Clincosm LogoSign in Get a demo

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

Sponsor
Hospital do Coracao (Other)
Overall Status
Completed
CT.gov ID
NCT04322123
Collaborator
Hospital Israelita Albert Einstein (Other), Hospital Sirio-Libanes (Other), Brazilian Research In Intensive Care Network (Other), EMS (Industry)
667
Enrollment
28
Locations
3
Arms
2
Actual Duration (Months)
23.8
Patients Per Site
11.7
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Hydroxychloroquine Oral Product
  • Drug: Hydroxychloroquine + azithromycin
 Phase 3

Detailed 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
667 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Randomized Controlled Trial of Hydroxychloroquine and Azithromycin for COVID-19 Infection on Hospitalized, Noncritical Patients
Actual Study Start Date :
Apr 1, 2020
Actual Primary Completion Date :
Jun 2, 2020
Actual Study Completion Date :
Jun 2, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Hydroxychloroquine

Hydroxychloroquine after randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] for 07 days.

Drug: Hydroxychloroquine Oral Product
Hydroxychloroquine 400 mg BID
Experimental: Hydroxychloroquine + azithromycin

Hydroxychloroquine + azithromycin. After randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] + azithromycin [500mg 1x/day]) for 07 days.

Drug: Hydroxychloroquine + azithromycin
Hydroxychloroquine 400 mg BID + azithromycin 500 mg once a day
No Intervention: Control

standard treatment protocol for 2019-nCoV infection.

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 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

Secondary Outcome Measures

  1. Ordinal scale in 7 days [7 days after randomization]

    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

  2. Need of intubation and mechanical ventilation [7 days after randomization]

    Need of intubation and mechanical ventilation up to the 7th day after randomization

  3. Use of mechanical ventilation during hospital stay [15 days after randomization]

    Use of mechanical ventilation during hospital stay

  4. Use of non-invasive ventilation [7 days after randomization]

    Use of non-invasive ventilation up to the 7th day after randomization

  5. Hospital Length of Stay [28 days after randomization]

    Hospital Length of Stay

  6. All-cause mortality [28 days after randomization]

    All-cause mortality rates during hospital stay

  7. Thromboembolic complications [15 days after randomization]

    Occurrence of thromboembolic complications such as: Deep vein thrombosis Pulmonary Embolism Stroke

  8. Acute renal disfunction [15 days after randomization]

    Occurrence of renal dysfunction, defined as an increase in creatinine above 1.5 times the baseline value

  9. Number of days alive and free of respiratory support up to 15 days [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.

Other Outcome Measures

  1. Safety outcome on corrected QT interval [At day 3 and 7 after enrollment]

    Corrected QT interval

Eligibility Criteria

Criteria

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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Hospital Geral Clériston Andrade Feira De Santana BA Brazil
2 Hospital Ana Nery - HAN/SESAB Salvador BA Brazil
3 HHospital SAMUR Vitória Da Conquista BA Brazil
4 Hospital Geral de Vitória da Conquista Vitória Da Conquista BA Brazil
5 Hospital de Brasília Brasilia DF Brazil
6 Instituto de Cardiologia do Distrito Federal Brasília DF Brazil
7 Hospital Maternidade São José - UNESC - Fundação Social Rural de Colatina Colatina ES Brazil
8 Hospital Vila da Serra Nova Lima MG Brazil
9 Santa Casa de Misericórdia de São João Del Rei São João Del Rei MG Brazil
10 Associação Evangélica Beneficente de Londrina - Hospital Evangélico de Londrina Londrina PR Brazil
11 Instituto Estadual do Cérebro Paulo Niemeyer Rio De Janeiro RJ Brazil
12 Hospital Geral de Caxias do Sul Caxias do Sul RS Brazil
13 Hospital Santa Rita - Irmandade Santa Casa de Porto Alegre Porto Alegre RS Brazil
14 Hospital São Francisco - Irmandade Santa Casa de Porto Alegre Porto Alegre RS Brazil
15 Hospital São José Criciuma SC Brazil
16 Hospital Baía Sul - Baía Sul Medical Center Florianópolis SC Brazil
17 Hospital Nereu Ramos Florianópolis Sc Brazil
18 Centro Hospitalar Unimed Joinville SC Brazil
19 Hospital de Amor - Unidade Barretos (Fundação PIO XII) Barretos SP Brazil
20 Casa de Saúde Santa Marcelina São Paulo SP Brazil
21 Hospital Albert Einstein São Paulo SP Brazil
22 Hospital Beneficência Portuguesa - Real e Benemérita Associação Portuguesa de Beneficência São Paulo SP Brazil
23 Hospital BP Mirante - Real e Benemérita São Paulo SP Brazil
24 Hospital das Clínicas da FMUSP São Paulo SP Brazil
25 Hospital do Servidor Público Estadual - HSPE - IAMSPE São Paulo SP Brazil
26 Hospital São Paulo - UNIFESP São Paulo SP Brazil
27 Hospital Sírio-Libanês São Paulo SP Brazil
28 Hospital SEPACO São Paulo S Brazil

Sponsors and Collaborators

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

Investigators

  • Study Chair: Alexandre Biasi, PhD, Hospital do Coração
  • Principal Investigator: Otavio Berwanger, Hospital Israelita Albert Einstein

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Hospital do Coracao
ClinicalTrials.gov Identifier:
NCT04322123
Other Study ID Numbers:
  • Brazil COVID Coalition I Trial
First Posted:
Mar 26, 2020
Last Update Posted:
Apr 5, 2022
Last Verified:
Apr 1, 2022
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
Additional relevant MeSH terms:
Infections
Coronavirus Infections
Azithromycin
Hydroxychloroquine

Study Results

No Results Posted as of Apr 5, 2022