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

Primary Purpose

Coronavirus Infections, Pneumonia, Viral

Status
Completed
Phase
Phase 3
Locations
Brazil
Study Type
Interventional
Intervention
Hydroxychloroquine + azithromycin
Hydroxychloroquine
Sponsored by
Hospital Israelita Albert Einstein
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronavirus Infections focused on measuring SARS-CoV2 virus, 2019-nCOV, COVID-19, hydroxychloroquine, azithromycin

Eligibility Criteria

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

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

Sites / Locations

  • Hospital de Urgência e Emergência de Rio Branco
  • Hospital e Clínica São Roque
  • Hospital da Cidade
  • Hospital Maternidade São Vicente de Paulo
  • Hospital de Messejana Dr. Carlos Alberto Studart Gomes
  • Hospital Unimed Cariri
  • Hospital Brasilia
  • Hospital Estadual Jayme dos Santos Neves
  • Hospital Evangélico de Vila Velha
  • Secretaria de Estado de Saúde de Goias
  • Santa Casa de Misericórdia de Belo Horizonte Santa Casa de BH
  • Hospital Santa Paula
  • Santa Casa da Misericordia - UTI (São João Del Rey)
  • Hospital Maternidade E Pronto Socorro Santa Lucia Ltda
  • Universidade Estadual de Londrina
  • Hospital Adventista de Belém
  • Hospital Adventista de Belem
  • Procape - Pronto S.Cardiologico de Pe.Prof.Luiz Tavares-
  • Liga Paranaense de Combate ao Câncer
  • Hospital Giselda Trigueiro
  • Hospital Moinhos de Vento
  • Irmandade da Santa Casa de Misericordia de Porto Alegre
  • Hospital Naval Marcílio Dias
  • Hospital São Lucas
  • Hospital Maternidade PROMATER
  • Associação Dr. Bartholomeu Tacchini
  • Hospital Geral de Caxias do Sul
  • Hospital Bruno Born
  • Hospital São Vicente de Paulo
  • Maestri E Kormann Consultoria Medico-Cientifica
  • Sociedade Literaria e Caritativa Santo Agostinho
  • Hospital Nereu Ramos
  • Hospital Universitário Polydoro Ernani de São Thiago/HU - UFSC
  • Centro Hospitalar Unimed
  • Hospital Dona Helena
  • Hospital Municipal Sao Jose
  • Hospital Regional Hans Dieter Schmidt
  • Faculdade de Medicina de Botucatu
  • nstituto de Pesquisa Clínica de Campinas
  • Fundação do ABC (Hospital Estadual Mário Covas)
  • AC Camargo Cancer Center - Fundação Antonio Prudente
  • Casa de Saude Santa Marcelina
  • Hospital Alemão Oswaldo Cruz
  • Hospital Moriah
  • Hospital Nove de Julho
  • Hospital Santa Paula
  • Hospital São Camilo Pompeia
  • Fundação Pio XII
  • Santa Casa de Misericordia de Votuporanga
  • Hospital Israelita Albert Einstein
  • A Beneficência Portuguesa de São Paulo - BP
  • Associacao Beneficente Siria
  • Hospital Vila Santa Catarina
  • Real e Benemérita Associação Portuguesa de Beneficência/SP - 1
  • Secretaria de Saúde do Estado de São Paulo
  • Serv Social da Industria do papel, papelão e cortiça do estado de SP
  • Sociedade Beneficente de Senhoras Hospital Sírio-Libanês
  • Universidade Federal de São Paulo

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Hydroxychloroquine + azithromycin

Hydroxychloroquine

Arm Description

Hydroxychloroquine [400mg 2x/day, 12/12h] + azithromycin [500mg 1x/day]

Hydroxychloroquine [400mg 2x/day, 12/12h]

Outcomes

Primary Outcome Measures

Evaluation of the clinical status
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

