/uso terapéutico , Amidas/efectos adversos , Antivirales/efectos adversos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Quimioterapia Combinada , Femenino , Interacciones Huésped-Patógeno , Humanos , Hidroxicloroquina/efectos adversos , Pacientes Internos , Masculino , Estudios Multicéntricos como Asunto , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Pirazinas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Arabia Saudita , Factores de Tiempo , Resultado del Tratamiento
16.
Trials ; 21(1): 846, 2020 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-33050924

RESUMEN

OBJECTIVES: To assess the efficacy of several repurposed drugs to prevent hospitalisation or death in patients aged 65 or more with recent symptomatic SARS-CoV-2 infection (COVID-19) and no criteria for hospitalisation. TRIAL DESIGN: Phase III, multi-arm (5) and multi-stage (MAMS), randomized, open-label controlled superiority trial. Participants will be randomly allocated 1:1:1:1:1 to the following strategies: Arm 1: Control arm Arms 2 to 5: Experimental treatment arms Planned interim analyses will be conducted at regular intervals. Their results will be reviewed by an Independent Data and Safety Monitoring Board. Experimental arms may be terminated for futility, efficacy or toxicity before the end of the trial. New experimental arms may be added if new evidence suggests that other treatments should be tested. A feasibility and acceptability substudy as well as an immunological substudy will be conducted alongside the trial. PARTICIPANTS: Inclusion criteria are: 65-year-old or more; Positive test for SARS-CoV-2 on a nasopharyngeal swab; Symptoms onset within 3 days before diagnosis; No hospitalisation criteria; Signed informed consent; Health insurance. Exclusion criteria are: Inability to make an informed decision to participate (e.g.: dementia, guardianship); Rockwood Clinical Frailty Scale ≥7; Long QT syndrome; QTc interval > 500 ms; Heart rate <50/min; Kalaemia >5.5 mmol/L or <3.5 mmol/L; Ongoing treatment with piperaquine, halofantrine, dasatinib, nilotinib, hydroxyzine, domperidone, citalopram, escitalopram, potent inhibitors or inducers of cytochrome P450 CYP3A4 isoenzyme, repaglinide, azathioprine, 6-mercaptopurine, theophylline, pyrazinamide, warfarin; Known hypersensitivity to any of the trial drugs or to chloroquine and other 4-aminoquinolines, amodiaquine, mefloquine, glafenine, floctafenine, antrafenine, ARB; Hepatic porphyria; Liver failure (Child-Pugh stage ≥B); Stage 4 or 5 chronic kidney disease (GFR <30 mL/min/1.73 m²); Dialysis; Hypersentivity to lactose; Lactase deficiency; Abnormalities in galactose metabolism; Malabsorption syndrome; Glucose-6-phosphate dehydrogenase deficiency; Symptomatic hyperuricemia; Ileus; Colitis; Enterocolitis; Chronic hepatitis B virus disease. The trial is being conducted in France in the Bordeaux, Corse, Dijon, Nancy, Paris and Toulouse areas as well as in the Grand Duchy of Luxembourg. Participants are recruited either at home, nursing homes, general practices, primary care centres or hospital outpatient consultations. INTERVENTION AND COMPARATOR: The four