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

Pneumonia, Viral Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04321278
• Other study ID #: 30155020.5.1001.0071
• Status: Completed
• Phase: Phase 3
• Start date: March 28, 2020
• Est. completion date: June 14, 2020

Study information

• Verified date: March 2020
• Source: Hospital Israelita Albert Einstein
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 440
• Est. completion date: June 14, 2020
• Est. primary completion date: June 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronavirus Infections
• Infection
• Pneumonia
• Pneumonia, Viral
• Severe Acute Respiratory Syndrome

Intervention

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.
• 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.

Locations

Country	Name	City	State
Brazil	Hospital Maternidade São Vicente de Paulo	Barbalha	CE
Brazil	Fundação Pio XII	Barretos	São Paulo
Brazil	Hospital Adventista de Belem	Belem	PA
Brazil	Hospital Adventista de Belém	Belém	Pará
Brazil	Santa Casa de Misericórdia de Belo Horizonte Santa Casa de BH	Belo Horizonte	MG
Brazil	Associação Dr. Bartholomeu Tacchini	Bento Gonçalves	RS
Brazil	Maestri E Kormann Consultoria Medico-Cientifica	Blumenau	Santa Catarina
Brazil	Faculdade de Medicina de Botucatu	Botucatu	SP
Brazil	Hospital Brasilia	Brasilia	DF
Brazil	nstituto de Pesquisa Clínica de Campinas	Campinas	SP
Brazil	Hospital Geral de Caxias do Sul	Caxias Do Sul	RS
Brazil	Sociedade Literaria e Caritativa Santo Agostinho	Criciúma	Santa Catarina
Brazil	Liga Paranaense de Combate ao Câncer	Curitiba	PR
Brazil	Hospital Nereu Ramos	Florianópolis	SC
Brazil	Hospital Universitário Polydoro Ernani de São Thiago/HU - UFSC	Florianópolis	SC
Brazil	Hospital de Messejana Dr. Carlos Alberto Studart Gomes	Fortaleza	CE
Brazil	Secretaria de Estado de Saúde de Goias	Goiânia	GO
Brazil	Hospital e Clínica São Roque	Ipiaú	BA
Brazil	Centro Hospitalar Unimed	Joinville	SC
Brazil	Hospital Dona Helena	Joinville	SC
Brazil	Hospital Municipal Sao Jose	Joinville	SC
Brazil	Hospital Regional Hans Dieter Schmidt	Joinville	SC
Brazil	Hospital Unimed Cariri	Juazeiro Do Norte	CE
Brazil	Hospital Bruno Born	Lajeado	RS
Brazil	Universidade Estadual de Londrina	Londrina	Paraná
Brazil	Hospital Giselda Trigueiro	Natal	Rio Grande Do Norte
Brazil	Hospital Maternidade PROMATER	Natal	RN
Brazil	Hospital São Vicente de Paulo	Passo Fundo	RS
Brazil	Hospital Santa Paula	Passos	MG
Brazil	Hospital Maternidade E Pronto Socorro Santa Lucia Ltda	Poços De Caldas	Minas Gerais
Brazil	Hospital Moinhos de Vento	Porto Alegre	Rio Grande Do Sul
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Procape - Pronto S.Cardiologico de Pe.Prof.Luiz Tavares-	Recife	PE
Brazil	Hospital de Urgência e Emergência de Rio Branco	Rio Branco	AC
Brazil	Hospital Naval Marcílio Dias	Rio de Janeiro	RJ
Brazil	Hospital São Lucas	Rio De Janeiro	RJ
Brazil	Hospital da Cidade	Salvador	BA
Brazil	Fundação do ABC (Hospital Estadual Mário Covas)	Santo André	SP
Brazil	Santa Casa da Misericordia - UTI (São João Del Rey)	São João Del Rei	MG
Brazil	A Beneficência Portuguesa de São Paulo - BP	São Paulo
Brazil	AC Camargo Cancer Center - Fundação Antonio Prudente	São Paulo	SP
Brazil	Associacao Beneficente Siria	São Paulo
Brazil	Casa de Saude Santa Marcelina	São Paulo	SP
Brazil	Hospital Alemão Oswaldo Cruz	São Paulo	SP
Brazil	Hospital Israelita Albert Einstein	São Paulo
Brazil	Hospital Moriah	São Paulo	SP
Brazil	Hospital Nove de Julho	São Paulo	SP
Brazil	Hospital Santa Paula	São Paulo	SP
Brazil	Hospital São Camilo Pompeia	São Paulo	SP
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	Sociedade Beneficente de Senhoras Hospital Sírio-Libanês	São Paulo
Brazil	Universidade Federal de São Paulo	São Paulo
Brazil	Hospital Estadual Jayme dos Santos Neves	Serra	ES
Brazil	Hospital Evangélico de Vila Velha	Vila Velha	ES
Brazil	Santa Casa de Misericordia de Votuporanga	Votuporanga	São Paulo

Sponsors (5)

Lead Sponsor	Collaborator
Hospital Israelita Albert Einstein	Brazilian Research In Intensive Care Network, EMS, Hospital do Coracao, Hospital Sirio-Libanes

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	QT interval prolongation	Occurrence of QT interval prolongation	29 days after randomization
Other	Gastrointestinal intolerance	Occurrence of gastrointestinal intolerance	29 days after randomization
Other	Laboratory abnormalities	Occurrence of laboratory hematimetric parameters, creatinine and bilirubin	29 days after randomization
Other	Adverse events	Occurrence of adverse events related to the use of the investigational products	29 days after randomization
Primary	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)	15 days after randomization
Secondary	All-cause mortality	All-cause mortality rates at 29 days after randomization	29 days after randomization
Secondary	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)	7 and 29 days after randomization
Secondary	Number of days free from mechanical ventilation	Number of days free from mechanical ventilation at 29 days after randomization	29 days after randomization
Secondary	Duration of mechanical ventilation	Number of days that the patient was on mechanical ventilation after randomization	29 days after randomization
Secondary	Duration of hospitalization	Length of hospital stay on survivors	29 days after randomization
Secondary	Other secondary infections	Presence of other secondary infections	29 days after randomization
Secondary	Time from treatment start to death	Time from treatment start to death	29 days after randomization
Secondary	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	3, 6, 9 and 12 months
Secondary	Assess whether the tested therapies may be affected by leucocyte phenotype	Leucocyte transcriptome	Baseline