All-cause mortality
All-cause mortality rates at 29 days after randomization
Evaluation of the clinical status
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)
Number of days free from mechanical ventilation
Number of days free from mechanical ventilation at 29 days after randomization
Duration of mechanical ventilation
Number of days that the patient was on mechanical ventilation after randomization
Duration of hospitalization
Length of hospital stay on survivors
Other secondary infections
Presence of other secondary infections
Time from treatment start to death
Time from treatment start to death
Medium and long-term outcomes of SARS-CoV2 infection on morbimortality, daily life activities, mental health, and quality of life
Morbimortality, daily life activities, mental health, and quality of life
Assess whether the tested therapies may be affected by leucocyte phenotype
Leucocyte transcriptome

Full Information

First Posted
March 23, 2020
Last Updated
January 15, 2021
Sponsor
Hospital Israelita Albert Einstein
Collaborators
EMS, Hospital do Coracao, Hospital Sirio-Libanes, Brazilian Research In Intensive Care Network
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1. Study Identification

Unique Protocol Identification Number
NCT04321278
Brief Title
Safety and Efficacy of Hydroxychloroquine Associated With Azithromycin in SARS-CoV2 Virus (Coalition Covid-19 Brasil II)
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
March 28, 2020 (Actual)
Primary Completion Date
June 14, 2020 (Actual)
Study Completion Date
June 14, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital Israelita Albert Einstein
Collaborators
EMS, Hospital do Coracao, Hospital Sirio-Libanes, Brazilian Research In Intensive Care Network

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
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronavirus Infections, Pneumonia, Viral
Keywords
SARS-CoV2 virus, 2019-nCOV, COVID-19, hydroxychloroquine, azithromycin

