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Randomized Placebo-controlled Trial of Hydroxychloroquine in Outpatient Cases With Coronavirus Disease 2019 (COVID-19) (COALITION-V)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04466540
Recruitment Status : Recruiting
First Posted : July 10, 2020
Last Update Posted : July 10, 2020
Sponsor:
Collaborators:
EMS S/A
Hospital do Coracao
Hospital Israelita Albert Einstein
Hospital Sirio-Libanes
Hospital Moinhos de Vento
Brazilian Research In Intensive Care Network
Information provided by (Responsible Party):
Álvaro Avezum Junior, Hospital Alemão Oswaldo Cruz

Brief Summary:
In December 2019, a group of patients with pneumonia of unknown cause was identified in Wuhan, in the Hubei province, China. Despite the need of target specific therapeutic options for COVID-19, until now there is no proof of effectiveness of any specific intervention. Some limited observational trials and also evidence from randomized trials have shown no benefit of hydroxychloroquine in inpatient context. Thus, studies evaluating interventions in an outpatient setting in non-severe patients can provide important information related to prognosis and safety. In this way, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine in COVID-19 outpatients by means of a Randomized, double-blind, placebo-controlled trial

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Hydroxychloroquine Drug: Placebo Phase 4

Detailed Description:
Pragmatic, double-blind, placebo-controlled randomized parallel-group, two-arm clinical trial (with allocation ratio 1:1), evaluating hydroxychloroquine (800 mg at 1st day, and 400 mg from day 2 to 7) for prevention of hospitalization and respiratory complications in non-hospitalized confirmed or suspected COVID-19 cases. Key inclusion criteria are adults (equal to or greater tahn 18 years) seeking medical care with suspected or confirmed COVID-19, with time between symptoms and inclusion ≤ 07 days, presenting mild symptoms, without indication of hospitalization and at least one risk factor for complication (> 65 years; hypertension; diabetes mellitus; asthma; Chronic Obstructive Pulmonary Disease (COPD) or other chronic lung diseases; smoking; immunosuppression; obesity (Defined as BMI equal to or greater than 30 Kg/m2). Primary endpoint is to assess if the treatment with hydroxychloroquine is able to avoid hospitalization due to a COVID-19-related clinical reason within 30 days of randomization in an outpatient setting. Hospitalization is considered to be hospital stay for a period > 24h or an additional hospitalized calendar day. The primary endpoint is centrally adjudicated by an independent clinical events committee blinded to the assigned treatment groups. Secondary endpoints include uncontrolled asthma after ≥ 5 days of starting study medication; pneumonia; otitis media; fever resolution time; time to improve respiratory symptoms; hospitalization in the Intensive Care Unit; need for orotracheal intubation; mechanical ventilation time; mortality. Safety outcomes will be hypoglycemia; palpitations; reduced visual acuity; diarrhea; anorexia; and emotional lability. The evaluation of the primary outcome (hospitalization within 30 days) will be performed for the included population following the principle of intention-to-treat (ITT), which will consist of all randomized cases. A modified intention-to-treat analysis (mITT), in which cases definitely confirmed as negative for COVID-19 will be excluded, will also be performed.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Pragmatic, double-blind, placebo-controlled randomized parallel-group, two-arm clinical trial (with allocation ratio 1:1)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Randomization (1:1) is generated by a validated software and performed in permuted blocks of size 8. Concealment of the randomization list is maintained through a 24-hour, centralized, automated, internet-based randomization system. Furthermore, as placebo-controlled study, the placebo will have the same structural characteristics as the active drug and will be dispensed in cartridges that do not allow the identification of what is being given
Primary Purpose: Treatment
Official Title: Pragmatic, Double-blind, Placebo-controlled Randomized Clinical Trial, Evaluating Hydroxychloroquine for Prevention of Hospitalization and Respiratory Complications in Non-hospitalized Patients With Confirmed or Probable COVID-19
Actual Study Start Date : May 12, 2020
Estimated Primary Completion Date : August 30, 2020
Estimated Study Completion Date : December 30, 2020


Arm Intervention/treatment
Experimental: Hydroxychloroquine (HCQ)
HCQ group participants will receive a dose of 400mg twice daily (BID) in the first day, and a dose of 400 mg once daily (OD) from the second day of treatment, in a total of 7 days.
Drug: Hydroxychloroquine
Hydroxychloroquine pharmaceutical form will be tablets of 400 mg.

Placebo Comparator: Placebo
The placebo group will follow the same regimen of administration
Drug: Placebo
Hydroxychloroquine placebo




Primary Outcome Measures :
  1. Hospitalization [ Time Frame: 30 days from randomization ]
    To assess if the treatment is able to avoid hospitalization due to a COVID-19-related clinical reason within 30 days of randomization in an outpatient setting. Hospitalization is considered to be hospital stay for a period > 24h or an additional hospitalized calendar day.


