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COVID-19Phase 3NCT04403100

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

A Phase 3 study testing Hydroxychloroquine Sulfate Tablets, Lopinavir/ Ritonavir Oral Tablet and Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets in people with COVID-19 and Coronavirus Infection, run by Cardresearch at 4 sites in Brazil.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
COVID-19, Coronavirus Infection, Virus Disease
What is being tested?
Hydroxychloroquine Sulfate Tablets, Lopinavir/ Ritonavir Oral Tablet and Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,968 participants
Where
4 sitesBrazil
Study dates
3 Jun 2020to 1 Feb 2021
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with RT-PCR diagnosis of COVID-19 or a clinical condition compatible with COVID-19 and respiratory symptoms, presenting:
  • Persistent dry cough associated with axillary temperature > 37.7 Celsius;
  • OR
  • Recent onset of Flu-like Respiratory Symptoms associated with dry cough
  • OR
  • Tomographic image compatible with COVID 19 infection;
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  • 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.

Who cannot join

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

Trial locations and contacts

4 sites in 1 country.

Gilmar Reis, MD, PhD contact

+5531332416574

greisbh@uol.com.br

Rosemary Oliveira, SC contact

+5531992636703

roliveira@cardresearch.org

Brazil4 sites, 4 recruiting
  • CARDRESEARCH - Cardiologia Assistencial e de Pesquisa

    Belo Horizonte, Minas Gerais, 30150240

    Izabel Silva, SC, 553132416574, coordpesq@cardresearch.org

    Gilmar Reis, MD,PhD

    Recruiting
  • Pontificia Universidade Catolica de Minas Gerais

    Belo Horizonte, Minas Gerais, 30535901

    Eduardo Silva, MD, PhD, duduaugusto1@gmail.com

    Eduardo Silva, MD, PhD

    Not yet recruiting
  • Fundo Municipal de Saúde de Betim

    Betim, Minas Gerais, 32600412

    Daniela Silva, MD, PhD, 5531984923130, daninhamed@yahoo.com.br

    Daniela Silva, MD, PhD

    Recruiting
  • Universidade Federal de Ouro Preto

    Ouro Preto, Minas Gerais, 35400000

    Leonardo Savassi, MD, PhD, leosavassi@gmail.com

    Leonardo Savassi, MD, PhD

    Not yet recruiting

Other trials in Brazil

About this study

Official title: 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.

Read the 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.

Being tested
Hydroxychloroquine Sulfate Tablets, Lopinavir/ Ritonavir Oral Tablet, Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets, Placebo
Medical subject headings
COVID-19, Coronavirus Infections, Virus Diseases, Severe Acute Respiratory Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hydroxychloroquine Sulfate TabletsDrug

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

  • Lopinavir/ Ritonavir Oral TabletDrug

    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 Sulfate Tablets plus Lopinavir/ Ritonavir Oral TabletsDrug

    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

  • PlaceboDrug

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

Study groups in NCT04403100
Study groupRoleWhat they receive
Hydroxychloroquine SulfateActive comparatorHydroxychloroquine 400 mg. Loading oral dose of 800 mg followed by orally dose of 400 mg/ day for the following 10 days
Receives: Drug: Hydroxychloroquine Sulfate Tablets
Lopinavir/ RitonavirActive comparatorLopinavir 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
Receives: Drug: Lopinavir/ Ritonavir Oral Tablet
Hydroxychloroquine plus Lopinavir/ RitonavirActive comparatorHydroxychloroquine 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
Receives: Drug: Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets
PlaceboPlacebo comparatorPlacebo Twice a day from day 1 through day 10.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

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

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

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

Secondary outcomes (9)
  1. Proportion of participants with viral load change on 03, 07, 10 and 14 after randomization

    Viral load change on 03, 07, 10 and 14 after randomization (200 patients per arm)

    Measured: Measuring during 14-day period since randomization

  2. Time to clinical improvement

    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.

    Measured: Measuring during 28-day period since randomization

  3. Time to clinical failure

    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;

    Measured: Measuring during 28-day period since randomization

  4. Hospitalization for any cause

    Proportion of participants with hospitalization for any cause

    Measured: Measuring during 28-day period since randomization

  5. Proportion of participants who died due to pulmonary complications

    Measured: Measuring during 28-day period since randomization

  6. Proportion of participants who died due to cardiovascular complications

    Measured: Measuring during 28-day period since randomization

  7. Proportion of participants who presented with adverse events

    Evaluation of adverse events evaluated as associated to any of study arms

    Measured: Measuring during 28-day period since randomization

  8. Time to improvement on respiratory scale symptoms

    Proportion of participants who presented sustained improvement on respiratory scale defined as at least 48 hours of improvement.

    Measured: Measuring during 28-day period since randomization

  9. proportion of non-adherent participants to any of study drugs

    Measured: Measuring during 10-day period since randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 May 2020
  2. Study start3 Jun 2020
  3. Primary completion1 Feb 2021 (estimated)
  4. Study completion1 Feb 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,968 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04403100
Sponsor's protocol ID
COVID19_AMB_Brasil
Status last verified
Jan 2021
First submitted
23 May 2020
Last updated
26 Jan 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33885775

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Hydroxychloroquine Sulfate Tablets, Lopinavir/ Ritonavir Oral Tablet and Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets in people with COVID-19 and Coronavirus Infection, run by Cardresearch at 4 sites in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 26 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Gilmar Reis, MD, PhD (+5531332416574, greisbh@uol.com.br), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04403100, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2021.

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