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Hydroxychloroquine + azithromycin
Arm Type
Experimental
Arm Description
Hydroxychloroquine [400mg 2x/day, 12/12h] + azithromycin [500mg 1x/day]
Arm Title
Hydroxychloroquine
Arm Type
Active Comparator
Arm Description
Hydroxychloroquine [400mg 2x/day, 12/12h]
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine + azithromycin
Other Intervention Name(s)
HCQ+AZI
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Other Intervention Name(s)
HCQ
Intervention Description
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 Measure Information:
Title
Evaluation of the clinical status
Description
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)
Time Frame
15 days after randomization
Secondary Outcome Measure Information:
Title
All-cause mortality
Description
All-cause mortality rates at 29 days after randomization
Time Frame
29 days after randomization
Title
Evaluation of the clinical status
Description
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)
Time Frame
7 and 29 days after randomization
Title
Number of days free from mechanical ventilation
Description
Number of days free from mechanical ventilation at 29 days after randomization
Time Frame
29 days after randomization
Title
Duration of mechanical ventilation
Description
Number of days that the patient was on mechanical ventilation after randomization
Time Frame
29 days after randomization
Title
Duration of hospitalization
Description
Length of hospital stay on survivors
Time Frame
29 days after randomization
Title
Other secondary infections
Description
Presence of other secondary infections
Time Frame
29 days after randomization
Title
Time from treatment start to death
Description
Time from treatment start to death
Time Frame
29 days after randomization
Title
Medium and long-term outcomes of SARS-CoV2 infection on morbimortality, daily life activities, mental health, and quality of life
Description
Morbimortality, daily life activities, mental health, and quality of life
Time Frame
3, 6, 9 and 12 months
Title
Assess whether the tested therapies may be affected by leucocyte phenotype
Description
Leucocyte transcriptome
Time Frame
Baseline
Other Pre-specified Outcome Measures:
Title
QT interval prolongation
Description
Occurrence of QT interval prolongation
Time Frame
29 days after randomization
Title
Gastrointestinal intolerance
Description
Occurrence of gastrointestinal intolerance
Time Frame
29 days after randomization
Title
Laboratory abnormalities
Description
Occurrence of laboratory hematimetric parameters, creatinine and bilirubin
Time Frame
29 days after randomization
Title
Adverse events
Description
Occurrence of adverse events related to the use of the investigational products
Time Frame
29 days after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Males and females aged > 18 years; 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: Refusal to provide written informed consent (either the patient or a legal representative); Hypersensitivity to any of the drugs used in the study (Azithromycin or Hydroxychloroquine); Patients with more than 48 hours of prior study medication use; Patients with onset of symptoms longer than 14 days; Patients with long QT syndrome or severe ventricular arrhythmias, not protected by an implantable cardioverter defibrillators (ICD).; QTc>= 480ms; Do not resuscitate order or exclusive palliative care; 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); Patients with known retinopathy or macular degeneration; Patients with history of pancreatitis; Patients with concomitant use of medications that alter the absorption or excretion of azithromycin or hydroxychloroquine; Breastfeeding women; Pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Otávio Berwanger, PhD
Organizational Affiliation
Hospital Israelita Albert Einstein
Official's Role
Study Director
Facility Information:
Facility Name
Hospital de Urgência e Emergência de Rio Branco
City
Rio Branco
State/Province
AC
Country
Brazil
Facility Name
Hospital e Clínica São Roque
City
Ipiaú
State/Province
BA
Country
Brazil
Facility Name
Hospital da Cidade
City
Salvador
State/Province
BA
Country
Brazil
Facility Name
Hospital Maternidade São Vicente de Paulo
City
Barbalha
State/Province
CE
Country
Brazil
Facility Name
Hospital de Messejana Dr. Carlos Alberto Studart Gomes
City
Fortaleza
State/Province
CE
Country
Brazil
Facility Name
Hospital Unimed Cariri
City
Juazeiro Do Norte
State/Province
CE
Country
Brazil
Facility Name
Hospital Brasilia
City
Brasilia
State/Province
DF
Country
Brazil
Facility Name
Hospital Estadual Jayme dos Santos Neves
City
Serra
State/Province
ES
Country
Brazil
Facility Name
Hospital Evangélico de Vila Velha
City
Vila Velha
State/Province
ES
Country
Brazil
Facility Name
Secretaria de Estado de Saúde de Goias
City
Goiânia
State/Province
GO
Country
Brazil
Facility Name
Santa Casa de Misericórdia de Belo Horizonte Santa Casa de BH
City
Belo Horizonte
State/Province
MG
Country
Brazil
Facility Name
Hospital Santa Paula
City
Passos
State/Province
MG
Country
Brazil
Facility Name
Santa Casa da Misericordia - UTI (São João Del Rey)
City
São João Del Rei
State/Province
MG
Country
Brazil
Facility Name
Hospital Maternidade E Pronto Socorro Santa Lucia Ltda
City
Poços De Caldas
State/Province
Minas Gerais
Country
