Efficacy and safety of chloroquine plus primaquine for the treatment of Plasmodium vivax malaria in Hamusit site, Northwestern Ethiopia.

BACKGROUND: Plasmodium vivax malaria is still an important public health problem in Ethiopia. Unlike Plasmodium falciparum, P. vivax has a dormant liver stage (hypnozoite) that can be a risk of recurrent vivax malaria unless treated by radical cure with primaquine. Drug resistance to chloroquine is threatening malaria control and elimination efforts. This study assessed the therapeutic efficacy and safety of chloroquine plus 14 days of primaquine on P. vivax infection based on parasitological, clinical, and haematological parameters. METHODS: A single-arm in vivo prospective therapeutic efficacy study was conducted to assess the clinical and parasitological response to the first-line treatment of P. vivax in Ethiopia, chloroquine plus 14 days low dose of (0.25 mg/kg/day) primaquine between December 2022 and March 2023 at Hamusit Health Centre using the standard World Health Organization (WHO) protocol. A total of 100 study participants with P. vivax mono-infection who were over 6 months old were enrolled and monitored for adequate clinical and parasitological responses for 42 days. The WHO double-entry Excel sheet and SPSS v.25 software were used for Kaplan-Meier survival analysis, and a paired t-test was used for analysis of haemoglobin improvements between follow up days. RESULTS: A total of 100 patients were enrolled among those, 96% cases were rural residents, 93% had previous malaria exposure, and predominant age group was 5-15 years (61%). 92.6% (95% CI 85.1-96.4%) of enrolled patients were adequate clinical and parasitological response, and 7.4% (95% CI 3.6-14.9%) recurrences were observed among treated patients. The fever and parasite clearance rate on day 3 were 98% and 94%, respectively. The baseline haemoglobin levels improved significantly compared to those days 14 and 42 (p < 0.001). No serious adverse event was observed during the study period. CONCLUSIONS: In this study, co-administration of chloroquine with primaquine was efficacious and well-tolerated with fast resolution of fever and high parasites clearance rate. However, the 7.4% failure is reported is alarming that warrant further monitoring of the therapeutic efficacy study of P. vivax.

Optimal balance of benefit versus risk for tafenoquine in the treatment of Plasmodium vivax malaria.

A single 300 mg dose of tafenoquine (an 8-aminoquinoline), in combination with a standard 3-day course of chloroquine, is approved in several countries for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients aged ≥ 16 years. Despite this, questions have arisen on the optimal dose of tafenoquine. Before the availability of tafenoquine, a 3-day course of chloroquine in combination with the 8-aminoquinoline primaquine was the only effective radical cure for vivax malaria. The World Health Organization (WHO)-recommended standard regimen is 14 days of primaquine 0.25 mg/kg/day or 7 days of primaquine 0.5 mg/kg/day in most regions, or 14 days of primaquine 0.5 mg/kg/day in East Asia and Oceania, however the long treatment courses of 7 or 14 days may result in poor adherence and, therefore, low treatment efficacy. A single dose of tafenoquine 300 mg in combination with a 3-day course of chloroquine is an important advancement for the radical cure of vivax malaria in patients without glucose-6-phosphate dehydrogenase (G6PD) deficiency, as the use of a single-dose treatment will improve adherence. Selection of a single 300 mg dose of tafenoquine for the radical cure of P. vivax malaria was based on collective efficacy and safety data from 33 studies involving more than 4000 trial participants who received tafenoquine, including over 800 subjects who received the 300 mg single dose. The safety profile of single-dose tafenoquine 300 mg is similar to that of standard-dosage primaquine 0.25 mg/kg/day for 14 days. Both primaquine and tafenoquine can cause acute haemolytic anaemia in individuals with G6PD deficiency; severe haemolysis can lead to anaemia, kidney damage, and, in some cases, death. Therefore, relapse prevention using an 8-aminoquinoline must be balanced with the need to avoid clinical haemolysis associated with G6PD deficiency. To minimize this risk, the WHO recommends G6PD testing for all individuals before the administration of curative doses of 8-aminoquinolines. In this article, the authors review key efficacy and safety data from the pivotal trials of tafenoquine and argue that the currently approved dose represents a favourable benefit-risk profile.

