Randomized Placebo-controlled Trial of Hydroxychloroquine in Outpatient Cases With Coronavirus Disease 2019 (COVID-19)

NCT ID: NCT04466540

Last Updated: 2022-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1372 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-12
• Study Completion Date: 2021-09-28

Brief Summary

In December 2019, a group of patients with pneumonia of unknown cause was identified in Wuhan, in the Hubei province, China. Despite the need of target specific therapeutic options for COVID-19, until now there is no proof of effectiveness of any specific intervention. Some limited observational trials and also evidence from randomized trials have shown no benefit of hydroxychloroquine in inpatient context. Thus, studies evaluating interventions in an outpatient setting in non-severe patients can provide important information related to prognosis and safety. In this way, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine in COVID-19 outpatients by means of a Randomized, double-blind, placebo-controlled trial

Detailed Description

Pragmatic, double-blind, placebo-controlled randomized parallel-group, two-arm clinical trial (with allocation ratio 1:1), evaluating hydroxychloroquine (800 mg at 1st day, and 400 mg from day 2 to 7) for prevention of hospitalization and respiratory complications in non-hospitalized confirmed or suspected COVID-19 cases. Key inclusion criteria are adults (equal to or greater tahn 18 years) seeking medical care with suspected or confirmed COVID-19, with time between symptoms and inclusion ≤ 07 days, presenting mild symptoms, without indication of hospitalization and at least one risk factor for complication (> 65 years; hypertension; diabetes mellitus; asthma; Chronic Obstructive Pulmonary Disease (COPD) or other chronic lung diseases; smoking; immunosuppression; obesity (Defined as BMI equal to or greater than 30 Kg/m2). Primary endpoint is to assess if the treatment with hydroxychloroquine is able to avoid hospitalization due to a COVID-19-related clinical reason within 30 days of randomization in an outpatient setting. Hospitalization is considered to be hospital stay for a period > 24h or an additional hospitalized calendar day. The primary endpoint is centrally adjudicated by an independent clinical events committee blinded to the assigned treatment groups. Secondary endpoints include uncontrolled asthma after ≥ 5 days of starting study medication; pneumonia; otitis media; fever resolution time; time to improve respiratory symptoms; hospitalization in the Intensive Care Unit; need for orotracheal intubation; mechanical ventilation time; mortality. Safety outcomes will be hypoglycemia; palpitations; reduced visual acuity; diarrhea; anorexia; and emotional lability. The evaluation of the primary outcome (hospitalization within 30 days) will be performed for the included population following the principle of intention-to-treat (ITT), which will consist of all randomized cases. A modified intention-to-treat analysis (mITT), in which cases definitely confirmed as negative for COVID-19 will be excluded, will also be performed.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Hydroxychloroquine (HCQ)

HCQ group participants will receive a dose of 400mg twice daily (BID) in the first day, and a dose of 400 mg once daily (OD) from the second day of treatment, in a total of 7 days.

Group Type: EXPERIMENTAL

Hydroxychloroquine

Intervention Type: DRUG

Hydroxychloroquine pharmaceutical form will be tablets of 400 mg.

Placebo

The placebo group will follow the same regimen of administration

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Hydroxychloroquine placebo

Interventions

Hydroxychloroquine

Hydroxychloroquine pharmaceutical form will be tablets of 400 mg.

Intervention Type: DRUG

Placebo

Hydroxychloroquine placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

It will be considered eligible those adults (equal to or greater than 18 years) seeking medical care with suspected or confirmed COVID-19, with time between symptoms and inclusion ≤ 07 days, presenting mild symptoms, without indication of hospitalization and at least 1 risk factor for complication:

1. > 65 years;

2. Hypertension;

3. Diabetes mellitus;

4. Asthma;

5. COPD or other chronic lung diseases;

6. Smoking;

7. Immunosuppression;

8. Obesity (Defined as BMI equal to or greater than 30 Kg/m2).

Exclusion Criteria

1. Patients under 18 years old;

2. Hospitalization at the first medical care;

3. Positive test for influenza at the first medical care;

4. Known hypersensitivity to hydroxychloroquine / chloroquine;

5. Previous diagnosis of retinopathy or macular degeneration;

6. Previous diagnosis of Long QT-syndrome, history of sudden death in close family members (parents and siblings), decompensated heart failure, unstable coronary artery disease, use of anti-arrhythmic drugs or other drugs that can increase the hydroxychloroquine bioavailability or enhance its effect;

