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

NCT ID: NCT04403100

Last Updated: 2021-01-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 1968 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-03
• Study Completion Date: 2021-02-01

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.

Detailed Description

In December 2019 a series of viral pneumonia cases were reported in the city of Wuhan, China. A new subtype of coronavirus has been identified as the causative agent of this condition. On February 11, 43,103 cases had already been described and on this day the World Health Organization (WHO) named this disease as COVID-19. With. The disease had spread out to several countries on different continents and on March 11, WHO declared a state of worldwide pandemic. Today (April 25, 2020) there are 2,719,897 cases and 187,705 deaths documented, with a global case-fatality ratio of 6.9%.

To date, no treatment has been identified as effective in combating this disease which has been identified as with high mortality, therefore there are no specific therapeutic options. So far, efforts have been focused on the treatment of patients hospitalized with dyspnea and, although several promising drugs are being evaluated, none has demonstrated effectiveness in reducing morbidity and mortality at this stage of the disease, suggesting that perhaps the best time to use medications either before the onset of severe symptoms of respiratory distress.

Thus, we propose the use of two drugs which experimentally have shown activity against SARS-CoV2 and being used in severely ill patients with COVID-19. Our hypothesis is that perhaps using such drugs before onset of complications will allow better outcomes on this patient population.

Conditions

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

Study Design

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

Study Groups

Hydroxychloroquine Sulfate

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

Group Type: ACTIVE_COMPARATOR

Hydroxychloroquine Sulfate Tablets

Intervention Type: DRUG

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

Lopinavir/ Ritonavir

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

Group Type: ACTIVE_COMPARATOR

Lopinavir/ Ritonavir Oral Tablet

Intervention Type: 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

Hydroxychloroquine plus Lopinavir/ Ritonavir

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

Group Type: ACTIVE_COMPARATOR

Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets

Intervention Type: 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

Placebo

Placebo

Twice a day from day 1 through day 10.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Hydroxychloroquine Sulfate Tablets

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

Intervention Type: DRUG

Lopinavir/ Ritonavir Oral Tablet

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

Intervention Type: DRUG

Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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;

OR

B. Recent onset of Flu-like Respiratory Symptoms associated with dry cough

OR

C. Tomographic image compatible with COVID 19 infection;

2. 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

3. Ability to provide informed consent before any protocol-related procedures.

Exclusion Criteria

1. RT-PCR exam for COVID-19 negative during the screening visit.

2. Patients with an acute respiratory condition compatible with COVID-19 being hospitalized;

3. Patients with an acute respiratory condition and with moderate to high probability of not being a COVID infection 19;

4. Dyspnea secondary to other acute and chronic respiratory causes or infections (eg, decompensated Chronic Obstructive Pulmonary Disease, acute bronchitis, pneumonia, primary pulmonary arterial hypertension);

5. Severe respiratory clinical condition, presenting at least ONE of the criteria below:

1. Respiratory Rate> 28 / min;

2. Arterial Oxygen Saturation < 92% with nasal oxygen therapy at 10 l/ min;

3. PaO2 / FIO2 <300 mmHg

4. 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

-

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

Sponsors

Cardresearch - Cardiologia Assistencial e de Pesquisa LTDA

UNKNOWN

Sponsor Role: collaborator

Cytel Inc.

INDUSTRY

Sponsor Role: collaborator

Cardresearch

OTHER

Sponsor Role: lead

Responsible Party

Gilmar Reis

Director - Outpatient Research Clinic

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gilmar Reis, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cardresearch - Cardiologia Assistencial e de Pesquisa LTDA

Locations

CARDRESEARCH - Cardiologia Assistencial e de Pesquisa

Belo Horizonte, Minas Gerais, Brazil

Site Status: RECRUITING

Pontificia Universidade Catolica de Minas Gerais

Belo Horizonte, Minas Gerais, Brazil

Site Status: NOT_YET_RECRUITING

Fundo Municipal de Saúde de Betim

Betim, Minas Gerais, Brazil

Site Status: RECRUITING

Universidade Federal de Ouro Preto

Ouro Preto, Minas Gerais, Brazil

Site Status: NOT_YET_RECRUITING

Countries

Brazil

Central Contacts

Gilmar Reis, MD, PhD

Role: CONTACT

greisbh@uol.com.br

+5531332416574

Rosemary Oliveira, SC

Role: CONTACT

roliveira@cardresearch.org

+5531992636703

Facility Contacts

Izabel Silva, SC

Role: primary

coordpesq@cardresearch.org

553132416574

Eduardo Silva, MD, PhD

Role: primary

duduaugusto1@gmail.com

Daniela Silva, MD, PhD

Role: primary

daninhamed@yahoo.com.br

5531984923130

Leonardo Savassi, MD, PhD

Role: primary

leosavassi@gmail.com

References

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.

Reference Type: DERIVED

PMID: 33885775 (View on PubMed)

Other Identifiers

COVID19_AMB_Brasil

Identifier Type: -

Identifier Source: org_study_id