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

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ClinicalTrials.gov Identifier: NCT04420247
Recruitment Status : Completed
First Posted : June 9, 2020
Last Update Posted : May 12, 2021
Sponsor:
Information provided by (Responsible Party):
ALVARO REA-NETO, MD, Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva

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.

Condition or disease Intervention/treatment Phase
COVID COVID-19 SARS-CoV 2 Coronavirus Corona Virus Infection Drug: Chloroquine Drug: Hydroxychloroquine Other: standard care Phase 3

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)

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 142 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 16, 2020
Actual Primary Completion Date : August 20, 2020
Actual Study Completion Date : September 3, 2020


Arm Intervention/treatment
Experimental: Intervention

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.

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

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

Active Comparator: Control
Standard treatment available and recomended by the Brazilian Guidelines for COVID-19.
Other: standard care
Standard Care according to Brazilian Guidelines for treating COVID-19




Primary Outcome Measures :
  1. World Health Organization (WHO) 9-levels ordinal scale (from 0-8) [ Time Frame: 14 days after randomization ]
    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 :
  1. World Health Organization (WHO) 9-levels ordinal scale (from 0-8) [ Time Frame: 5, 7, 10 and 28 days after randomization ]
    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.

  2. Mortality [ Time Frame: 28 days after randomization ]
    All-cause mortality at 28 days after randomization

  3. Ventilation free days [ Time Frame: 28 days after randomization ]
    Number of days without need of Mechanical Ventilation at 28 days after randomization

  4. ICU Lenght of Stay [ Time Frame: 28 days after randomization ]
    ICU Lenght of Stay on survivors at 28 days after randomization

  5. Hospital Lenght of Stay [ Time Frame: 28 days after randomization ]
    Hospital Lenght of Stay on survivors at 28 days after randomization

  6. Acute Kidney Disease incidence [ Time Frame: 28 days after randomization ]
    Acute Kidney Disease incidence measured by Kidney Disease Improving Global Outcomes (KDIGO) stage 3 sometime until the 28th day after randomization.

  7. Percentage of patients needing dialysis [ Time Frame: 28 days after randomization ]
    Percentage of patients needing dialysis sometime until the 28th day.

  8. Coagulopathy incidence [ Time Frame: 28 days after randomization ]
    Presence of coagulopathy sometime until the 28th day (platelets < 150000 and/or INR >1.5 and/or KPTT > 35 seconds).

  9. Mean of C Reactive Protein Levels [ Time Frame: 5, 7, 10, 14 and 28 days after randomization ]
    Mean of C Reactive Protein Levels on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization

  10. Sequential Organ Failure Assessment (SOFA) scores [ Time Frame: 5, 7, 10, 14 and 28 days after randomization ]
    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.

  11. Neutrophils/lymphocytes ratio [ Time Frame: 5, 7, 10, 14 and 28 days after randomization ]
    Neutrophils/lymphocytes ratio on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization.


Other Outcome Measures:
  1. Arrhythmia [ Time Frame: 28 days after randomization ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04420247


Locations
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Brazil
Centro de Estudos e Pesquisa em Emergencias Clinicas e Terapia Intensiva
Curitiba, Parana, Brazil, 82530200
Sponsors and Collaborators
Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: ALVARO REA-NETO, MD, Director of the Reseach Center, Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva
ClinicalTrials.gov Identifier: NCT04420247    
Other Study ID Numbers: CLOROTRIAL
First Posted: June 9, 2020    Key Record Dates
Last Update Posted: May 12, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by ALVARO REA-NETO, MD, Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva:
VIRAL PNEUMONIA
CORONAVIRUS
COVID-19
COVID
SARS-COV-2
Additional relevant MeSH terms:
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COVID-19
Pneumonia
Coronavirus Infections
Respiratory Tract Infections
Infections
Pneumonia, Viral
Virus Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Hydroxychloroquine
Chloroquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents
Amebicides