7. Evidence of known liver disease, reported by the patient;

8. Evidence of known chronic kidney disease, reported by the patient;

9. Patients with pancreatitis;

10. Baseline ECG with QTc interval ≥ 480ms;

11. Chronic use of hydroxychloroquine/chloroquine for other reasons;

12. Pregnancy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EMS S/A

UNKNOWN

Sponsor Role: collaborator

Hospital do Coracao

OTHER

Sponsor Role: collaborator

Hospital Israelita Albert Einstein

OTHER

Sponsor Role: collaborator

Hospital Sirio-Libanes

OTHER

Sponsor Role: collaborator

Hospital Moinhos de Vento

OTHER

Sponsor Role: collaborator

Brazilian Research In Intensive Care Network

NETWORK

Sponsor Role: collaborator

Hospital Alemão Oswaldo Cruz

OTHER

Sponsor Role: lead

Responsible Party

Álvaro Avezum Junior

Research Manager - International Research Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Álvaro Avezum, Ph.D

Role: PRINCIPAL_INVESTIGATOR

International Research Center - Hospital Alemão Oswaldo Cruz

Locations

Centro de Pesquisas Clínicas Dr. Marco Mota HCOR

Maceió, Alagoas, Brazil

Hospital Maternidade São Vicente de Paulo

Barbalha, Ceará, Brazil

Hospital Unimed Cariri

Juazeiro do Norte, Ceará, Brazil

Unimed Sul Capixaba

Cachoeiro de Itapemirim, Espírito Santo, Brazil

Hospital e Clínica São Roque

Ipiaú, Estado de Bahia, Brazil

Clínica Otorhinus

Salvador, Estado de Bahia, Brazil

Hospital da Bahia

Salvador, Estado de Bahia, Brazil

Hospital Santa Izabel

Salvador, Estado de Bahia, Brazil

Instituto Cárdio Pulmonar da Bahia

Salvador, Estado de Bahia, Brazil

Hospital SAMUR

Vitória da Conquista, Estado de Bahia, Brazil

Hospital das Clínicas Universidade Federal de Goiás

Goiânia, Goiás, Brazil

Santa Casa de Misericórdia de Passos

Passos, Minas Agerais, Brazil

Hospital Júlia Kubitschek

Belo Horizonte, Minas Gerais, Brazil

Instituto da Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa

Belo Horizonte, Minas Gerais, Brazil

Casa de Caridade de Carangola

Carangola, Minas Gerais, Brazil

Hospital Maternidade e Pronto Socorro Santa Lucia

Poços de Caldas, Minas Gerais, Brazil

Hospital da Unimed

São João del Rei, Minas Gerais, Brazil

Santa Casa de Misericórdia de São João Del Rei

São João del Rei, Minas Gerais, Brazil

Hospital de Clínicas da Universidade Federal do Triangulo Mineiro

Uberaba, Minas Gerais, Brazil

Hospital de Clínicas da Universidade Federal de Uberlândia

Uberlândia, Minas Gerais, Brazil

Hospital do Rocio

Campo Largo, Paraná, Brazil

Clínica Clinilive

Maringá, Paraná, Brazil

Hospital Universitário Regional de Maringá

Maringá, Paraná, Brazil

PROCAPE

Recife, Pernambuco, Brazil

Real Hospital Português de Beneficência em Pernambuco

Recife, Pernambuco, Brazil

SECRETARIA MUNICIPAL DE SAÚDE DE SAIRÉ (Unidade Mista Olília Mendonça Souto Maior)

Sairé, Pernambuco, Brazil

Complexo Hospitalar de Niterói

Niterói, Rio de Janeiro, Brazil

Hospital Unimed Volta Redonda

Volta Redonda, Rio de Janeiro, Brazil

Associação Dr. Bartholomeu Tacchini

Bento Gonçalves, Rio Grande do Sul, Brazil

Hospital São Vicente de Paulo

Passo Fundo, Rio Grande do Sul, Brazil

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, Brazil

Santa Casa de Misericórdia de Porto Alegre (ISCMPA)

