Hydroxychloroquine and Lopinavir/ Ritonavir to Improve the Health of People With COVID-19: "The Hope Coalition - 1"

NCT04403100 | Unknown Phase 3 DMC

• 1 other identifier: COVID19_AMB_Brasil
• Study Type: interventional
• Target: 1,968
• Locations: 1 country
• Sites: 4

Brief Summary

The COVID-19 pandemic has been characterized by high morbidity and mortality, especially in certain subgroups of patients. To date, no treatment has been shown to be effective in controlling this disease in hospitalized patients with moderate and / or severe cases of this disease. Hydroxychloroquine and lopinavir / ritonavir have been shown to inhibit SARS-CoV viral replication in experimental severe acute respiratory symptoms models and have similar activity against SARS-CoV2. Although widely used in studies of critically ill patients, to date, no study has demonstrated its role on the treatment of high-risk, newly diagnosed patients with COVID-19 and mild symptoms.

Conditions

COVID-19; Coronavirus Infection; Virus Disease; Acute Respiratory Infection; SARS-CoV Infection

Outcome Measures

Primary Outcomes (2)

• Proportion of participants who were hospitalized for progression of COVID-19 disease

  Hospitalization is defined as at least 24 hours of acute care in a hospital or similar acute care facility (emergency settings, temporary emergency facilities created for acute care of COVID-19 pandemic)

  Measuring during 28-day period since randomization (Intention to treat analysis)

• Proportion of participants who died due to COVID-19 progression and/ or complications

  Measuring during 28-day period since randomization (Intention to treat analysis)

Secondary Outcomes (9)

• Proportion of participants with viral load change on 03, 07, 10 and 14 after randomization

  Measuring during 14-day period since randomization

• Time to clinical improvement

  Measuring during 28-day period since randomization

• Time to clinical failure

  Measuring during 28-day period since randomization

• Hospitalization for any cause

  Measuring during 28-day period since randomization

• Proportion of participants who died due to pulmonary complications

  Measuring during 28-day period since randomization

Study Arms (4)

Hydroxychloroquine Sulfate

ACTIVE COMPARATOR

Hydroxychloroquine 400 mg. Loading oral dose of 800 mg followed by orally dose of 400 mg/ day for the following 10 days

Drug: Hydroxychloroquine Sulfate Tablets

Lopinavir/ Ritonavir

ACTIVE COMPARATOR

Lopinavir Ritonavir 200/ 50 mg Loading oral dose of 800/ 200 mg twice a day on day 1 followed by 400/100 mg orally twice a day for the following 9 days

Drug: Lopinavir/ Ritonavir Oral Tablet

Hydroxychloroquine plus Lopinavir/ Ritonavir

ACTIVE COMPARATOR

Hydroxychloroquine 400 mg. Loading oral dose of 800 mg followed by orally dose of 400 mg/ day for the following 10 days Plus Lopinavir Ritonavir 200/ 50 mg Loading oral dose of 800/ 200 mg twice a day on day 1 followed by 400/100 mg orally twice a day for the following 9 days

Drug: Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets

Placebo

PLACEBO COMPARATOR

Placebo Twice a day from day 1 through day 10.

Drug: Placebo

Interventions

Hydroxychloroquine Sulfate Tablets DRUG

Tablets of 400 mg: Loading dose of 02 tablets followed by one tablet of 400 mg orally on the following 09 days

Hydroxychloroquine Sulfate

Lopinavir/ Ritonavir Oral Tablet DRUG

tablets of 200/ 50 mg; Loading dose of 04 tablets twice a day on day 1 followed by two tablets twice a day on the following 09 days

Lopinavir/ Ritonavir

Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets DRUG

Hydroxychloroquine Oral Tablet 400 mg: Loading dose of 02 tablets followed by one tablet of 400 mg orally on the following 09 days plus Lopinavir/ Ritonavir Oral Tablet of 200/ 50 mg: Loading dose of 04 tablets twice a day on day 1 followed by two tablets twice a day on the following 09 days

Hydroxychloroquine plus Lopinavir/ Ritonavir

Placebo DRUG

Placebo tablets - 01 tablet twice daily from day 01 through day 10.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with RT-PCR diagnosis of COVID-19 or a clinical condition compatible with COVID-19 and respiratory symptoms, presenting:
• A. Persistent dry cough associated with axillary temperature \> 37.7 Celsius;
• B. Recent onset of Flu-like Respiratory Symptoms associated with dry cough
• C. Tomographic image compatible with COVID 19 infection;
• \. Men and women aged \> 50 years OR: Patients over 18 years of age with at least one of the following criteria
• Diabetes requiring oral medication or insulin.
• Arterial hypertension requiring at least 01 oral medication for treatment
• Known cardiovascular diseases (CHF of any etiology, documented Coronary Artery Disease, Clinically overt heart disease)
• Symptomatic chronic lung disease and/ or medically controlled
• Patients with a history of transplantation
• Patient with stage IV chronic kidney disease or on dialysis.
• Patients on current Immunosuppression and/or using corticosteroid therapy (equivalent to at least 10 mg of oral prednisone per day)
• Willingness to comply with study related procedures
• \. Ability to provide informed consent before any protocol-related procedures.

