Clinical trial NCT04420247: Efficacy of Chloroquine or Hydroxychloroquine in Treating Pneumonia Caused by SARS-Cov-2 - COVID-19
Official title: Multicentric Pragmatic Randomized Controled Trial to Evaluate the Efficacy Chloroquine or Hydroxychloroquine for Five Days in Treating Pneumonia Caused by SARS-Cov-2 - COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID
COVID-19
SARS-CoV 2
Coronavirus
Corona Virus Infection
Keywords: VIRAL PNEUMONIA
CORONAVIRUS
COVID-19
COVID
SARS-COV-2
Lead sponsor: Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva
Sponsor class: OTHER
First posted: 2020-06-09
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two arms - Intervention and Control Intervention received unblinded treatment with Chloroquine or Hyroxycloroquine for 5 days, as well as standard treatment available and recomended by the Brazilian Guidelines for COVID-19.

Control group received just the standard treatment available and recomended by the Brazilian Guidelines for COVID-19.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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)

Eligibility criteria: 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.

Primary outcomes:
measure: World Health Organization (WHO) 9-levels ordinal scale (from 0-8)
timeFrame: 14 days after randomization
Secondary outcomes:
measure: World Health Organization (WHO) 9-levels ordinal scale (from 0-8)
timeFrame: 5, 7, 10 and 28 days after randomization
measure: Mortality
timeFrame: 28 days after randomization
measure: Ventilation free days
timeFrame: 28 days after randomization
measure: ICU Lenght of Stay
timeFrame: 28 days after randomization
measure: Hospital Lenght of Stay
timeFrame: 28 days after randomization
measure: Acute Kidney Disease incidence
timeFrame: 28 days after randomization
measure: Percentage of patients needing dialysis
timeFrame: 28 days after randomization
measure: Coagulopathy incidence
timeFrame: 28 days after randomization
measure: Mean of C Reactive Protein Levels
timeFrame: 5, 7, 10, 14 and 28 days after randomization
measure: Sequential Organ Failure Assessment (SOFA) scores
timeFrame: 5, 7, 10, 14 and 28 days after randomization
measure: Neutrophils/lymphocytes ratio
timeFrame: 5, 7, 10, 14 and 28 days after randomization
Other outcomes:
measure: Arrhythmia
timeFrame: 28 days after randomization
Locations:
city: Curitiba
country: Brazil
facility: Centro de Estudos e Pesquisa em Emergencias Clinicas e Terapia Intensiva
state: Parana
Study officials:
References:
citation: Rea-Neto A, Bernardelli RS, Camara BMD, Reese FB, Queiroga MVO, Oliveira MC. An open-label randomized controlled trial evaluating the efficacy of chloroquine/hydroxychloroquine in severe COVID-19 patients. Sci Rep. 2021 Apr 27;11(1):9023. doi: 10.1038/s41598-021-88509-9.