Recent findings about antimalarials in cutaneous lupus erythematosus: What dermatologists should know.

Antimalarials (AMs), particularly hydroxychloroquine (HCQ) and chloroquine (CQ), are the cornerstone of the treatment for both systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). HCQ and CQ are recommended as first-line oral agents in all CLE guidelines. Initially thought to have potential therapeutic effects against COVID-19, HCQ has drawn significant attention in recent years, highlighting concerns over its potential toxicity among patients and physicians. This review aims to consolidate current evidence on the efficacy of AMs in CLE. Our focus will be on optimizing therapeutic strategies, such as switching from HCQ to CQ, adding quinacrine to either HCQ or CQ, or adjusting HCQ dose based on blood concentration. Additionally, we will explore the potential for HCQ dose reduction or discontinuation in cases of CLE or SLE remission. Our review will focus on the existing evidence regarding adverse events linked to AM usage, with a specific emphasis on severe events and those of particular interest to dermatologists. Last, we will discuss the optimal HCQ dose and the balance between preventing CLE or SLE flares and minimizing toxicity.

Operational effectiveness of tafenoquine and primaquine for the prevention of Plasmodium vivax recurrence in Brazil: a retrospective observational study.

BACKGROUND: Prevention of Plasmodium vivax malaria recurrence is essential for malaria elimination in Brazil. We evaluated the real-world effectiveness of an updated treatment algorithm for P vivax radical cure in the Brazilian Amazon. METHODS: In this non-interventional observational study, we used retrospective data from the implementation of a P vivax treatment algorithm at 43 health facilities in Manaus and Porto Velho, Brazil. The treatment algorithm consisted of chloroquine (25 mg/kg over 3 days) and point-of-care quantitative glucose-6-phosphate dehydrogenase (G6PD) testing followed by single-dose tafenoquine 300 mg (G6PD normal, aged ≥16 years, not pregnant and not breastfeeding), 7-day primaquine 0·5 mg/kg per day (G6PD intermediate or normal, aged ≥6 months, not pregnant, and not breastfeeding or breastfeeding for >1 month), or primaquine 0·75 mg/kg per week for 8 weeks (G6PD deficient, aged ≥6 months, not pregnant, and not breastfeeding or breastfeeding for >1 month). P vivax recurrences were identified from probabilistic linkage of routine patient records from the Brazilian malaria epidemiological surveillance system. Recurrence-free effectiveness at day 90 and day 180 was estimated using Kaplan-Meier analysis and hazard ratios (HRs) by multivariate analysis. This clinical trial is registered with ClinicalTrials.gov, NCT05096702, and is completed. FINDINGS: Records from Sept 9, 2021, to Aug 31, 2022, included 5554 patients with P vivax malaria. In all treated patients of any age and any G6PD status, recurrence-free effectiveness at day 180 was 75·8% (95% CI 74·0-77·6) with tafenoquine, 73·4% (71·9-75·0) with 7-day primaquine, and 82·1% (77·7-86·8) with weekly primaquine. In patients aged at least 16 years who were G6PD normal, recurrence-free effectiveness until day 90 was 88·6% (95% CI 87·2-89·9) in those who were treated with tafenoquine (n=2134) and 83·5% (79·8-87·4) in those treated with 7-day primaquine (n=370); after adjustment for confounding factors, the HR for recurrence following tafenoquine versus 7-day primaquine was 0·65 (95% CI 0·49-0·86; p=0·0031), with similar outcomes between the two treatments at day 180 (log-rank p=0·82). Over 180 days, median time to recurrence in patients aged at least 16 years who were G6PD normal was 92 days (IQR 76-120) in those treated with tafenoquine and 68 days (52-94) in those treated with 7-day primaquine. INTERPRETATION: In this real-world setting, single-dose tafenoquine was more effective at preventing P vivax recurrence in patients aged at least 16 years who were G6PD normal compared with 7-day primaquine at day 90, while overall efficacy at 180 days was similar. The public health benefits of the P vivax radical cure treatment algorithm incorporating G6PD quantitative testing and tafenoquine support its implementation in Brazil and potentially across South America. FUNDING: Brazilian Ministry of Health, Municipal and State Health Secretariats; Fiocruz; Medicines for Malaria Venture; Bill & Melinda Gates Foundation; Newcrest Mining; and the UK Government. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Effect of quercetin and role of nitric oxide pathway in chloroquine-induced scratching