You may not qualify if:

• RT-PCR exam for COVID-19 negative during the screening visit.
• Patients with an acute respiratory condition compatible with COVID-19 being hospitalized;
• Patients with an acute respiratory condition and with moderate to high probability of not being a COVID infection 19;
• Dyspnea secondary to other acute and chronic respiratory causes or infections (eg, decompensated Chronic Obstructive Pulmonary Disease, acute bronchitis, pneumonia, primary pulmonary arterial hypertension);
• Severe respiratory clinical condition, presenting at least ONE of the criteria below:
• Respiratory Rate\> 28 / min;
• Arterial Oxygen Saturation \< 92% with nasal oxygen therapy at 10 l/ min;
• PaO2 / FIO2 \<300 mmHg
• \. History of Cardiac Arrhythmia or Long QT Syndrome; 5. Use of Medications that are known to prolong QTc: Citalopram, Venlafaxine, Bupropion and with no possibility of suspension during the period of investigational medical product administration. 6. Inability to take oral medications; 7. Patients on continuous use of Amiodarone and / or PGE5 Inhibitors (Ex .: Sildenafil and similar). 8. Use of Digoxin, Cyclosporine, Cimetidine, Tamoxifen. 9. Use of anticonvulsants, antifungals, immunosuppressants other than corticotherapy. 10. Use of Hydroxychloroquine for other indications 11. Use of chemoprophylaxis for malaria. 12. Psoriasis in a form other than cutaneous 13. Porphyria 14. Use of protease inhibitors, ritonavir or Cobicistat 15. Clinical history of Liver Cirrhosis or Child-Pugh C classification; 16. Patients with a history of degenerative retinal diseases (patients with retinal diseases due to diabetes and hypertension can participate in the research); 17. Patient with a clinically relevant history of hearing loss; 18. Patients with known severe degenerative neurological diseases and / or severe mental illness; 19. Inability of the patient or representative to give consent or adhere to the procedures proposed in the protocol; 20. Known hypersensitivity and / or intolerance to Hydroxychloroquine. 21. Hypersensitivity and / or intolerance Lopinavir / Ritonavir

Sponsors & Collaborators

• Cardresearch: lead
• Cardresearch - Cardiologia Assistencial e de Pesquisa LTDA: collaborator
• Cytel Inc.: collaborator

Study Sites (4)

CARDRESEARCH - Cardiologia Assistencial e de Pesquisa

Belo Horizonte, Minas Gerais, 30150240, Brazil

RECRUITING

Pontificia Universidade Catolica de Minas Gerais

Belo Horizonte, Minas Gerais, 30535901, Brazil

NOT YET RECRUITING

Fundo Municipal de Saúde de Betim

Betim, Minas Gerais, 32600412, Brazil

RECRUITING

Universidade Federal de Ouro Preto

Ouro Preto, Minas Gerais, 35400000, Brazil

NOT YET RECRUITING

Related Publications (1)

• Reis G, Moreira Silva EADS, Medeiros Silva DC, Thabane L, Singh G, Park JJH, Forrest JI, Harari O, Quirino Dos Santos CV, Guimaraes de Almeida APF, Figueiredo Neto AD, Savassi LCM, Milagres AC, Teixeira MM, Simplicio MIC, Ribeiro LB, Oliveira R, Mills EJ; TOGETHER Investigators. Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19: The TOGETHER Randomized Clinical Trial. JAMA Netw Open. 2021 Apr 1;4(4):e216468. doi: 10.1001/jamanetworkopen.2021.6468.

  PMID: 33885775 DERIVED

MeSH Terms

Conditions

COVID-19; Coronavirus Infections; Virus Diseases; Severe Acute Respiratory Syndrome

Interventions

Hydroxychloroquine; Lopinavir; Ritonavir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles

Study Officials

• Gilmar Reis, MD, PhD

  Cardresearch - Cardiologia Assistencial e de Pesquisa LTDA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gilmar Reis, MD, PhD

CONTACT

+5531332416574; greisbh@uol.com.br

Rosemary Oliveira, SC

CONTACT

+5531992636703; roliveira@cardresearch.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The investigational medical product will be packaged in similar bottles by a third party who will keep the allocation confidential until the end of the study. The bottles will be sealed and identified as "Research Product A, B and C" and with different colored labels. They will be randomly allocated among the participants. The research subjects, medical assistance, administrative and health staff will not have access to the contents of the bottles. The Arm Lopinavir/ ritonavir plus hydroxychloroquine will receive two of such bottles. At the end of the study, after the statistical analysis and DMSB meeting, it will then be requested from third party documentation on content of each bottle and then have arms identified.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director - Outpatient Research Clinic

Model Details: Patients will be randomly allocated to one of four treatment arms in a 1:1:1:1 ratio: 1. Lopinavir / Ritonavir 2. Hydroxychloroquine 3. Lopinavir / Ritonavir + Hydroxychloroquine 4. Placebo. We will use a centralized random allocation schedule, generated by computer and implemented using an online remote access system. Randomization will be stratified by participating basic health unit.

Study Record Dates

• First Submitted: May 23, 2020
• First Posted: May 27, 2020
• Study Start: June 3, 2020
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: January 26, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (4)