experimental treatments planned in protocol version 1.2 (April 8th, 2020) are: (1) Hydroxychloroquine 200 mg, 2 tablets BID on day 0, 2 tablets QD from day 1 to 9; (2) Imatinib 400 mg, 1 tablet QD from day 0 to 9; (3) Favipiravir 200 mg, 12 tablets BID on day 0, 6 tablets BID from day 1 to 9; (4) Telmisartan 20 mg, 1 tablet QD from day 0 to 9. The comparator is a complex of vitamins and trace elements (AZINC Forme et Vitalité®), 1 capsule BID for 10 days, for which there is no reason to believe that they are active on the virus. In protocol version 1.2 (April 8th, 2020): People in the control arm will receive a combination of vitamins and trace elements; people in the experimental arms will receive hydroxychloroquine, or favipiravir, or imatinib, or telmisartan. MAIN OUTCOME: The primary outcome is the proportion of participants with an incidence of hospitalisation and/or death between inclusion and day 14 in each arm. RANDOMISATION: Participants are randomized in a 1:1:1:1:1 ratio to each arm using a web-based randomisation tool. Participants not treated with an ARB or ACEI prior to enrolment are randomized to receive the comparator or one of the four experimental drugs. Participants already treated with an ARB or ACEI are randomized to receive the comparator or one of the experimental drugs except telmisartan (i.e.: hydroxychloroquine, imatinib, or favipiravir). Randomisation is stratified on ACEI or ARBs treatment at inclusion and on the type of residence (personal home vs. nursing home). BLINDING (MASKING): This is an open-label trial. Participants, caregivers, investigators and statisticians are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 1057 participants will be enrolled if all arms are maintained until the final analysis and no additional arm is added. Three successive futility interim analyses are planned, when the number of participants reaches 30, 60 and 102 in the control arm. Two efficacy analyses (interim n°3 and final) will be performed successively. TRIAL STATUS: This describes the Version 1.2 (April 8th, 2020) of the COVERAGE protocol that was approved by the French regulatory authority and ethics committee. The trial was opened for enrolment on April 15th, 2020 in the Nouvelle Aquitaine region (South-West France). Given the current decline of the COVID-19 pandemic in France and its unforeseeable dynamic in the coming months, new trial sites in 5 other French regions and in Luxembourg are currently being opened. A revised version of the protocol was submitted to the regulatory authority and ethics committee on June 15th, 2020. It contains the following amendments: (i) Inclusion criteria: age ≥65 replaced by age ≥60; time since first symptoms <3 days replaced by time since first symptoms <5 days; (ii) Withdrawal of the hydroxychloroquine arm (due to external data); (iii) increase in the number of trial sites. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 22nd, 2020 (Identifier: NCT04356495): and on EudraCT on April 10th, 2020 (Identifier: 2020-001435-27). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of 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).