Abstract Nitric oxide (NO) is an abundant mediator which is demonstrated to be involved in pruritus. Assuming that the increased NO also mediates chloroquine-induced pruritus, which is a frequent complication seen in the chronic chloroquine treatment, the current study aimed to investigate the effect of quercetin and the role of NO in chloroquine-induced pruritus in C57BL/6 mice. Model was created with subcutaneous chloroquine (400µg/site) injection to the nape of the mice. Effect of quercetin and role of NO were investigated with administration of quercetin, and co-administration with L-NAME, 7-NI and L-arginine before chloroquine injection. Locomotor activity was assessed by activity cage and number of the scratching bouts after chloroquine injection was recorded for 30 minutes. Our results show that quercetin significantly reduced scratching bouts at the doses of 10, 20, 40 and 80 mg/kg. Locomotor activity was decreased at the 40 and 80 mg/kg doses of quercetin. Additionally, decrease of the number of scratching bouts by quercetin prevented by L-arginine treatment, while L-NAME and 7-NI enhanced the anti-pruritic effect of sub-effective doses of quercetin. Therefore, our study demonstrated that acute injection of quercetin significantly diminished chloroquine-induced scratching behavior, and this effect is partly mediated by inhibition of neuronal nitric oxide synthase enzyme.

Chloroquine ameliorates adriamycin-induced testicular damage by suppressing the inflammation and apoptosis in rats: a histological, immunohistochemical and biochemical study / La cloroquina mejora el daño testicular inducido por la adriamicina al suprimir la inflamación y la apoptosis en ratas: un estudio histológico, inmunohistoquímico y bioquímico

SUMMARY: Adriamycin (ADR) is an anthracycline antibiotic used for treatment of many types of cancer. However, its applications may damage to healthy tissues. Chloroquine (CLQ) is an anti-inflammatory agent used in treatment of many inflammation associated diseases such as malaria and rheumatoid arthritis. Moreover, it is used in the treatment of pneumonia caused by COVID-19. The aim of this study is to determine possible therapeutic effects of Chloroquine on Adriamycin-induced testicular toxicity in rats. We investigated the effect of CLQ on testicular injury caused by ADR. Rats were divided into four groups: Control, ADR, CLQ, ADR+CLQ. After administrations, animals were sacrificed, and testis tissues were extracted from the animals for the further examinations. Histopathological changes in testis tissues were evaluated and TNF-α and IL-6 immunostaining were performed to determine the expression levels of these cytokines. TUNEL method were used for evaluation of apoptotic index. Moreover, serum testosterone levels were measured by ELISA assay. We observed that ADR group showed histopathological deterioration when compared to the Control group and CLQ treatment ameliorated this damage induced by Adriamycin.An increase in TNF-α and IL-6 immunoreactivities and in the number of apoptotic cells and a decrease in serum testosterone levels were determined in the ADR group compared to the Control and CLQ group. Furthermore, our examinations showed an improvement in testicular tissue in ADR+CLQ group in terms of these parameters when compared to the ADR group. We suggest that CLQ can be used as a protective agent to reduce the toxic effects of Adriamycin as a result of its anti-inflammatory and anti-apoptotic properties.

