Efficacy of Chloroquine or Hydroxychloroquine in Treating Pneumonia Caused by SARS-Cov-2 - COVID-19

Phase 3CompletedNCT04420247

Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva142 enrolled

Overview

Facing the challenge of finding an efficient treatment for COVID-19, the viral pneumonia caused by the Coronavirus SARS-Cov-2, this study intended to test if Chloroquine or Hydroxychloroquine, two drugs with strong in-vitro antiviral role proven by numerous studies and with a well defined safety profile established, for efficacy in treating COVID-19 and improving an ordinal primary outcome composed by a 9-levels scale, which was recomended by the World Health Organization.

This is a Phase 3, Pragmatic, Multicentric Randomized Controled Trial of efficacy to test the effect of either Chloroquine or Hydroxychloroquine for 5 days in the recomended dose standardized by brazilian Ministry of Health. Patients were randomized (1:1) using stratified randomization by hospital and severity at the moment of randomization (stipulated by use of mechanical ventilation or not) into two arms: Intervention and Control. Intervention group recieved a loading dose of 900mg of Chloroquine or 800mg of Hydroxycloroquine in the first day, followed by 450mg of chloroquine of 400mg of hydroxychloroquine. Primary and secondary outcomes were evaluated on the 5th, 7th, 10th, 14th, 28th day after randomization. Although the outcomes presented in the latest version were updated late on ClinicalTrials.org, on October 23, 2020, these outcomes were already present in the trial protocol approved by the Brazilian National Commission for Ethics in Research on April 8, 2020 (approval number: 3960331) and amending the protocol, approved by the same National Commission on May 25, 2020 (approval number: 4044848)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

142

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adult Males and non-pregnant females that accept and sign the informed consent. * Hospitalized with COVID-19 suspection that has collected the confirmatory test * To have at least one of thes symptoms: Fever, coughing, throat ache or runny nose. * To have at least one of these findings: radiological findings that indicates COVID-10 (bilatareal ground grass images); O2 saturation lower than 94% without supplementation and crackles in lung auscultation; Need of O2 supplementation; Need of Mechanical Ventilation. * Female patients must also agree to use efficient counterceptive methods during the evaluation period. Exclusion Criteria: * Patients with psoriasis or other exfoliative disease, porphyria, epilepsy, myasthenia gravis, advanced liver failure or glucose-6-phosphate dehydrogenase deficiency. * ALT / AST\> 5 times the upper limit of normal. * Severe chronic kidney disease in stage 4 or requiring dialysis (ie, eGFR \<30). * Pregnancy or breastfeeding. * Early transfer to another hospital that is not a study site within 72 hours. * Severe heart disease and / or a history of cardiac arrhythmia. * Allergy to Chloroquine and / or Hydroxychloroquine.

Outcomes

Primary Outcomes

World Health Organization (WHO) 9-levels ordinal scale (from 0-8)

Evaluation of the clinical status of patients on the 14th day after randomization defined by the 9-levels ordinal scale, with lower scores meaning better outcomes.

Time frame: 14 days after randomization

Secondary Outcomes

World Health Organization (WHO) 9-levels ordinal scale (from 0-8)

Evaluation of the clinical status of patients on the 5th, 7th, 10th and 28th day after randomization defined by the 9-levels ordinal scale, with lower scores meaning better outcomes.

Time frame: 5, 7, 10 and 28 days after randomization

Mortality

All-cause mortality at 28 days after randomization