Porto Alegre, Rio Grande do Sul, Brazil

Universidade Federal de Santa Maria

Santa Maria, Rio Grande do Sul, Brazil

CEPEM Centro de Pesquisa de Medicina Tropical de Rondônia

Porto Velho, Rondônia, Brazil

Irmandade de Misericórdia Do Hospital Da Santa Casa de Monte Alto

Monte Alto, Salto Alto, Brazil

Maestri e Kormann Consultoria Medico Cientifica

Blumenau, Santa Catarina, Brazil

Imigrantes Hospital e Maternidade

Brusque, Santa Catarina, Brazil

Hospital São José

Criciúma, Santa Catarina, Brazil

Hospital Regional Hans Dieter Schmidt

Joinville, Santa Catarina, Brazil

Santa Casa de Araras

Araras, São Paulo, Brazil

Hospital de Amor

Barretos, São Paulo, Brazil

Santa Casa de Misericórdia de Barretos

Barretos, São Paulo, Brazil

Alphacor Cardiologia Clinica E Diagnóstica LTDA

Barueri, São Paulo, Brazil

Faculdade de Medicina de Botucatu, UNESP

Botucatu, São Paulo, Brazil

Hospital Regional do Litoral Norte

Caraguatatuba, São Paulo, Brazil

Hospital de Cordeirópolis

Cordeirópolis, São Paulo, Brazil

Centro de Combate ao Coronavírus de Itapevi

Itapevi, São Paulo, Brazil

Dux Medicina

Jundiaí, São Paulo, Brazil

Hospital Carlos Fenando Malzoni

Matão, São Paulo, Brazil

Centro de Atendimento Para O Enfrentamento A Covid-19 Da Prefeitura Municipal de Monte Altoprefeitura de Monte Alto

Monte Alto, São Paulo, Brazil

Faculdade de Medicina de Ribeirão Preto

Ribeirão Preto, São Paulo, Brazil

Unimed Ribeirão Preto

Ribeirão Preto, São Paulo, Brazil

Hospital Casa de Saúde de Santos

Santos, São Paulo, Brazil

Kaiser Clínica e Hospital Dia

São José do Rio Preto, São Paulo, Brazil

Hospital Policlin

São José dos Campos, São Paulo, Brazil

Hospital Regional de São José dos Campos

São José dos Campos, São Paulo, Brazil

Santa Casa de Misericórdia de Votuporanga

Votuporanga, São Paulo, Brazil

ESF Dr. João Paccola Primo

Lençois Paulista, , Brazil

Cardioclinica da Ilha do Governador

Rio de Janeiro, , Brazil

International Research Center - Hospital Alemão Oswaldo Cruz

São Paulo, , Brazil

Hospital do Coração

São Paulo, , Brazil

Hospital Israelita Albert Einstein

São Paulo, , Brazil

Hospital Leforte

São Paulo, , Brazil

Hospital Moriah

São Paulo, , Brazil

Hospital Samaritano

São Paulo, , Brazil

Hospital Santa Paula

São Paulo, , Brazil

Hospital São Camilo Pompéia

São Paulo, , Brazil

Hospital São Paulo - UNIFESP

São Paulo, , Brazil

Hospital Sírio-Libanês

São Paulo, , Brazil

Countries

Brazil

References

Avezum A, Oliveira GBF, Oliveira H, Lucchetta RC, Pereira VFA, Dabarian AL, D O Vieira R, Silva DV, Kormann APM, Tognon AP, De Gasperi R, Hernandes ME, Feitosa ADM, Piscopo A, Souza AS, Miguel CH, Nogueira VO, Minelli C, Magalhaes CC, Morejon KML, Bicudo LS, Souza GEC, Gomes MAM, Fo JJFR, Schwarzbold AV, Zilli A, Amazonas RB, Moreira FR, Alves LBO, Assis SRL, Neves PDMM, Matuoka JY, Boszczowski I, Catarino DGM, Veiga VC, Azevedo LCP, Rosa RG, Lopes RD, Cavalcanti AB, Berwanger O; COPE - COALITION COVID-19 Brazil V Investigators. Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE - Coalition V): A double-blind, multicentre, randomised, controlled trial. Lancet Reg Health Am. 2022 Jul;11:100243. doi: 10.1016/j.lana.2022.100243. Epub 2022 Mar 31.

Reference Type: DERIVED

PMID: 35378952 (View on PubMed)

Oliveira Junior HA, Ferri CP, Boszczowski I, Oliveira GBF, Cavalcanti AB, Rosa RG, Lopes RD, Azevedo LCP, Veiga VC, Berwanger O, Avezum A. Rationale and Design of the COVID-19 Outpatient Prevention Evaluation (COPE - Coalition V) Randomized Clinical Trial: Hydroxychloroquine vs. Placebo in Non-Hospitalized Patients. Arq Bras Cardiol. 2022 Feb;118(2):378-387. doi: 10.36660/abc.20210832. English, Portuguese.

Reference Type: DERIVED

PMID: 35262569 (View on PubMed)

Other Identifiers

30415320.8.1001.0070

Identifier Type: -

Identifier Source: org_study_id