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Safety and Efficacy of Hydroxychloroquine Associated With Azithromycin in SARS-CoV2 Virus (Coalition Covid-19 Brasil II)

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ClinicalTrials.gov Identifier: NCT04321278
Recruitment Status : Recruiting
First Posted : March 25, 2020
Last Update Posted : May 27, 2020
Sponsor:
Collaborators:
EMS
Hospital do Coracao
Hospital Sirio-Libanes
Brazilian Research In Intensive Care Network
Information provided by (Responsible Party):
Hospital Israelita Albert Einstein

Brief Summary:
The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract. Around 20% of those infected have severe pneumonia and currently there is no specific or effective therapy to treat this disease. Therapeutic options using malaria drugs chloroquine and hydroxychloroquine have shown promising results in vitro and in vivo test. But those efforts have not involved large, carefully-conducted controlled studies that would provide the global medical community the proof that these drugs work on a significant scale. In this way, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in patients hospitalized with pneumonia by SARS-CoV2 virus.

Condition or disease Intervention/treatment Phase
Coronavirus Infections Pneumonia, Viral Drug: Hydroxychloroquine + azithromycin Drug: Hydroxychloroquine Phase 3

Detailed Description:
The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract that is now spreading to several countries in the world, including Brazil. Mortality rates after infection are higher in adults over 60 and with a history of comorbidities. The most serious patients need care in intensive care units (ICU). Most of the time they depend on mechanical ventilation support due to acute respiratory distress syndrome (ARDS). Infection rates are higher than the capacity for intensive care, which represents a serious problem in medical care. Around 20% of those infected have severe pneumonia and so far it does not have a specific therapy, or even, an effective clinical management. Therapeutic options using malaria drugs chloroquine and hydroxychloroquine have shown promising results in vitro and in vivo test. A recent, small, non-randomized study with hydroxychloroquine in 36 patients infected with SARS-Cov-2 proved to be promising in the ability to reset the viral load in 6 days after starting treatment. Thus, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in the clinical evolution by the ordinal scale of 6 points in adult patients hospitalized with pneumonia caused by infection by the SARS-CoV2 virus in Brazil.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 440 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
  1. Intervention Group: Hydroxychloroquine + azithromycin. After randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] + azithromycin [500mg 1x/day]) for 10 days. Standard treatment is according to the treatment protocol for 2019-nCoV infection.
  2. Active Control Group: Hydroxychloroquine. After randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] for 10 days. Standard treatment is according to the treatment protocol for 2019-nCoV infection.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of the Safety and Clinical Efficacy of Hydroxychloroquine Associated With Azithromycin in Patients With Pneumonia Caused by Infection by the SARS-CoV2 Virus - Coalition COVID-19 Brasil II - SEVERE - Patients
Actual Study Start Date : March 28, 2020
Estimated Primary Completion Date : August 30, 2020
Estimated Study Completion Date : August 30, 2020


Arm Intervention/treatment
Experimental: Hydroxychloroquine + azithromycin
Hydroxychloroquine [400mg 2x/day, 12/12h] + azithromycin [500mg 1x/day]
Drug: Hydroxychloroquine + azithromycin
Intervention Group: Hydroxychloroquine + azithromycin. After randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] + azithromycin [500mg 1x/day]) for 10 days. Standard treatment is according to the treatment protocol for 2019-nCoV infection.

Active Comparator: Hydroxychloroquine
Hydroxychloroquine [400mg 2x/day, 12/12h]
Drug: Hydroxychloroquine
Active Control Group: Hydroxychloroquine. After randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] for 10 days. Standard treatment is according to the treatment protocol for 2019-nCoV infection.