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/tratamiento farmacológico , Pacientes Ambulatorios/estadística & datos numéricos , Neumonía Viral/tratamiento farmacológico , Terapias en Investigación/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Amidas/uso terapéutico , Antihipertensivos/uso terapéutico , Antimaláricos/uso terapéutico , Antivirales/uso terapéutico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Tolerancia a Medicamentos , Estudios de Factibilidad , Francia/epidemiología , Hospitalización/tendencias , Humanos , Hidroxicloroquina/uso terapéutico , Mesilato de Imatinib/uso terapéutico , Luxemburgo/epidemiología , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/virología , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazinas/uso terapéutico , Conducta de Reducción del Riesgo , Telmisartán/uso terapéutico , Resultado del Tratamiento
17.
Trials ; 21(1): 847, 2020 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-33050947

RESUMEN

OBJECTIVES: Primary objective: To determine the efficacy of a candidate antiviral on time to virological cure compared to standard of care within 14 days of randomisation Secondary objectives: • To determine the safety of the antiviral • To determine the clinical benefit of the antiviral over placebo according to the WHO 7-point ordinal scale • To determine the clinical benefit of the antiviral over placebo on time to resolution of clinical symptoms • To determine the effect of the antiviral over placebo on biomarkers of inflammation and immune activation TRIAL DESIGN: This is a multi-centre, triple-blind, randomised placebo controlled phase II, 2-arm trial with parallel-group design with allocation ratio 1:1. PARTICIPANTS: Inclusion Criteria: • Provision of informed consent by the participant • Age ≥18 years • Confirmed SARS-CoV-2 by nucleic acid testing in the past 5 days • COVID-19 related symptom initiation within 5 days • Female patients of childbearing potential must have a negative pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 1 week following the last dose of study treatment. EXCLUSION CRITERIA: • Known allergy to the study medication • Is on another clinical trial investigating an antiviral treatment for COVID-19 • Pregnancy • Patients with severe hepatic dysfunction equivalent to Grade C in the Child-Pugh classification • Patients with renal impairment requiring dialysis • Is deemed by the Investigator to be ineligible for any reason Participants will be recruited from, and the study visits will take place at Alfred Hospital, Monash Health, Austin Health in Victoria, Australia for hospitalised participants as well as recruitment in the community in participants homes for eligible people not requiring hospitalisation. INTERVENTION AND COMPARATOR: The first candidate antiviral is favipiravir Arm 1: Favipiravir 1800 mg favipiravir BD on Day 1 followed by 800 mg BD favipiravir for the next 13 days. Arm 2: Placebo MAIN OUTCOMES: Primary outcome: Time to virological cure as defined by 2 successive throat (or combined nose/throat) swabs negative for SARS-CoV-2 by nucleic acid testing during the 14 days after enrolment. RANDOMISATION: Randomisation performed at the Alfred Hospital Clinical Trials Pharmacy using computer generated block-randomisation lists with 6 participants per block. Within each block half of the participants will be randomised to the candidate antiviral and the other half to placebo. Randomisation is stratified by study site, with participants enrolled in the community considered as a study site. BLINDING (MASKING): Study participants, study investigators and the study statistician will be blinded to treatment allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The study aims to recruit 190 people (95/arm) with the first candidate antiviral favipiravir TRIAL STATUS: Protocol version 2.0 Dated 31-Jul-2020. Recruitment will take place between July 2020 and December 2020. TRIAL REGISTRATION: clinicaltrials.gov NCT04445467 First posted 24-Jun-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.


Asunto(s)
Amidas/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Pirazinas/uso terapéutico , Amidas/efectos adversos , Antivirales/efectos adversos , Australia/epidemiología , Betacoronavirus/genética , Biomarcadores/metabolismo , Protocolos Clínicos , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Pandemias , Placebos/administración & dosificación , Neumonía Viral/epidemiología , Neumonía Viral/virología , Pirazinas/efectos adversos , Seguridad , Resultado del Tratamiento
18.
Proc Natl Acad Sci U S A ; 117(43): 26955-26965, 2020 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-33037151

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus has infected millions of people of which more than half a million succumbed to the viral disease, COVID-19. The urgent need for an effective treatment together with a lack of small animal infection models has led to clinical trials using repurposed drugs without preclinical evidence of their in vivo efficacy. We established an infection model in Syrian hamsters to evaluate the efficacy of small molecules on both infection and transmission. Treatment of SARS-CoV-2-infected hamsters with a low dose of favipiravir or hydroxychloroquine with(out) azithromycin resulted in, respectively, a mild or no reduction in virus levels. However, high doses of favipiravir significantly reduced infectious virus titers in the lungs and markedly improved lung histopathology. Moreover, a high dose of favipiravir decreased virus transmission by direct contact, whereas hydroxychloroquine failed as prophylaxis. Pharmacokinetic modeling of hydroxychloroquine suggested that the total lung exposure to the drug did not cause the failure. Our data on hydroxychloroquine (together with previous reports in macaques and ferrets) thus provide no scientific basis for the use of this drug in COVID-19 patients. In contrast, the results with favipiravir demonstrate that an antiviral drug at nontoxic doses exhibits a marked protective effect against SARS-CoV-2 in a small animal model. Clinical studies are required to assess whether a similar antiviral effect is achievable in humans without toxic effects.


