Official Title
Pragmatic, Double-blind, Placebo-controlled Randomized Clinical Trial, Evaluating Hydroxychloroquine for Prevention of Hospitalization and Respiratory Complications in Non-hospitalized Patients With Confirmed or Probable COVID-19
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.

Completed
COVID-19

Drug: Hydroxychloroquine

Hydroxychloroquine pharmaceutical form will be tablets of 400 mg.

Drug: Placebo

Hydroxychloroquine placebo

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.

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Countries
Brazil
Locations

Centro de Pesquisas Clínicas Dr. Marco Mota HCOR
Maceió, Alagoas, Brazil

Hospital e Clínica São Roque
Ipiaú, Bahia, Brazil

Clínica Otorhinus
Salvador, Bahia, Brazil

Hospital da Bahia
Salvador, Bahia, Brazil

Hospital Santa Izabel
Salvador, Bahia, Brazil

Instituto Cárdio Pulmonar da Bahia
Salvador, Bahia, Brazil

Hospital SAMUR
Vitória Da Conquista, Bahia, 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 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

Álvaro Avezum, Ph.D, Principal Investigator
International Research Center - Hospital Alemão Oswaldo Cruz

Hospital Alemão Oswaldo Cruz
NCT Number
Keywords
Covid-19
Severe Acute Respiratory Syndrome - Coronavirus-2
hydroxychloroquine
COALITION Brazil V 2019
outpatients
MeSH Terms
COVID-19
Hydroxychloroquine