RESUMEN: La adriamicina (ADR) es un antibiótico de antraciclina que se usa para el tratamiento de muchos tipos de cáncer. Sin embargo, sus aplicaciones pueden dañar los tejidos sanos. La cloroquina (CLQ) es un agente antiinflamatorio que se utiliza en el tratamiento de enfermedades asociadas a la inflamación, tal como la malaria y la artritis reumatoide. También se utiliza en el tratamiento de la neumonía causada por COVID-19. El objetivo de este estudio fue determinar los posibles efectos terapéuticos de la cloroquina sobre la toxicidad testicular inducida por adriamicina en ratas. Investigamos el efecto de CLQ sobre la lesión testicular causada por ADR. Las ratas se dividieron en cuatro grupos: Control, ADR, CLQ, ADR + CLQ. Después de las administraciones, se sacrificaron los animales y se extrajeron los testículos de los animales para los exámenes adicionales. Se evaluaron los cambios histopatológicos en los tejidos testiculares y se realizó la inmunotinción de TNF-α e IL-6 para determinar los niveles de expresión de estas citocinas. Se utilizó el método TUNEL para la evaluación del índice apoptótico. Además, los niveles de testosterona en suero se midieron mediante un ensayo ELISA. El grupo ADR mostró un deterioro histopatológico en comparación con el grupo Control y observamos que el tratamiento con CLQ mejoró el daño inducido por Adriamicina. Un aumento en las inmunorreactividades de TNF-α e IL-6 y en el número de células apoptóticas además de una disminución en los niveles séricos de testosterona se determinaron en el grupo de ADR en comparación con el grupo de control y CLQ. Además, nuestros exámenes mostraron una mejora en el tejido testicular en el grupo ADR + CLQ en términos de estos parámetros en comparación con el grupo ADR. Sugerimos que CLQ se puede utilizar como agente protector para reducir los efectos tóxicos de la Adriamicina, gracias a sus propiedades antiinflamatorias y antiapoptóticas.

Mecanismos de acción de agentes propuestos para el tratamiento farmacológico específico de la infección por SARS-CoV-2 / Mechanisms of action of proposed agents for the specific pharmacological treatment of SARS-CoV-2 infection

Resumen Desde la notificación de la pandemia por SARS-CoV-2, agente patógeno responsable del COVID-19, muchos de los tratamientos dirigidos a su manejo han estado sometidos a estudios de manera constante, con el fin de comprobar su eficacia y seguridad. El conocimiento de su virología y etiopatogenia posibilitaría objetivar los pasos moleculares específicos que puedan ser blancos terapéuticos de variados fármacos actualmente disponibles. Esta experiencia proviene principalmente de las infecciones por SARS-CoV y MERS-CoV, con resultados variados 'in vitro' en el SARS-CoV-2, sin evidencia clínica que demuestre efectividad y seguridad de dichos tratamientos. A la fecha, no se ha podido concretar con claridad un esquema de tratamiento específico, debido a que la evidencia surgida ha puesto en jaque cada uno de los fármacos propuestos. Esto ha motivado a continuar en la búsqueda de una estrategia efectiva que permita manejar esta pandemia con la seguridad y eficacia necesaria para que el beneficio terapéutico esté por sobre los posibles efectos adversos que estos esquemas farmacológicos pudiesen presentar. La siguiente revisión pretende mostrar la evidencia disponible a la fecha, definiendo la actividad de cada fármaco en función de su mecanismo de acción.

Since the beginning of the pandemic by SARS-CoV-2, the pathogen responsible for COVID-19, many of the therapeutic options for its management have been under constant revision, in order to verify their safety and efficiency. Knowledge of the viral structure and pathogenesis make it possible to determine the molecular pathways that may be targeted with current available drugs. The experience with these drugs comes mainly from infections caused by SARS-CoV and MERS-CoV, in vitro studies with SARS-CoV-2 that yield variable results, and clinical experience that does not ensure effectiveness and safety of such drugs. To date, it has not been possible to elucidate a specific treatment scheme, because of the constant release of evidence that challenges the usefulness of the proposed drugs. This has motived us to continue seeking for an effective strategy that allows to manage this pandemic in a safe and efficient manner, so that therapeutic benefit surpasses the related adverse drug reactions that can occur. The following review aims to showcase the evidence available to date by defining the activity of each drug based on its mechanism of action.

Quinolinotriazole antiplasmodials via click chemistry: synthesis and in vitro studies of 7-Chloroquinoline-based compounds