Asunto(s)
Amidas/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Hidroxicloroquina/uso terapéutico , Pirazinas/uso terapéutico , Amidas/farmacocinética , Animales , Chlorocebus aethiops , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/virología , Cricetinae , Modelos Animales de Enfermedad , Transmisión de Enfermedad Infecciosa/prevención & control , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Femenino , Hidroxicloroquina/farmacocinética , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/virología , Pirazinas/farmacocinética , Resultado del Tratamiento , Células Vero , Carga Viral/efectos de los fármacos
19.
Balkan Med J ; 37(6): 341-347, 2020 10 23.
Artículo en Inglés | MEDLINE | ID: mdl-32865382

RESUMEN

Aims: Limited data about disease management strategies are available for pediatric patients with coronavirus disease-2019, particularly in Turkey. This study aimed to share the data on patients aged under 18 years in our country to be beneficial for understanding the disease course in children. Methods: A retrospective review of the medical records of pediatric patients aged under 18 years who were confirmed as coronavirus disease-2019 between March 11, and June 23, 2020, and were admitted to our hospitals was conducted. Results: A total of 220 pediatric patients with coronavirus disease-2019 were evaluated, of which 48.2% were boys, with a median age of 10 years, and 9.5% had underlying diseases. Patients were classified according to severity, with the percentages of asymptomatic, mild, moderate, and critical/severe cases determined to be 25.5%, 45%, 26.8%, and 2.7%, respectively. Extracorporeal membrane oxygenation was required in two patients (0.9%) and mechanical ventilation in three (1.4%). Targeted therapies were used in six patients (2.7%), with hydroxychloroquine being the most commonly used agent either alone (one patient) or in combination with favipiravir (five patients). Two patients (0.9%) died, and nine (4.1%) were still hospitalized during the study period. Conclusion: Although the disease course of coronavirus disease-2019 seems to be mild in children, critical illness is significant, and the treatment strategy primarily should consist of supportive care according to our preliminary observations.


Asunto(s)
Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/terapia , Gravedad del Paciente , Neumonía Viral/complicaciones , Neumonía Viral/terapia , Adolescente , Amidas/uso terapéutico , Antimaláricos/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus , Niño , Preescolar , Infecciones por Coronavirus/diagnóstico , Oxigenación por Membrana Extracorpórea , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Pediátrico , Tiempo de Internación , Masculino , Pandemias , Neumonía Viral/diagnóstico , Pirazinas/uso terapéutico , Respiración Artificial , Estudios Retrospectivos , Resultado del Tratamiento , Turquia
20.
J Infect Chemother ; 26(12): 1324-1327, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32900659

RESUMEN

Most patients with coronavirus disease 2019 (COVID-19) have just only mild symptoms, but about 5% are very severe. Although extracorporeal membranous oxygenation (ECMO) is sometimes used in critically patients with COVID-19, ECMO is only an adjunct, not the main treatment. If the patient's condition deteriorates and it is determined to be irreversible, it is necessary to decide to stop ECMO. A 54-year-old man was admitted on day 6 of onset with a chief complaint of high fever and cough. Computed tomography (CT) showed a ground glass opacity in both lungs, and reverse transcription-polymerase chain reaction (RT-PCR) diagnosed COVID-19. He was admitted to the hospital and started to receive oxygen and favipiravir. After that, his respiratory condition deteriorated, and he was intubated and ventilated on day 9 of onset, and ECMO was introduced on day 12. Two days after the introduction of ECMO, C-reactive protein (CRP) increased, chest X-p showed no improvement in pneumonia, and PaO2/FiO2 decreased again. As D-dimer rose and found a blood clot in the ECMO circuit, we had to decide whether to replace the circuit and continue with ECMO or stop ECMO. At this time, the viral load by RT-PCR was drastically reduced to about 1/1750. We decided to continue ECMO therapy and replaced the circuit. The patient's respiratory status subsequently improved and ECMO was stopped on day 21 of onset. In conclusion, viral load measurement by RT-PCR may be one of the indicators for promoting the treatment of severe COVID-19 patients.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/virología , Oxigenación por Membrana Extracorpórea/métodos , Neumonía Viral/terapia , Neumonía Viral/virología , Carga Viral/métodos , Amidas/uso terapéutico , Antivirales/uso terapéutico , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Toma de Decisiones , Hospitalización , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico , Pirazinas/uso terapéutico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
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