Safety and Efficacy of Hydroxychloroquine Associated With Azithromycin in SARS-Cov-2 Virus (COVID-19)

Coronavirus Infections Clinical Trial

— Coalition-I  

Official title:

An Open-label, Randomized Controlled Trial of Hydroxychloroquine and Azithromycin for COVID-19 Infection on Hospitalized, Noncritical Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04322123
• Other study ID #: Brazil COVID Coalition I Trial
• Status: Completed
• Phase: Phase 3
• Start date: April 1, 2020
• Est. completion date: June 2, 2020

Study information

• Verified date: April 2022
• Source: Hospital do Coracao
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Coronavirus (COVID-19) is a somewhat new and recognized infectious disease that is now spreading to several countries in the world, including Brazil. Hydroxychloroquine and azithromycin may be useful for treating those patients.

COALITION I study aims to compared standard of care, hydroxychloroquine plus azithromycin and hydroxychloroquine monotherapy for treatment of hospitalized patients with COVID-19.

COALITION I will recruit 630 patients with infection by COVID-19 (210 per arm). Ordinal endpoint of status at 15 days will be the primary endpoint.

Description:

The current pandemic associated with coronavirus disease 2019 (COVID-19) represents a major global health challenge. There are no effective therapies for the management of COVID-19 that have been proven to improve clinical outcomes in this high-risk group of patients. Hydroxychloroquine and its combination with azithromycin have been suggested to improve viral clearance, but its effect on clinical outcomes remains uncertain.

This is an open-label pragmatic multicentre randomized (concealed) clinical trial of 7 days of hydroxychloroquine (400 mg BID) plus azithromycin (500 mg once daily), hydroxychloroquine 400 mg BID, or standard of care for moderately severe hospitalized patients with suspected or confirmed COVID-19 (in-patients with up to 4L/minute oxygen supply through nasal catheter). Patients are randomized in around 50 recruiting sites (630 patients with confirmed COVID-19; 1:1:1; 210 patients per arm).

The primary endpoint is a 7-level ordinal scale measured at 15-days: 1) not hospitalized, without limitations on activities; 2) not hospitalized, with limitations on activities; 3) hospitalized, not using supplementary oxygen; 4) hospitalized, using supplementary oxygen; 5) hospitalized, using high-flow nasal cannula or non-invasive ventilation; 6) hospitalized, on mechanical ventilation; 7) death. Secondary endpoints are the ordinal scale at 7 days, need for mechanical ventilation and rescue therapies during 15 days, need of high-flow nasal cannula or non-invasive ventilation during 15 days, length of hospital stay, in-hospital mortality, thromboembolic events, occurrence of acute kidney injury, defined as an increase in creatinine above 1.5 times the baseline value and number of days free of respiratory support at 15 days. Secondary safety outcomes include prolongation of QT interval on electrocardiogram, ventricular arrhythmias, and liver toxicity. The main analysis will consider all patients with confirmed COVID-19 in the groups they were randomly assigned.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 667
• Est. completion date: June 2, 2020
• Est. primary completion date: June 2, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with suspected or confirmed COVID-19 admitted to inpatient units and intensive care units

Exclusion Criteria:

• Need for oxygen supplementation > 4 litters per min

• Patients using a high-flow nasal catheter

• Patients using non-invasive mechanical ventilation

• Patients using invasive mechanical ventilation

• Males and females aged < 18 years

• Pregnancy

• Allergy to chloroquine or derivatives

• Allergy to azithromycin

• Patients that have already received more than one dose of either azithromycin or hydroxychloroquine before enrollment

• Patients with respiratory symptoms for more than 14 days

Related Conditions & MeSH terms

• Coronavirus Infections
• Infections

Intervention

Drug:
• Hydroxychloroquine Oral Product
Hydroxychloroquine 400 mg BID
• Hydroxychloroquine + azithromycin
Hydroxychloroquine 400 mg BID + azithromycin 500 mg once a day