Malaria is nowadays one of the most serious health concerns in a global scale and, although there is an evident increase in research studies in this area, pointed by the vast number of hits and leads, it still appears as a recurrent topic every year due to the drug resistance shown by the parasite exposing the urgent need to develop new antimalarial medications. In this work, 38 molecules were synthesized via copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) or "click" chemistry, following different routes to produce 2 different organic azides, obtained from a 4,7 dicholoquinoline, reacted with 19 different commercially available terminal alkynes. All those new compounds were evaluated for their in vitro activity against the chloroquine resistant malaria parasite Plasmodium falciparum (W2). The cytotoxicity evaluation was accomplished using Hep G2 cells and SI index was calculated for every molecule. Some of the quinoline derivatives have shown high antimalarial activity, with IC50 values in the range of 1.72-8.66 µM, low cytotoxicity, with CC50>1000 µM and selectivity index (SI) in the range of 20-100, with some compounds showing SI>800. Therefore, the quinolinotriazole hybrids could be considered a very important step on the development of new antimalarial drugs

Tratamiento farmacológico en tiempos de incertidumbre: uso de la hidroxicloroquina/cloroquina en el tratamiento de COVID-19 / Pharmacological treatment in uncertainty times: hydroxychloroquine/chloroquine use in the COVID-19 treatment

ANTECEDENTES Y OBJETIVOS: En los momentos de extrema gravedad en los que nos encontramos, y ante la incertidumbre acerca de los tratamientos más eficaces en la lucha contra la enfermedad COVID-19 y con el objetivo de conocer las evidencias que pueden sostener la recomendación de utilización de cloroquina/hidroxicloroquina en el COVID 19, se realizó una revisión sistemática de estudios publicados y EC puestos en marcha con fecha hasta 28 de abril 2020. MATERIAL Y MÉTODOS: Se realizó una búsqueda sistemática en PubMed con las palabras clave COVID-19 y sus sinónimos y cloroquina/hidroxicloroquina. La selección y extracción de los datos aparecidos en dicha búsqueda fue realizada por dos investigadores de forma independiente. Los resultados se discutieron con un grupo clínico de médicos de Atención Primaria y se sintetizaron los resultados mediante tablas de GRADE. RESULTADOS: Se encontró una revisión sistemática de buena calidad que incluye artículos con elevado riesgo de sesgos. Y 8 EC puestos en marcha que arrojarán resultados más allá de mayo de 2020. CONCLUSIONES: Aunque las conclusiones de la revisión sistemática generan una baja confianza en los resultados, y las variables clínicas que muestran beneficio son variables intermedias, los efectos secundarios son asumibles y podrían ser minimizados con el uso de herramientas de riesgo de alargamiento del QT, por lo que se podría hacer una recomendación débil a favor del uso de cloroquina/hidroxicloroquina en pacientes con COVID-19 en estadio leve-moderado

BACKGROUND AND OBJECTIVES: In this moments, of extreme gravity in which we find ourselves, and in the uncertainty face about the most effective treatment against COVID-19 disease and with the aim of find the evidence that support the chloroquine/hydroxychloroquine use recommendation to treat COVID-19 disease, a systematic review of published studies and RCT studies publishes until April 28, 2020 was carried out. MATERIAL AND METHODS: A systematic search was carried out in PubMed with the keywords COVID-19 and their synonyms and hydroxychloroquine/chloroquine. The data selection and extraction was elaborated by two researchers, independently. The results were discussed with a Primary Care physicians clinical group and the results were synthesized using GRADE methodology. RESULTS: A good quality systematic review was found that includes articles with a high risk of bias. And 8 EC launched that will produce results beyond May 2020. CONCLUSIONS: Although the conclusions of the systematic review generate a low confidence in the results, and the clinical variables that show benefit are intermediate variables, the side effects are acceptable and could be minimized with the use of QT lengthening risk tools, so it is could make a weak recommendation in favor of the use of chloroquine/hydroxychloroquine in patients with mild-moderate stage COVID-19