Secondary Outcome Measures :
  1. Uncontrolled asthma after ≥ 5 days of starting study medication [ Time Frame: within 30 days from randomization ]
    Affirmative answer in three or four items of the Global Initiative for Asthma (GINA) questionnaire

  2. Pneumonia [ Time Frame: within 30 days from randomization ]
    Defined by clinical-radiological criteria - a history of cough and one or more of the following symptoms: sputum, dyspnea, chest pain, sweating or fever (T> 37.8o C) + Chest CT scan showing ground-glass opacity, focal consolidations or mixed opacities (including reverse halo sign), uni or bilateral

  3. Otitis media [ Time Frame: within 30 days from randomization ]
    Defined by clinical criteria - Fever (T> 37.8o C) and otalgia + bulging of the tympanic membrane

  4. Fever resolution time [ Time Frame: within 30 days from randomization ]
    Day 0 of fever resolution will be defined as the first afebrile day (T <37.5o C) after inclusion in the study followed by at least two consecutive days. The temperature will be obtained through the participant report in the patient's diary

  5. Time to improve respiratory symptoms [ Time Frame: within 30 days from randomization ]
    Time to improve respiratory symptoms (cough, runny nose)

  6. Hospitalization in the Intensive Care Unit [ Time Frame: within 30 days from randomization ]
    Admission to ICU due to clinical reasons related to COVID-19

  7. Need for Orotracheal Intubation [ Time Frame: within 30 days from randomization ]
    Clinical need for Orotracheal Intubation as assessed by the physician responsible for the case

  8. Mechanical Ventilation Time [ Time Frame: within 30 days from randomization ]
    Number of days on mechanical ventilation until extubation or death

  9. Mortality [ Time Frame: within 30 days from randomization ]
    Death due to any cause that occurred within 30 days after inclusion in the study


Other Outcome Measures:
  1. Hypoglycemia [ Time Frame: within 30 days from randomization ]
    Change in the frequency of hypoglycemic episodes in diabetic patients using hypoglycemic medication, perceived by clinical signs or symptoms or measured in a capillary or blood glucose device

  2. Palpitations [ Time Frame: within 30 days from randomization ]
    Presence of cardiac arrhythmias in patients without known history of prolongation of the measure between Q wave and T wave in the heart's electrical cycle (QTc) or pre-existing heart disease;

  3. Reduced visual acuity [ Time Frame: within 30 days from randomization ]
    Change in visual acuity or new diagnosis of retinal disease not previously documented

  4. Diarrhea [ Time Frame: within 30 days from randomization ]
    Change in bowel habit greater than three (3) diarrheal episodes per day during the use of hydroxychloroquine medication and 3 days after its end

  5. Anorexia [ Time Frame: within 30 days from randomization ]
    Change in appetite during medication use hydroxychloroquine and 3 days after the end of treatment

  6. Emotional lability [ Time Frame: within 30 days from randomization ]
    Perception of change in emotional lability (mood swings) during hydroxychloroquine use and 3 days after the end of treatment

  7. Time to hospitalization after randomization [ Time Frame: within 30 days from randomization ]
    Time from randomization to hospitalization

  8. Assessment of the patient clinical status at the time of hospitalization [ Time Frame: within 30 days from randomization ]
    Clinical and vital signs assessed when admitted to hospital



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

It will be considered eligible those adults (equal to or greater than 18 years) seeking medical care with suspected or confirmed COVID-19, with time between symptoms and inclusion ≤ 07 days, presenting mild symptoms, without indication of hospitalization and at least 1 risk factor for complication:

  1. > 65 years;
  2. Hypertension;
  3. Diabetes mellitus;
  4. Asthma;
  5. COPD or other chronic lung diseases;
  6. Smoking;
  7. Immunosuppression;
  8. Obesity (Defined as BMI equal to or greater than 30 Kg/m2).

Exclusion Criteria:

  1. Patients under 18 years old;
  2. Hospitalization at the first medical care;
  3. Positive test for influenza at the first medical care;
  4. Known hypersensitivity to hydroxychloroquine / chloroquine;
  5. Previous diagnosis of retinopathy or macular degeneration;
  6. Previous diagnosis of Long QT-syndrome, history of sudden death in close family members (parents and siblings), decompensated heart failure, unstable coronary artery disease, use of anti-arrhythmic drugs or other drugs that can increase the hydroxychloroquine bioavailability or enhance its effect;
  7. Evidence of known liver disease, reported by the patient;
  8. Evidence of known chronic kidney disease, reported by the patient;
  9. Patients with pancreatitis;
  10. Baseline ECG with QTc interval ≥ 480ms;
  11. Chronic use of hydroxychloroquine/chloroquine for other reasons;
  12. Pregnancy.

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): NCT04466540


Contacts
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Contact: Dayane Vilanova +55(11)3549-0729 dvilanova@haoc.com.br
Contact: Haliton Alves de Oliveira Junior, Ph.D +55(11)3549-0581 haoliveira@haoc.com.br

Locations
Show Show 69 study locations
Sponsors and Collaborators
Hospital Alemão Oswaldo Cruz
EMS S/A
Hospital do Coracao
Hospital Israelita Albert Einstein
Hospital Sirio-Libanes
Hospital Moinhos de Vento
Brazilian Research In Intensive Care Network
Investigators
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Principal Investigator: Álvaro Avezum, Ph.D International Research Center - Hospital Alemão Oswaldo Cruz
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Responsible Party: Álvaro Avezum Junior, Research Manager - International Research Center, Hospital Alemão Oswaldo Cruz
ClinicalTrials.gov Identifier: NCT04466540    
Other Study ID Numbers: 30415320.8.1001.0070
First Posted: July 10, 2020    Key Record Dates
Last Update Posted: July 10, 2020
Last Verified: July 2020
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
Keywords provided by Álvaro Avezum Junior, Hospital Alemão Oswaldo Cruz:
COVID-19
Severe Acute Respiratory Syndrome - Coronavirus-2
Hydroxychloroquine
COALITION Brazil V 2019
Outpatients
Additional relevant MeSH terms:
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Hydroxychloroquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents