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

COVID-19 Clinical Trial

— COALITION-V  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04466540
• Other study ID #: 30415320.8.1001.0070
• Status: Completed
• Phase: Phase 4
• Start date: May 12, 2020
• Est. completion date: September 28, 2021

Study information

• Verified date: March 2022
• Source: Hospital Alemão Oswaldo Cruz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1372
• Est. completion date: September 28, 2021
• Est. primary completion date: July 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

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

Locations

Country	Name	City	State
Brazil	Santa Casa de Araras	Araras	São Paulo
Brazil	Hospital Maternidade São Vicente de Paulo	Barbalha	Ceará
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	Hospital Júlia Kubitschek	Belo Horizonte	Minas Gerais
Brazil	Instituto da Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa	Belo Horizonte	Minas Gerais
Brazil	Associação Dr. Bartholomeu Tacchini	Bento Gonçalves	Rio Grande Do Sul
Brazil	Maestri e Kormann Consultoria Medico Cientifica	Blumenau	Santa Catarina
Brazil	Faculdade de Medicina de Botucatu, UNESP	Botucatu	São Paulo
Brazil	Imigrantes Hospital e Maternidade	Brusque	Santa Catarina
Brazil	Unimed Sul Capixaba	Cachoeiro De Itapemirim	Espírito Santo
Brazil	Hospital do Rocio	Campo Largo	Paraná
Brazil	Hospital Regional do Litoral Norte	Caraguatatuba	São Paulo
Brazil	Casa de Caridade de Carangola	Carangola	Minas Gerais
Brazil	Hospital de Cordeirópolis	Cordeirópolis	São Paulo
Brazil	Hospital São José	Criciúma	Santa Catarina
Brazil	Hospital das Clínicas Universidade Federal de Goiás	Goiânia	Goiás
Brazil	Hospital e Clínica São Roque	Ipiaú	Bahia
Brazil	Centro de Combate ao Coronavírus de Itapevi	Itapevi	São Paulo
Brazil	Hospital Regional Hans Dieter Schmidt	Joinville	Santa Catarina
Brazil	Hospital Unimed Cariri	Juazeiro Do Norte	Ceará
Brazil	Dux Medicina	Jundiaí	São Paulo
Brazil	ESF Dr. João Paccola Primo	Lençois Paulista
Brazil	Centro de Pesquisas Clínicas Dr. Marco Mota HCOR	Maceió	Alagoas
Brazil	Clínica Clinilive	Maringá	Paraná
Brazil	Hospital Universitário Regional de Maringá	Maringá	Paraná
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	Irmandade de Misericórdia Do Hospital Da Santa Casa de Monte Alto	Monte alto	Salto Alto
Brazil	Complexo Hospitalar de Niterói	Niterói	Rio De Janeiro
Brazil	Hospital São Vicente de Paulo	Passo Fundo	Rio Grande Do Sul
Brazil	Santa Casa de Misericórdia de Passos	Passos	Minas Agerais
Brazil	Hospital Maternidade e Pronto Socorro Santa Lucia	Poços De Caldas	Minas Gerais
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	CEPEM Centro de Pesquisa de Medicina Tropical de Rondônia	Porto Velho	Rondônia
Brazil	PROCAPE	Recife	Pernambuco
Brazil	Real Hospital Português de Beneficência em Pernambuco	Recife	Pernambuco
Brazil	Faculdade de Medicina de Ribeirão Preto	Ribeirão Preto	São Paulo
Brazil	Unimed Ribeirão Preto	Ribeirão Preto	São Paulo
Brazil	Cardioclinica da Ilha do Governador	Rio De Janeiro
Brazil	SECRETARIA MUNICIPAL DE SAÚDE DE SAIRÉ (Unidade Mista Olília Mendonça Souto Maior)	Sairé	Pernambuco
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	Universidade Federal de Santa Maria	Santa Maria	Rio Grande Do Sul
Brazil	Hospital Casa de Saúde de Santos	Santos	São Paulo
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	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	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	International Research Center - Hospital Alemão Oswaldo Cruz	São Paulo
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 SAMUR	Vitória Da Conquista	Bahia
Brazil	Hospital Unimed Volta Redonda	Volta Redonda	Rio De Janeiro
Brazil	Santa Casa de Misericórdia de Votuporanga	Votuporanga	São Paulo

Sponsors (7)

Lead Sponsor	Collaborator
Hospital Alemão Oswaldo Cruz	Brazilian Research In Intensive Care Network, EMS S/A, Hospital do Coracao, Hospital Israelita Albert Einstein, Hospital Moinhos de Vento, Hospital Sirio-Libanes

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hypoglycemia	Change in the frequency of hypoglycemic episodes in diabetic patients using hypoglycemic medication, perceived by clinical signs or symptoms or measured in a capillary or blood glucose device	within 30 days from randomization
Other	Palpitations	Presence of cardiac arrhythmias in patients without known history of prolongation of the measure between Q wave and T wave in the heart's electrical cycle (QTc) or pre-existing heart disease;	within 30 days from randomization
Other	Reduced visual acuity	Change in visual acuity or new diagnosis of retinal disease not previously documented	within 30 days from randomization
Other	Diarrhea	Change in bowel habit greater than three (3) diarrheal episodes per day during the use of hydroxychloroquine medication and 3 days after its end	within 30 days from randomization
Other	Anorexia	Change in appetite during medication use hydroxychloroquine and 3 days after the end of treatment	within 30 days from randomization
Other	Emotional lability	Perception of change in emotional lability (mood swings) during hydroxychloroquine use and 3 days after the end of treatment	within 30 days from randomization
Other	Time to hospitalization after randomization	Time from randomization to hospitalization	within 30 days from randomization
Other	Assessment of the patient clinical status at the time of hospitalization	Clinical and vital signs assessed when admitted to hospital	within 30 days from randomization
Primary	Hospitalization	To assess if the treatment 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.	30 days from randomization
Secondary	Uncontrolled asthma after = 5 days of starting study medication	Affirmative answer in three or four items of the Global Initiative for Asthma (GINA) questionnaire	within 30 days from randomization
Secondary	Pneumonia	Defined by clinical-radiological criteria - a history of cough and one or more of the following symptoms: sputum, dyspnea, chest pain, sweating or fever (T> 37.8o C) + Chest CT scan showing ground-glass opacity, focal consolidations or mixed opacities (including reverse halo sign), uni or bilateral	within 30 days from randomization
Secondary	Otitis media	Defined by clinical criteria - Fever (T> 37.8o C) and otalgia + bulging of the tympanic membrane	within 30 days from randomization
Secondary	Fever resolution time	Day 0 of fever resolution will be defined as the first afebrile day (T <37.5o C) after inclusion in the study followed by at least two consecutive days. The temperature will be obtained through the participant report in the patient's diary	within 30 days from randomization
Secondary	Time to improve respiratory symptoms	Time to improve respiratory symptoms (cough, runny nose)	within 30 days from randomization
Secondary	Hospitalization in the Intensive Care Unit	Admission to ICU due to clinical reasons related to COVID-19	within 30 days from randomization
Secondary	Need for Orotracheal Intubation	Clinical need for Orotracheal Intubation as assessed by the physician responsible for the case	within 30 days from randomization
Secondary	Mechanical Ventilation Time	Number of days on mechanical ventilation until extubation or death	within 30 days from randomization
Secondary	Mortality	Death due to any cause that occurred within 30 days after inclusion in the study	within 30 days from randomization