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

Primary Purpose

COVID, COVID-19, SARS-CoV 2

Status
Completed
Phase
Phase 3
Locations
Brazil
Study Type
Interventional
Intervention
Chloroquine
Hydroxychloroquine
standard care
Sponsored by
Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID focused on measuring VIRAL PNEUMONIA, CORONAVIRUS, COVID-19, COVID, SARS-COV-2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Centro de Estudos e Pesquisa em Emergencias Clinicas e Terapia Intensiva

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intervention

Control

Arm Description

Treatment with either Chloroquine or Hydroxychloroquine according to what was available in the hospital: Chloroquine - 900mg on the first day, followed by 450mg in the next 4 days. Hydroxychloroquine - 800mg on the first day, followed by 450mg in the next 4 days. + Standard treatment available and recomended by the Brazilian Guidelines for COVID-19.

Standard treatment available and recomended by the Brazilian Guidelines for COVID-19.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Mortality
All-cause mortality at 28 days after randomization
Ventilation free days
Number of days without need of Mechanical Ventilation at 28 days after randomization
ICU Lenght of Stay
ICU Lenght of Stay on survivors at 28 days after randomization
Hospital Lenght of Stay
Hospital Lenght of Stay on survivors at 28 days after randomization
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.
Percentage of patients needing dialysis
Percentage of patients needing dialysis sometime until the 28th day.
Coagulopathy incidence
Presence of coagulopathy sometime until the 28th day (platelets < 150000 and/or INR >1.5 and/or KPTT > 35 seconds).
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
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.
Neutrophils/lymphocytes ratio
Neutrophils/lymphocytes ratio on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization.

Full Information

First Posted
June 2, 2020
Last Updated
May 10, 2021
Sponsor
Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva
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1. Study Identification

Unique Protocol Identification Number
NCT04420247
Brief Title
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

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
April 16, 2020 (Actual)
Primary Completion Date
August 20, 2020 (Actual)
Study Completion Date
September 3, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID, COVID-19, SARS-CoV 2, Coronavirus, Corona Virus Infection
Keywords
VIRAL PNEUMONIA, CORONAVIRUS, COVID-19, COVID, SARS-COV-2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
142 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intervention
Arm Type
Experimental
Arm Description
Treatment with either Chloroquine or Hydroxychloroquine according to what was available in the hospital: Chloroquine - 900mg on the first day, followed by 450mg in the next 4 days. Hydroxychloroquine - 800mg on the first day, followed by 450mg in the next 4 days. + Standard treatment available and recomended by the Brazilian Guidelines for COVID-19.
Arm Title
Control
Arm Type
Active Comparator
Arm Description
Standard treatment available and recomended by the Brazilian Guidelines for COVID-19.
Intervention Type
Drug
Intervention Name(s)
Chloroquine
Intervention Description
5 days of treatment with Chloroquine + Standard Care
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Intervention Description
5 days of treatment with Hydroxychloroquine + Standard Care
Intervention Type
Other
Intervention Name(s)
standard care
Intervention Description
Standard Care according to Brazilian Guidelines for treating COVID-19
Primary Outcome Measure Information:
Title
World Health Organization (WHO) 9-levels ordinal scale (from 0-8)
Description
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 Outcome Measure Information:
Title
World Health Organization (WHO) 9-levels ordinal scale (from 0-8)
Description
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
Title
Mortality
Description
All-cause mortality at 28 days after randomization
Time Frame
28 days after randomization
Title
Ventilation free days
Description
Number of days without need of Mechanical Ventilation at 28 days after randomization
Time Frame
28 days after randomization
Title
ICU Lenght of Stay
Description
ICU Lenght of Stay on survivors at 28 days after randomization
Time Frame
28 days after randomization
Title
Hospital Lenght of Stay
Description
Hospital Lenght of Stay on survivors at 28 days after randomization
Time Frame
28 days after randomization
Title
Acute Kidney Disease incidence
Description
Acute Kidney Disease incidence measured by Kidney Disease Improving Global Outcomes (KDIGO) stage 3 sometime until the 28th day after randomization.
Time Frame
28 days after randomization
Title
Percentage of patients needing dialysis
Description
Percentage of patients needing dialysis sometime until the 28th day.
Time Frame
28 days after randomization
Title
Coagulopathy incidence
Description
Presence of coagulopathy sometime until the 28th day (platelets < 150000 and/or INR >1.5 and/or KPTT > 35 seconds).
Time Frame
28 days after randomization
Title
Mean of C Reactive Protein Levels
Description
Mean of C Reactive Protein Levels on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization
Time Frame
5, 7, 10, 14 and 28 days after randomization
Title
Sequential Organ Failure Assessment (SOFA) scores
Description
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.
Time Frame
5, 7, 10, 14 and 28 days after randomization
Title
Neutrophils/lymphocytes ratio
Description
Neutrophils/lymphocytes ratio on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization.
Time Frame
5, 7, 10, 14 and 28 days after randomization
Other Pre-specified Outcome Measures:
Title
Arrhythmia
Description
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
Time Frame
28 days after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
Centro de Estudos e Pesquisa em Emergencias Clinicas e Terapia Intensiva
City
Curitiba
State/Province
Parana
ZIP/Postal Code
82530200
Country
Brazil

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33907251
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.
Results Reference
derived

Learn more about this trial

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

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