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

Phase 3

Completed

• Conditions: Coronavirus Infections; Pneumonia, Viral
• Interventions: Drug: Hydroxychloroquine; Drug: Hydroxychloroquine + azithromycin

• Registration Number: NCT04321278
• Lead Sponsor: 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.

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 Timeline

• Status Verified: 2020-03
• Study First Submitted: 2020-03-23
• Study First Submitted QC: 2020-03-23
• Study First Posted: 2020-03-25
• Study Start: 2020-03-28
• Primary Completion: 2020-06-14
• Study Completion: 2020-06-14
• Last Update Submitted: 2021-01-15
• Last Update Posted: 2021-01-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 440

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Time from treatment start to death	29 days after randomization	Time from treatment start to death
Number of days free from mechanical ventilation	29 days after randomization	Number of days free from mechanical ventilation at 29 days after randomization
Assess whether the tested therapies may be affected by leucocyte phenotype	Baseline	Leucocyte transcriptome
All-cause mortality	29 days after randomization	All-cause mortality rates at 29 days after randomization
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)
Duration of mechanical ventilation	29 days after randomization	Number of days that the patient was on mechanical ventilation after randomization
Duration of hospitalization	29 days after randomization	Length of hospital stay on survivors
Other secondary infections	29 days after randomization	Presence of other secondary infections
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

Trial Locations

Locations (57)

Hospital Moinhos de Vento; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Hospital de Urgência e Emergência de Rio Branco; 🇧🇷 Rio Branco, AC, Brazil

Hospital e Clínica São Roque; 🇧🇷 Ipiaú, BA, Brazil

Hospital da Cidade; 🇧🇷 Salvador, BA, Brazil

Hospital Maternidade São Vicente de Paulo; 🇧🇷 Barbalha, CE, Brazil

Hospital de Messejana Dr. Carlos Alberto Studart Gomes; 🇧🇷 Fortaleza, CE, Brazil

Hospital Unimed Cariri; 🇧🇷 Juazeiro Do Norte, CE, Brazil

Hospital Brasilia; 🇧🇷 Brasilia, DF, Brazil

Hospital Estadual Jayme dos Santos Neves; 🇧🇷 Serra, ES, Brazil

Hospital Evangélico de Vila Velha; 🇧🇷 Vila Velha, ES, Brazil

Secretaria de Estado de Saúde de Goias; 🇧🇷 Goiânia, GO, Brazil

Santa Casa de Misericórdia de Belo Horizonte Santa Casa de BH; 🇧🇷 Belo Horizonte, MG, Brazil

Hospital Santa Paula; 🇧🇷 São Paulo, SP, Brazil

Santa Casa da Misericordia - UTI (São João Del Rey); 🇧🇷 São João Del Rei, MG, Brazil

Hospital Maternidade E Pronto Socorro Santa Lucia Ltda; 🇧🇷 Poços De Caldas, Minas Gerais, Brazil

Hospital Adventista de Belem; 🇧🇷 Belem, PA, Brazil

Procape - Pronto S.Cardiologico de Pe.Prof.Luiz Tavares-; 🇧🇷 Recife, PE, Brazil

Hospital Giselda Trigueiro; 🇧🇷 Natal, Rio Grande Do Norte, Brazil

Irmandade da Santa Casa de Misericordia de Porto Alegre; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Hospital Naval Marcílio Dias; 🇧🇷 Rio de Janeiro, RJ, Brazil

Hospital São Lucas; 🇧🇷 Rio De Janeiro, RJ, Brazil

Associação Dr. Bartholomeu Tacchini; 🇧🇷 Bento Gonçalves, RS, Brazil

Hospital Geral de Caxias do Sul; 🇧🇷 Caxias Do Sul, RS, Brazil

Hospital Bruno Born; 🇧🇷 Lajeado, RS, Brazil

Hospital Nereu Ramos; 🇧🇷 Florianópolis, SC, Brazil

Hospital Universitário Polydoro Ernani de São Thiago/HU - UFSC; 🇧🇷 Florianópolis, SC, Brazil

Hospital Dona Helena; 🇧🇷 Joinville, SC, Brazil

Hospital Municipal Sao Jose; 🇧🇷 Joinville, SC, Brazil

AC Camargo Cancer Center - Fundação Antonio Prudente; 🇧🇷 São Paulo, SP, Brazil

Fundação do ABC (Hospital Estadual Mário Covas); 🇧🇷 Santo André, SP, Brazil

nstituto de Pesquisa Clínica de Campinas; 🇧🇷 Campinas, SP, Brazil

Hospital Moriah; 🇧🇷 São Paulo, SP, Brazil

Casa de Saude Santa Marcelina; 🇧🇷 São Paulo, SP, Brazil

Hospital São Camilo Pompeia; 🇧🇷 São Paulo, SP, Brazil

Hospital Israelita Albert Einstein; 🇧🇷 São Paulo, Brazil

Associacao Beneficente Siria; 🇧🇷 São Paulo, Brazil

Hospital Vila Santa Catarina; 🇧🇷 São Paulo, Brazil

Real e Benemérita Associação Portuguesa de Beneficência/SP - 1; 🇧🇷 São Paulo, Brazil

Secretaria de Saúde do Estado de São Paulo; 🇧🇷 São Paulo, Brazil

Serv Social da Industria do papel, papelão e cortiça do estado de SP; 🇧🇷 São Paulo, Brazil

Universidade Federal de São Paulo; 🇧🇷 São Paulo, Brazil

Sociedade Literaria e Caritativa Santo Agostinho; 🇧🇷 Criciúma, Santa Catarina, Brazil

Santa Casa de Misericordia de Votuporanga; 🇧🇷 Votuporanga, São Paulo, Brazil

Hospital Adventista de Belém; 🇧🇷 Belém, Pará, Brazil

Hospital Maternidade PROMATER; 🇧🇷 Natal, RN, Brazil

Liga Paranaense de Combate ao Câncer; 🇧🇷 Curitiba, PR, Brazil

Hospital São Vicente de Paulo; 🇧🇷 Passo Fundo, RS, Brazil

Centro Hospitalar Unimed; 🇧🇷 Joinville, SC, Brazil

Hospital Regional Hans Dieter Schmidt; 🇧🇷 Joinville, SC, Brazil

Hospital Alemão Oswaldo Cruz; 🇧🇷 São Paulo, SP, Brazil

Hospital Nove de Julho; 🇧🇷 São Paulo, SP, Brazil

A Beneficência Portuguesa de São Paulo - BP; 🇧🇷 São Paulo, Brazil

Sociedade Beneficente de Senhoras Hospital Sírio-Libanês; 🇧🇷 São Paulo, Brazil

Faculdade de Medicina de Botucatu; 🇧🇷 Botucatu, SP, Brazil

Universidade Estadual de Londrina; 🇧🇷 Londrina, Paraná, Brazil

Maestri E Kormann Consultoria Medico-Cientifica; 🇧🇷 Blumenau, Santa Catarina, Brazil

Fundação Pio XII; 🇧🇷 Barretos, São Paulo, Brazil