Locations

Country	Name	City	State
Brazil	Hospital de Amor - Unidade Barretos (Fundação PIO XII)	Barretos	SP
Brazil	Hospital de Brasília	Brasilia	DF
Brazil	Instituto de Cardiologia do Distrito Federal	Brasília	DF
Brazil	Hospital Geral de Caxias do Sul	Caxias do Sul	RS
Brazil	Hospital Maternidade São José - UNESC - Fundação Social Rural de Colatina	Colatina	ES
Brazil	Hospital São José	Criciuma	SC
Brazil	Hospital Geral Clériston Andrade	Feira De Santana	BA
Brazil	Hospital Baía Sul - Baía Sul Medical Center	Florianópolis	SC
Brazil	Hospital Nereu Ramos	Florianópolis	Sc
Brazil	Centro Hospitalar Unimed	Joinville	SC
Brazil	Associação Evangélica Beneficente de Londrina - Hospital Evangélico de Londrina	Londrina	PR
Brazil	Hospital Vila da Serra	Nova Lima	MG
Brazil	Hospital Santa Rita - Irmandade Santa Casa de Porto Alegre	Porto Alegre	RS
Brazil	Hospital São Francisco - Irmandade Santa Casa de Porto Alegre	Porto Alegre	RS
Brazil	Instituto Estadual do Cérebro Paulo Niemeyer	Rio De Janeiro	RJ
Brazil	Hospital Ana Nery - HAN/SESAB	Salvador	BA
Brazil	Santa Casa de Misericórdia de São João Del Rei	São João Del Rei	MG
Brazil	Casa de Saúde Santa Marcelina	São Paulo	SP
Brazil	Hospital Albert Einstein	São Paulo	SP
Brazil	Hospital Beneficência Portuguesa - Real e Benemérita Associação Portuguesa de Beneficência	São Paulo	SP
Brazil	Hospital BP Mirante - Real e Benemérita	São Paulo	SP
Brazil	Hospital das Clínicas da FMUSP	São Paulo	SP
Brazil	Hospital do Servidor Público Estadual - HSPE - IAMSPE	São Paulo	SP
Brazil	Hospital São Paulo - UNIFESP	São Paulo	SP
Brazil	Hospital SEPACO	São Paulo	S
Brazil	Hospital Sírio-Libanês	São Paulo	SP
Brazil	HHospital SAMUR	Vitória Da Conquista	BA
Brazil	Hospital Geral de Vitória da Conquista	Vitória Da Conquista	BA

Sponsors (5)

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

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety outcome on corrected QT interval	Corrected QT interval	At day 3 and 7 after enrollment
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 7 points.; Alive at home without limitations on activities; Alive at home without limitations on activities; In the hospital without oxygen; In the hospital using oxygen; In the hospital using high-flow nasal catheter or non-invasive ventilation; In hospital, on mechanical ventilation; Dead	15 days after randomization
Secondary	Ordinal scale in 7 days	Evaluation of the clinical status of patients on the 7th day after randomization defined by the Ordinal Scale of 7 points.; Alive at home without limitations on activities; Alive at home without limitations on activities; In the hospital without oxygen; In the hospital using oxygen; In the hospital using high-flow nasal catheter or non-invasive ventilation; In hospital, on mechanical ventilation; Dead	7 days after randomization
Secondary	Need of intubation and mechanical ventilation	Need of intubation and mechanical ventilation up to the 7th day after randomization	7 days after randomization
Secondary	Use of mechanical ventilation during hospital stay	Use of mechanical ventilation during hospital stay	15 days after randomization
Secondary	Use of non-invasive ventilation	Use of non-invasive ventilation up to the 7th day after randomization	7 days after randomization
Secondary	Hospital Length of Stay	Hospital Length of Stay	28 days after randomization
Secondary	All-cause mortality	All-cause mortality rates during hospital stay	28 days after randomization
Secondary	Thromboembolic complications	Occurrence of thromboembolic complications such as: Deep vein thrombosis Pulmonary Embolism Stroke	15 days after randomization
Secondary	Acute renal disfunction	Occurrence of renal dysfunction, defined as an increase in creatinine above 1.5 times the baseline value	15 days after randomization
Secondary	Number of days alive and free of respiratory support up to 15 days	Number of days alive and free of respiratory support up to 15 days (DAFOR15), defined as the sum of days patients did not require supplementary oxygen, non-invasive ventilation, high-flow nasal catheter neither mechanical ventilation at 15 -days. Patients that perished during the 15-day window will receive zero DAFOR15.	15 days