COVID-19: la pandemia por el nuevo virus SARS-CoV-2

RESUMEN Durante las primeras semanas de 2020 se comenzaron a informar casos de personas con SARS-CoV-2 fuera de China, con un rápido aumento de casos y muertes en todo el mundo. El SARS-CoV-2 es un virus ARN monocatenario positivo, envuelto en una bicapa lipídica derivada de la membrana celular del huésped y constituido por cuatro proteínas estructurales (S, M, E y N), además de una hemaglutinina-esterasa. La unión de la proteína S con el receptor de enzima convertidora de angiotensina 2 (ECA2) permite la entrada del virus a la célula huésped y es una potencial diana terapéutica. El 81% de los enfermos hace cuadro leve; el 14%, grave; y el 5% requiere cuidados intensivos. La fiebre es el síntoma más frecuente, seguido de tos y disnea. La mayoría de los pacientes no presentan leucocitosis pero sí linfopenia, con cultivos de esputo que no muestran otros patógenos. En las biopsias de pulmón de pacientes graves el hallazgo más llamativo es el daño alveolar difuso. Radiológicamente se aprecian patrones de vidrio esmerilado y alveolar, siendo las lesiones de predominio basal, subpleural y posterior, con una distribución periférica multifocal, afectando más el lóbulo inferior derecho. Hay una marcada respuesta inflamatoria, que llega hasta la tormenta de citoquinas, en la que el tratamiento antiinflamatorio con terapia de pulso con metilprednisolona estaría indicado. Aunque no existan estudios en gran escala respecto al uso de cloroquina/hidroxicloroquina, debido a la situación mundial se ha autorizado su uso por su efecto anti SARS-CoV-2 y anti-inflamatorio, el cual puede ser potenciado con el uso de azitromicina.

ABSTRACT During the first weeks of 2020, cases of SARS-CoV-2 began to be reported outside of China, with a rapid increase in cases and deaths worldwide. SARS-CoV-2 is a positive single-stranded RNA virus, encased in a lipid bilayer derived from the host cell membrane and consists of four structural proteins (S, M, E and N), plus a haemagglutinin-sterase. The binding of the S protein to the ECA2 receptor allows the entry of the virus into the host cell and is a potential therapeutic target. 81% of patients develop mild symptoms, 14% have severe symptoms and 5% require intensive care management. Fever is the most frequent symptom, followed by cough and dyspnea. Most patients do not present leukocytosis, but they do present lymphopenia with sputum cultures that do not show other pathogens. In lung biopsies of severe patients, the most noticeable finding is diffuse alveolar damage. Radiologically, ground glass and alveolar patterns are observed; the lesions being predominantly basal, subpleural, and posterior, with a multifocal peripheral distribution, more affecting the right lower lobe. There is a marked inflammatory response, up to the cytokine storm, in which anti-inflammatory treatment with pulse therapy with methylprednisolone would be indicated. Although there are no large-scale studies regarding the use of chloroquine / hydroxychloroquine, due to the global situation, its use has been authorized for its anti-SARS-CoV-2 and anti-inflammatory effect, which can be potentiated with the use of azithromycin.

Informe diário de evidências: COVID-19 busca realizada entre 17 e 19 de abril de 2020 / Daily evidence report: COVID-19 search conducted between April 17 and 19, 2020

Na comparação 1: hidroxicloroquina (HCQ) versus grupo controle/terapia padrão: quanto a cura clínica, normalização da temperatura corporal e número de dias de tosse, o grupo da HCQ sugere benefício quando comparado ao grupo controle. Em termos de cura virológica e morte/progressão da doença após o início do tratamento com HCQ, não houve diferença significativa em relação ao grupo controle. Ainda nessa mesma comparação entre os grupos, quando realizado tratamento com HCQ, observou-se menos casos com progressão radiológica quando comparado ao grupo controle. Quando se avaliou a segurança, não houve diferença significativa entre os grupos. Na metanálise, foi verificado um benefício no grupo controle/tratamento padrão quanto à progressão radiológica. Na comparação 2: HCQ associado à azitromicina (AZT) ou outras drogas versus controle/terapia padrão: em um dos estudos, 100% dos pacientes estava com cura virológica ao usar HCQ/AZT no dia 6, comparado a 57,1% em monoterapia com HCQ. Em um dos estudos, o teste de PCR positivou novamente em um paciente que ficou negativo para a PCR por tratamento com HCQ + Azitromicina. Em um dos estudos, 11% da população em terapia combinada teve prolongamento significativo do QTc (> 500 ms) e o desenvolvimento de insuficiência renal aguda foi um importante preditor de prolongamento extremo do QTc. Ainda não se pode admitir o benefício da associação do tratamento da HCQ com a AZT, pois são necessários mais estudos clínicos para uma conclusão definitiva sobre essa associação.1