Brazil
Facility Name
Universidade Estadual de Londrina
City
Londrina
State/Province
Paraná
Country
Brazil
Facility Name
Hospital Adventista de Belém
City
Belém
State/Province
Pará
Country
Brazil
Facility Name
Hospital Adventista de Belem
City
Belem
State/Province
PA
Country
Brazil
Facility Name
Procape - Pronto S.Cardiologico de Pe.Prof.Luiz Tavares-
City
Recife
State/Province
PE
Country
Brazil
Facility Name
Liga Paranaense de Combate ao Câncer
City
Curitiba
State/Province
PR
Country
Brazil
Facility Name
Hospital Giselda Trigueiro
City
Natal
State/Province
Rio Grande Do Norte
Country
Brazil
Facility Name
Hospital Moinhos de Vento
City
Porto Alegre
State/Province
Rio Grande Do Sul
Country
Brazil
Facility Name
Irmandade da Santa Casa de Misericordia de Porto Alegre
City
Porto Alegre
State/Province
Rio Grande Do Sul
Country
Brazil
Facility Name
Hospital Naval Marcílio Dias
City
Rio de Janeiro
State/Province
RJ
Country
Brazil
Facility Name
Hospital São Lucas
City
Rio De Janeiro
State/Province
RJ
Country
Brazil
Facility Name
Hospital Maternidade PROMATER
City
Natal
State/Province
RN
Country
Brazil
Facility Name
Associação Dr. Bartholomeu Tacchini
City
Bento Gonçalves
State/Province
RS
Country
Brazil
Facility Name
Hospital Geral de Caxias do Sul
City
Caxias Do Sul
State/Province
RS
Country
Brazil
Facility Name
Hospital Bruno Born
City
Lajeado
State/Province
RS
Country
Brazil
Facility Name
Hospital São Vicente de Paulo
City
Passo Fundo
State/Province
RS
Country
Brazil
Facility Name
Maestri E Kormann Consultoria Medico-Cientifica
City
Blumenau
State/Province
Santa Catarina
Country
Brazil
Facility Name
Sociedade Literaria e Caritativa Santo Agostinho
City
Criciúma
State/Province
Santa Catarina
Country
Brazil
Facility Name
Hospital Nereu Ramos
City
Florianópolis
State/Province
SC
Country
Brazil
Facility Name
Hospital Universitário Polydoro Ernani de São Thiago/HU - UFSC
City
Florianópolis
State/Province
SC
Country
Brazil
Facility Name
Centro Hospitalar Unimed
City
Joinville
State/Province
SC
Country
Brazil
Facility Name
Hospital Dona Helena
City
Joinville
State/Province
SC
Country
Brazil
Facility Name
Hospital Municipal Sao Jose
City
Joinville
State/Province
SC
Country
Brazil
Facility Name
Hospital Regional Hans Dieter Schmidt
City
Joinville
State/Province
SC
Country
Brazil
Facility Name
Faculdade de Medicina de Botucatu
City
Botucatu
State/Province
SP
Country
Brazil
Facility Name
nstituto de Pesquisa Clínica de Campinas
City
Campinas
State/Province
SP
Country
Brazil
Facility Name
Fundação do ABC (Hospital Estadual Mário Covas)
City
Santo André
State/Province
SP
Country
Brazil
Facility Name
AC Camargo Cancer Center - Fundação Antonio Prudente
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Casa de Saude Santa Marcelina
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Hospital Alemão Oswaldo Cruz
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Hospital Moriah
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Hospital Nove de Julho
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Hospital Santa Paula
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Hospital São Camilo Pompeia
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Fundação Pio XII
City
Barretos
State/Province
São Paulo
Country
Brazil
Facility Name
Santa Casa de Misericordia de Votuporanga
City
Votuporanga
State/Province
São Paulo
Country
Brazil
Facility Name
Hospital Israelita Albert Einstein
City
São Paulo
ZIP/Postal Code
05652-900
Country
Brazil
Facility Name
A Beneficência Portuguesa de São Paulo - BP
City
São Paulo
Country
Brazil
Facility Name
Associacao Beneficente Siria
City
São Paulo
Country
Brazil
Facility Name
Hospital Vila Santa Catarina
City
São Paulo
Country
Brazil
Facility Name
Real e Benemérita Associação Portuguesa de Beneficência/SP - 1
City
São Paulo
Country
Brazil
Facility Name
Secretaria de Saúde do Estado de São Paulo
City
São Paulo
Country
Brazil
Facility Name
Serv Social da Industria do papel, papelão e cortiça do estado de SP
City
São Paulo
Country
Brazil
Facility Name
Sociedade Beneficente de Senhoras Hospital Sírio-Libanês
City
São Paulo
Country
Brazil
Facility Name
Universidade Federal de São Paulo
City
São Paulo
Country
Brazil

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32896292
Citation
Furtado RHM, Berwanger O, Fonseca HA, Correa TD, Ferraz LR, Lapa MG, Zampieri FG, Veiga VC, Azevedo LCP, Rosa RG, Lopes RD, Avezum A, Manoel ALO, Piza FMT, Martins PA, Lisboa TC, Pereira AJ, Olivato GB, Dantas VCS, Milan EP, Gebara OCE, Amazonas RB, Oliveira MB, Soares RVP, Moia DDF, Piano LPA, Castilho K, Momesso RGRAP, Schettino GPP, Rizzo LV, Neto AS, Machado FR, Cavalcanti AB; COALITION COVID-19 Brazil II Investigators. Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial. Lancet. 2020 Oct 3;396(10256):959-967. doi: 10.1016/S0140-6736(20)31862-6. Epub 2020 Sep 5.
Results Reference
derived
PubMed Identifier
32386744
Citation
Lasheras I, Santabarbara J. Use of antimalarial drugs in the treatment of COVID-19: A window of opportunity? Med Clin (Barc). 2020 Jul 10;155(1):23-25. doi: 10.1016/j.medcli.2020.04.004. Epub 2020 Apr 22. No abstract available. English, Spanish.
Results Reference
derived

Learn more about this trial

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

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