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

January 25, 2021 updated by: Gilmar Reis, Cardresearch

Hydroxychloroquine and Lopinavir/ Ritonavir for Hospitalization and Mortality Reduction in Patients With COVID-19 and Mild Disease Symptoms: "The Hope Coalition"

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Anticipated)

1968

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Minas Gerais
      • Belo Horizonte, Minas Gerais, Brazil, 30150240
        • Recruiting
        • CARDRESEARCH - Cardiologia Assistencial e de Pesquisa
      • Belo Horizonte, Minas Gerais, Brazil, 30535901
        • Not yet recruiting
        • Pontifícia Universidade Católica de Minas Gerais
        • Contact:
        • Principal Investigator:
          • Eduardo Silva, MD, PhD
      • Betim, Minas Gerais, Brazil, 32600412
        • Recruiting
        • Fundo Municipal de Saúde de Betim
        • Contact:
        • Principal Investigator:
          • Daniela Silva, MD, PhD
      • Ouro Preto, Minas Gerais, Brazil, 35400000
        • Not yet recruiting
        • Universidade Federal de Ouro Preto
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: FACTORIAL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Hydroxychloroquine Sulfate
Hydroxychloroquine 400 mg. Loading oral dose of 800 mg followed by orally dose of 400 mg/ day for the following 10 days
Tablets of 400 mg: Loading dose of 02 tablets followed by one tablet of 400 mg orally on the following 09 days
ACTIVE_COMPARATOR: 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
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
ACTIVE_COMPARATOR: 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

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_COMPARATOR: Placebo

Placebo

Twice a day from day 1 through day 10.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants who were hospitalized for progression of COVID-19 disease
Time Frame: Measuring during 28-day period since randomization (Intention to treat analysis)
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
Time Frame: Measuring during 28-day period since randomization (Intention to treat analysis)
Measuring during 28-day period since randomization (Intention to treat analysis)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants with viral load change on 03, 07, 10 and 14 after randomization
Time Frame: Measuring during 14-day period since randomization
Viral load change on 03, 07, 10 and 14 after randomization (200 patients per arm)
Measuring during 14-day period since randomization
Time to clinical improvement
Time Frame: Measuring during 28-day period since randomization
Proportion of participants with clinical improvement, defined as normalization of temperature, Respiratory rate, SaO2, and cough relief (> 50% compared to baseline measured on a visual analog scale) in the last 72 hours.
Measuring during 28-day period since randomization
Time to clinical failure
Time Frame: Measuring during 28-day period since randomization
Proportion of participants with clinical improvement, defined as as time to need for hospitalization due to dyspnea, death, need for mechanical ventilation, shock and need for vasoactive amines;
Measuring during 28-day period since randomization
Hospitalization for any cause
Time Frame: Measuring during 28-day period since randomization
Proportion of participants with hospitalization for any cause
Measuring during 28-day period since randomization
Proportion of participants who died due to pulmonary complications
Time Frame: Measuring during 28-day period since randomization
Measuring during 28-day period since randomization
Proportion of participants who died due to cardiovascular complications
Time Frame: Measuring during 28-day period since randomization
Measuring during 28-day period since randomization
Proportion of participants who presented with adverse events
Time Frame: Measuring during 28-day period since randomization
Evaluation of adverse events evaluated as associated to any of study arms
Measuring during 28-day period since randomization
Time to improvement on respiratory scale symptoms
Time Frame: Measuring during 28-day period since randomization
Proportion of participants who presented sustained improvement on respiratory scale defined as at least 48 hours of improvement.
Measuring during 28-day period since randomization
proportion of non-adherent participants to any of study drugs
Time Frame: Measuring during 10-day period since randomization
Measuring during 10-day period since randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Gilmar Reis, MD, PhD, Cardresearch - Cardiologia Assistencial e de Pesquisa LTDA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 3, 2020

Primary Completion (ANTICIPATED)

February 1, 2021

Study Completion (ANTICIPATED)

February 1, 2021

Study Registration Dates

First Submitted

May 23, 2020

First Submitted That Met QC Criteria

May 23, 2020

First Posted (ACTUAL)

May 27, 2020

Study Record Updates

Last Update Posted (ACTUAL)

January 26, 2021

Last Update Submitted That Met QC Criteria

January 25, 2021

Last Verified

January 1, 2021

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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