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
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.
Drug: Hydroxychloroquine
Hydroxychloroquine pharmaceutical form will be tablets of 400 mg.
Drug: Placebo
Hydroxychloroquine placebo
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.
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