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

Sponsor
Hospital Israelita Albert Einstein (Other)
Overall Status
Completed
CT.gov ID
NCT04321278
Collaborator
EMS (Industry), Hospital do Coracao (Other), Hospital Sirio-Libanes (Other), Brazilian Research In Intensive Care Network (Other)
440
Enrollment
58
Locations
2
Arms
2.6
Actual Duration (Months)
7.6
Patients Per Site
3
Patients Per Site Per Month

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
Actual Enrollment :
440 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
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 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.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 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 :
Mar 28, 2020
Actual Primary Completion Date :
Jun 14, 2020
Actual Study Completion Date :
Jun 14, 2020

Arms and Interventions

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.
Other Names:
  • HCQ+AZI

    		•
    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.
    Other Names:
  • HCQ

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Evaluation of the clinical status [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 [29 days after randomization]

      All-cause mortality rates at 29 days after randomization

    2. Evaluation of the clinical status [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 [29 days after randomization]

      Number of days free from mechanical ventilation at 29 days after randomization

    4. Duration of mechanical ventilation [29 days after randomization]

      Number of days that the patient was on mechanical ventilation after randomization

    5. Duration of hospitalization [29 days after randomization]

      Length of hospital stay on survivors

    6. Other secondary infections [29 days after randomization]

      Presence of other secondary infections

    7. Time from treatment start to death [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 [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 [Baseline]

      Leucocyte transcriptome

    Other Outcome Measures

    1. QT interval prolongation [29 days after randomization]

      Occurrence of QT interval prolongation

    2. Gastrointestinal intolerance [29 days after randomization]

      Occurrence of gastrointestinal intolerance

    3. Laboratory abnormalities [29 days after randomization]

      Occurrence of laboratory hematimetric parameters, creatinine and bilirubin

    4. Adverse events [29 days after randomization]

      Occurrence of adverse events related to the use of the investigational products

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hospital de Urgência e Emergência de Rio Branco Rio Branco AC Brazil
    2 Hospital e Clínica São Roque Ipiaú BA Brazil
    3 Hospital da Cidade Salvador BA Brazil
    4 Hospital Maternidade São Vicente de Paulo Barbalha CE Brazil
    5 Hospital de Messejana Dr. Carlos Alberto Studart Gomes Fortaleza CE Brazil
    6 Hospital Unimed Cariri Juazeiro Do Norte CE Brazil
    7 Hospital Brasilia Brasilia DF Brazil
    8 Hospital Estadual Jayme dos Santos Neves Serra ES Brazil
    9 Hospital Evangélico de Vila Velha Vila Velha ES Brazil
    10 Secretaria de Estado de Saúde de Goias Goiânia GO Brazil
    11 Santa Casa de Misericórdia de Belo Horizonte Santa Casa de BH Belo Horizonte MG Brazil
    12 Hospital Santa Paula Passos MG Brazil
    13 Santa Casa da Misericordia - UTI (São João Del Rey) São João Del Rei MG Brazil
    14 Hospital Maternidade E Pronto Socorro Santa Lucia Ltda Poços De Caldas Minas Gerais Brazil
    15 Universidade Estadual de Londrina Londrina Paraná Brazil
    16 Hospital Adventista de Belém Belém Pará Brazil
    17 Hospital Adventista de Belem Belem PA Brazil
    18 Procape - Pronto S.Cardiologico de Pe.Prof.Luiz Tavares- Recife PE Brazil
    19 Liga Paranaense de Combate ao Câncer Curitiba PR Brazil
    20 Hospital Giselda Trigueiro Natal Rio Grande Do Norte Brazil
    21 Hospital Moinhos de Vento Porto Alegre Rio Grande Do Sul Brazil
    22 Irmandade da Santa Casa de Misericordia de Porto Alegre Porto Alegre Rio Grande Do Sul Brazil
    23 Hospital Naval Marcílio Dias Rio de Janeiro RJ Brazil
    24 Hospital São Lucas Rio De Janeiro RJ Brazil
    25 Hospital Maternidade PROMATER Natal RN Brazil
    26 Associação Dr. Bartholomeu Tacchini Bento Gonçalves RS Brazil
    27 Hospital Geral de Caxias do Sul Caxias Do Sul RS Brazil
    28 Hospital Bruno Born Lajeado RS Brazil
    29 Hospital São Vicente de Paulo Passo Fundo RS Brazil
    30 Maestri E Kormann Consultoria Medico-Cientifica Blumenau Santa Catarina Brazil
    31 Sociedade Literaria e Caritativa Santo Agostinho Criciúma Santa Catarina Brazil
    32 Hospital Nereu Ramos Florianópolis SC Brazil
    33 Hospital Universitário Polydoro Ernani de São Thiago/HU - UFSC Florianópolis SC Brazil
    34 Centro Hospitalar Unimed Joinville SC Brazil
    35 Hospital Dona Helena Joinville SC Brazil
    36 Hospital Municipal Sao Jose Joinville SC Brazil
    37 Hospital Regional Hans Dieter Schmidt Joinville SC Brazil
    38 Faculdade de Medicina de Botucatu Botucatu SP Brazil
    39 nstituto de Pesquisa Clínica de Campinas Campinas SP Brazil
    40 Fundação do ABC (Hospital Estadual Mário Covas) Santo André SP Brazil
    41 AC Camargo Cancer Center - Fundação Antonio Prudente São Paulo SP Brazil
    42 Casa de Saude Santa Marcelina São Paulo SP Brazil
    43 Hospital Alemão Oswaldo Cruz São Paulo SP Brazil
    44 Hospital Moriah São Paulo SP Brazil
    45 Hospital Nove de Julho São Paulo SP Brazil
    46 Hospital Santa Paula São Paulo SP Brazil
    47 Hospital São Camilo Pompeia São Paulo SP Brazil
    48 Fundação Pio XII Barretos São Paulo Brazil
    49 Santa Casa de Misericordia de Votuporanga Votuporanga São Paulo Brazil
    50 Hospital Israelita Albert Einstein São Paulo Brazil 05652-900
    51 A Beneficência Portuguesa de São Paulo - BP São Paulo Brazil
    52 Associacao Beneficente Siria São Paulo Brazil
    53 Hospital Vila Santa Catarina São Paulo Brazil
    54 Real e Benemérita Associação Portuguesa de Beneficência/SP - 1 São Paulo Brazil
    55 Secretaria de Saúde do Estado de São Paulo São Paulo Brazil
    56 Serv Social da Industria do papel, papelão e cortiça do estado de SP São Paulo Brazil
    57 Sociedade Beneficente de Senhoras Hospital Sírio-Libanês São Paulo Brazil
    58 Universidade Federal de São Paulo São Paulo Brazil

    Sponsors and Collaborators

    • Hospital Israelita Albert Einstein
    • EMS
    • Hospital do Coracao
    • Hospital Sirio-Libanes
    • Brazilian Research In Intensive Care Network

    Investigators

    • Study Director: Otávio Berwanger, PhD, Hospital Israelita Albert Einstein

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hospital Israelita Albert Einstein
    ClinicalTrials.gov Identifier:
    NCT04321278
    Other Study ID Numbers:
    • 30155020.5.1001.0071
    First Posted:
    Mar 25, 2020
    Last Update Posted:
    Jan 20, 2021
    Last Verified:
    Mar 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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:
    Infections
    COVID-19
    Pneumonia
    Coronavirus Infections
    Pneumonia, Viral
    Azithromycin
    Hydroxychloroquine

    Study Results

    No Results Posted as of Jan 20, 2021