Informe diário de evidências: COVID-19 busca realizada em 21 de abril de 2020 / Daily evidence report: COVID-19 search conducted on April 21, 2020

Três coortes foram avaliadas: pacientes que receberam hidroxicloroquina (HC) (n = 97), pacientes que receberam hidroxicloroquina e azitromicina (HC+AZ) (n = 113) e pacientes não expostos a hidroxicloroquina (sem HC) (n = 158). Nos três grupos, houveram mortes de pacientes: HC ­ 27 mortes (27,8 %), HC+AZ ­ 25 mortes (22,1 %) e sem HC ­ 18 mortes (11,4 %). A análise da associação das terapias (HC+AZ) com o risco de morte geral demonstrou que o grupo HC teria maior risco de morte por qualquer causa quando comparado ao grupo sem HC (p = 0,03). Não houve diferença em mortalidade na comparação do grupo HC+AZ com o grupo sem HC (p = 0,72). O uso de HC com ou sem a AZ não reduziu a mortalidade dos pacientes. Pelo contrário, o uso de apenas HC foi associado a um risco maior de morte quando comparado ao atendimento padrão, ou seja, sem HC. A necessidade da ventilação mecânica nos três grupos também foi estimada, mas não apresentou diferença significativa (p = 0,547).1

Informe diário de evidências: COVID-19 busca realizada em 20 de abril de 2020 / Daily evidence report: COVID-19 search conducted on April 20, 2020

Os autores destacam que o grande número de estudos realizados com a cloroquina (CQ) reflete o esforço que a comunidade científica está fazendo para esclarecer o papel desse fármaco na redução da mortalidade associada ao COVID-19. Contudo, segundo os autores, esse esforço provavelmente não está sendo suficientemente bem coordenado. Sugerem que ensaios clínicos adaptativos sejam conduzidos, a fim de responder adequadamente - e rapidamente - a diferentes questões observadas durante essa pandemia. Ressaltam que problemas em ensaios clínicos, como grande número amostral e duração prolongada dos estudos, falta de poder para avaliar a eficácia global ou em subgrupos importantes, e custo elevado dos ensaios, acabam limitando a inovação médica, especialmente nesse cenário de emergência. Por fim, sugerem que pontos importantes ainda precisam ser abordados, a fim de encontrar prontamente as respostas, enquanto a pandemia está em andamento. Tais pontos envolvem o uso de um grupo placebo para mostrar efetivamente a eficácia do tratamento; a falta de um rápido financiamento; a necessidade de aprovação oportuna do protocolo por conselhos éticos em todo o mundo; o uso de estudos multicêntricos em vez de estudos unicêntricos, e a conformidade dos protocolos com as boas práticas clínicas

Informe diário de evidências: COVID-19 busca realizada em 14 de abril de 2020 / Daily evidence report: COVID-19 search conducted on April 14, 2020

Este estudo incluiu dados coletados em tempo real de 181 pacientes internados com pneumonia por COVID-19; 84 receberam HCQ dentro de 48 horas de admissão (grupo HCQ) e 97 não receberam (grupo não HCQ). A gravidade inicial foi equilibrada entre os grupos, o que significa que esse fator de confusão foi endereçado. Na análise ponderada, 20,2% dos pacientes do grupo HCQ foram transferidos para a UTI ou morreram dentro de 7 dias versus 22,1% no grupo sem HCQ (16 vs. 21 eventos, RR 0,91, IC 95% 0,47-1,80). No grupo HCQ, 2,8% dos pacientes morreram em 7 dias versus 4,6% no grupo não HCQ (3 vs. 4 eventos, RR 0,61, IC 95% 0,13-2,89), e 27,4% e 24,1%, respectivamente, desenvolveram síndrome do desconforto respiratório agudo em 7 dias (24 vs. 23 eventos, RR 1,14, IC 95% 0,65-2,00). Oito pacientes que receberam HCQ (9,5%) tiveram modificações no eletrocardiograma que exigiram a descontinuação da HCQ. O tratamento com HCQ + tratamento padrão, não foi associado à redução de internações em UTIs ou óbito em 7 dias após a internação, em comparação com o tratamento padrão. Esses resultados não apoiam o uso de HCQ em pacientes hospitalizados com pneumonia por COVID-19.