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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04420247
• Other study ID #: CLOROTRIAL
• Status: Completed
• Phase: Phase 3
• Start date: April 16, 2020
• Est. completion date: September 3, 2020

Study information

• Verified date: May 2021
• Source: Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 142
• Est. completion date: September 3, 2020
• Est. primary completion date: August 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Corona Virus Infection
• Coronavirus
• Coronavirus Infections
• COVID
• COVID-19
• Pneumonia
• SARS-CoV 2

Intervention

Drug:
• Chloroquine
5 days of treatment with Chloroquine + Standard Care
• Hydroxychloroquine
5 days of treatment with Hydroxychloroquine + Standard Care

Other:
• standard care
Standard Care according to Brazilian Guidelines for treating COVID-19

Locations

Country	Name	City	State
Brazil	Centro de Estudos e Pesquisa em Emergencias Clinicas e Terapia Intensiva	Curitiba	Parana

Sponsors (1)

Lead Sponsor	Collaborator
Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Arrhythmia	Safety outcome: Any kind of arrhythmia identified by the attending physician at the time of the intercurrence, confirmed by an electrocardiogram (ECG), sometime until the 28th day	28 days after randomization
Primary	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.	14 days after randomization
Secondary	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.	5, 7, 10 and 28 days after randomization
Secondary	Mortality	All-cause mortality at 28 days after randomization	28 days after randomization
Secondary	Ventilation free days	Number of days without need of Mechanical Ventilation at 28 days after randomization	28 days after randomization
Secondary	ICU Lenght of Stay	ICU Lenght of Stay on survivors at 28 days after randomization	28 days after randomization
Secondary	Hospital Lenght of Stay	Hospital Lenght of Stay on survivors at 28 days after randomization	28 days after randomization
Secondary	Acute Kidney Disease incidence	Acute Kidney Disease incidence measured by Kidney Disease Improving Global Outcomes (KDIGO) stage 3 sometime until the 28th day after randomization.	28 days after randomization
Secondary	Percentage of patients needing dialysis	Percentage of patients needing dialysis sometime until the 28th day.	28 days after randomization
Secondary	Coagulopathy incidence	Presence of coagulopathy sometime until the 28th day (platelets < 150000 and/or INR >1.5 and/or KPTT > 35 seconds).	28 days after randomization
Secondary	Mean of C Reactive Protein Levels	Mean of C Reactive Protein Levels on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization	5, 7, 10, 14 and 28 days after randomization
Secondary	Sequential Organ Failure Assessment (SOFA) scores	Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization.	5, 7, 10, 14 and 28 days after randomization
Secondary	Neutrophils/lymphocytes ratio	Neutrophils/lymphocytes ratio on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization.	5, 7, 10, 14 and 28 days after randomization