Primary Outcome Measures :
  1. Evaluation of the clinical status [ Time Frame: 15 days after randomization ]
    Evaluation of the clinical status of patients on the 15th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score)


Secondary Outcome Measures :
  1. All-cause mortality [ Time Frame: 29 days after randomization ]
    All-cause mortality rates at 29 days after randomization

  2. Evaluation of the clinical status [ Time Frame: 7 and 29 days after randomization ]
    Evaluation of the clinical status of patients on the 7th and 29th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score)

  3. Number of days free from mechanical ventilation [ Time Frame: 29 days after randomization ]
    Number of days free from mechanical ventilation at 29 days after randomization

  4. Duration of mechanical ventilation [ Time Frame: 29 days after randomization ]
    Number of days that the patient was on mechanical ventilation after randomization

  5. Duration of hospitalization [ Time Frame: 29 days after randomization ]
    Length of hospital stay on survivors

  6. Other secondary infections [ Time Frame: 29 days after randomization ]
    Presence of other secondary infections

  7. Time from treatment start to death [ Time Frame: 29 days after randomization ]
    Time from treatment start to death

  8. Medium and long-term outcomes of SARS-CoV2 infection on morbimortality, daily life activities, mental health, and quality of life [ Time Frame: 3, 6, 9 and 12 months ]
    Morbimortality, daily life activities, mental health, and quality of life

  9. Assess whether the tested therapies may be affected by leucocyte phenotype [ Time Frame: Baseline ]
    Leucocyte transcriptome


Other Outcome Measures:
  1. QT interval prolongation [ Time Frame: 29 days after randomization ]
    Occurrence of QT interval prolongation

  2. Gastrointestinal intolerance [ Time Frame: 29 days after randomization ]
    Occurrence of gastrointestinal intolerance

  3. Laboratory abnormalities [ Time Frame: 29 days after randomization ]
    Occurrence of laboratory hematimetric parameters, creatinine and bilirubin

  4. Adverse events [ Time Frame: 29 days after randomization ]
    Occurrence of adverse events related to the use of the investigational products



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:

  1. Males and females aged > 18 years;
  2. Suspected or confirmed infection by SARS-CoV2;

Presenting with one of the following:

  • Need for oxygen supplementation > 4 L/min, or
  • Need for high-flow nasal canula, or
  • Need for non-invasive ventilation, or
  • Need for mechanical ventilation.

Exclusion Criteria:

  1. Refusal to provide written informed consent (either the patient or a legal representative);
  2. Hypersensitivity to any of the drugs used in the study (Azithromycin or Hydroxychloroquine);
  3. Patients with more than 48 hours of prior study medication use;
  4. Patients with onset of symptoms longer than 14 days;
  5. Patients with long QT syndrome or severe ventricular arrhythmias, not protected by an implantable cardioverter defibrillators (ICD).;
  6. QTc>= 480ms;
  7. Do not resuscitate order or exclusive palliative care;
  8. Patients with liver disease or cirrhosis or abnormal liver enzyme tests above three times the upper limit values (alanine aminotransferase -ALT and aspartate aminotransferase - AST);
  9. Patients with known retinopathy or macular degeneration;
  10. Patients with history of pancreatitis;
  11. Patients with concomitant use of medications that alter the absorption or excretion of azithromycin or hydroxychloroquine;
  12. Breastfeeding women;
  13. 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): NCT04321278


Contacts
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Contact: ARO-HIAE Academic Research Organization HIAE +55 (11) 2151-1233 aro.clinicaltrials@einstein.br
Contact: Henrique Fonseca, PhD +55 (11) 2151-1233 henrique.fonseca@einstein.br

Locations
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Sponsors and Collaborators
Hospital Israelita Albert Einstein
EMS
Hospital do Coracao
Hospital Sirio-Libanes
Brazilian Research In Intensive Care Network
Investigators
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Study Director: Otávio Berwanger, PhD Hospital Israelita Albert Einstein
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Responsible Party: Hospital Israelita Albert Einstein
ClinicalTrials.gov Identifier: NCT04321278    
Other Study ID Numbers: 30155020.5.1001.0071
First Posted: March 25, 2020    Key Record Dates
Last Update Posted: May 27, 2020
Last Verified: March 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
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Hospital Israelita Albert Einstein:
SARS-CoV2 virus
2019-nCOV
COVID-19
hydroxychloroquine
azithromycin
Additional relevant MeSH terms:
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Infection
Coronavirus Infections
Severe Acute Respiratory Syndrome
Pneumonia, Viral
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Azithromycin
Hydroxychloroquine
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents