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COVID-19Phase 2COMVIVIRNCT04475991

Safety and Efficacy of Maraviroc and/or Favipiravir With Standard Therapy in Severe COVID-19 Adults

A Phase 2 study testing Maraviroc + Currently used therapy, Curently used therapy for COVID-19 non-critical patients and Favipiravir + Currently used therapy in people with COVID-19, run by Hospital General de México Dr. Eduardo Liceaga at 1 site in Mexico.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Phase 2, randomized, open-label study to evaluate the safety and efficacy of maraviroc, favipiravir, and both drugs administered along with currently used therapy in hospitalized patients with pulmonary SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection (COVID-19) Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
COVID-19
What is being tested?
Maraviroc + Currently used therapy, Curently used therapy for COVID-19 non-critical patients and Favipiravir + Currently used therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteMexico
Study dates
13 Jul 2021to 25 Mar 2022
Phase
Phase 2
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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • With severe non-critical stage of COVID at the time of admission.
  • Patients tested positive for SARS-CoV-2 confirmed by PCR (Polymerase Chain Reaction) or quick antigen test
  • Within the first 12 days post appearance of symptoms
  • With at least one of the following risk factors: Diabetes mellitus (DM), obesity (BMI>30, hypertension, age > 65 years.
  • Respiratory rate 25-34/min and no signs of respiratory distress.
  • With at least two of the following indicators of severity: SpO2 81-90%, PaFi 150-300 mmHg, FiO2>60% , lung damage in thorax radiographic image => 25% as determined by RALE score (an equivalent to 2-4).
  • Normal liver function (Considered up to a fivefold increase above the normal limits of hepatic transaminases)
  • Signed informed consent

Who cannot join

  • Pregnant or lactating women
  • Patients already participating in another clinical study
  • Oxygen saturation < 70% (ambient)
  • Clinical evidence of an infectious disease different from COVID at the time of admission
  • Chronic kidney failure
  • Coronary disease
Show all 18Show fewer
  • Glomerular filtration rate < 30ml/min/1.73 m2 and known history of preexisting chronic renal failure (Chronic kidney disease stages 4-5)
  • Known history of HCV, HBV and/or clinical signs of hepatic liver failure.
  • Any type of cancer
  • HIV and/or any anti retroviral treatment
  • Inability to freely decide to participate
  • Psychotropics treatment
  • Erythromycin treatment
  • Polydrug use (Defined as more than two addictions combined)
  • With transplant background
  • With any autoimmune disorder
  • With known hypersensibility to maraviroc and/or favipiravir
  • On invasive mechanical ventilation at the time of randomization

Trial locations and contacts

1 site in 1 country.

Mexico1 site

  • Hospital General de México "Dr. Eduardo Liceaga"

    Mexico City, Mexico City, 06720

Other trials in Mexico

About this study

Official title: Phase2, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Maraviroc and/or Favipiravir Plus Standard Therapy in Adult Patients With Severe Non-critical COVID-19"

Phase 2, randomized, open-label study to evaluate the safety and efficacy of maraviroc, favipiravir, and both drugs administered along with currently used therapy in hospitalized patients with pulmonary SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection (COVID-19)

Read the detailed description

The COVID-19 pandemic (Coronavirus Disease-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has caused more that 10 million infections worldwide, with a general mortality of 6%. Multiple studies have found that the hyperinflammatory immune response induced by SARS-CoV-2 is one of the main causes of severity and death in infected patients. In severe COVID-19 patients, an association was found between pneumonitis and/or ARDS (Acute Severe Respiratory Syndrome), increased serum levels of cytokines and chemokines, extensive lung damage and microthrombosis. Studies of both gene expression in lungs and blood cytokines and chemokines have related chemokine signaling clusters with COVID-19 severity, being CCL3, CCL4 and CCL7 (CC chemokine ligands 3, 4 and 7) particularly interesting. All these are CCR5 (CC chemokine receptor 5) ligands. A strategy to modulate activation and trafficking of leukocytes to the lungs is by blocking CCR5 by using maraviroc (MVC), which has shown capable of modulating conditions of generalized inflammation. Along with a good regulation of the immune response, an antiviral that helps to reduce the viral load must be considered. Favipiravir (FPV) has shown to be capable to reduce the time of viral clearance by half. Hence, we propose that the conjoint use of MVC and FPV could help to reduce the progression of severe hospitalized COVID-19 patients to critical by decreasing the percentage of patients in need of mechanical respiratory support or death by at least 30%. This is a randomized, controlled clinical trial that besides evaluating the safety and efficacy of MVC+FPV to avoid progression in severe COVID-19 patients as a primary endpoint, is also aimed at other secondary endpoints: A) Evaluate the activation of CCR5 in peripheral blood lymphocytes, monocytes, and neutrophils. B) Find possible modifications in the ongoing chemokine and cytokine storm in serum, particularly IL-6, IL-1b, (interleukins 6 and 1 beta) TNF (tumor necrosis factor), IFNa, IFNg (interferons alpha and gamma), VEGF (vascular endothelial growth factor), CXCL10 (CXC chemokine ligand 10), CCL7, CCL3, and CCL5 (CC chemokine ligands 7, 3 and 5), C) Search for alterations in the patterns of activation, trafficking, and exhaustion of peripheral blood lymphocytes, monocytes and neutrophils, and D) Determine if it has an effect in viral loads in saliva. 100 severe patients tested positive for SARS-CoV-2 will be randomized in 4 treatment arms:

Arm A: Currently used therapy (CT) only, Enoxaparin, dexamethasone, and antibiotics if associated bacteremia is present, as per currently used at Hospital General de México "Dr. Eduardo Liceaga").

Arm B: CT+MVC Arm C: CT+FPV Arm D: CT+MVC+FPV

Conditions
COVID-19
Being tested
Maraviroc + Currently used therapy, Curently used therapy for COVID-19 non-critical patients, Favipiravir + Currently used therapy, Maraviroc+Favipiravir+CT
Keywords
COVID-19, CCR5, Cytokine storm, Maraviroc, Favipiravir, RdRP inhibitors
Medical subject headings
COVID-19, Cytokine Release Syndrome

What participants receive

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

  • Maraviroc + Currently used therapyDrug

    Also called MVC+CT

    Maraviroc tablets. 300 mg bid, given orally for a 10 day period AND CT (Enoxaparin, dexamethasone, and antibiotics if associated bacteremia is present, as per currently used at Hospital General de México "Dr. Eduardo Liceaga")

  • Curently used therapy for COVID-19 non-critical patientsProcedure or surgery

    Also called CT only

    Enoxaparin, dexamethasone, and antibiotics if associated bacteremia is present, as per currently used at Hospital General de México "Dr. Eduardo Liceaga"

  • Favipiravir + Currently used therapyDrug

    Also called FPV+CT

    Favipiravir tablets 200 mg. given orally for a 7 day period. 1600 mg bid on day 1 and 600 mg tid days 2-7 AND CT (Enoxaparin, dexamethasone, and antibiotics if associated bacteremia is present, as per currently used at Hospital General de México "Dr. Eduardo Liceaga").

  • Maraviroc+Favipiravir+CTDrug

    Also called MVC+FPV+CT

    Maraviroc tablets. 300 mg bid, given orally for a 10 day period AND Favipiravir tablets 200 mg. given orally for the first 7 days. 1600 mg bid on day 1 and 600 mg tid days 2-7 AND CT (Enoxaparin, dexamethasone, and antibiotics if associated bacteremia is present, as per currently used at Hospital General de México "Dr. Eduardo Liceaga"")

Study groups in NCT04475991
Study groupRoleWhat they receive
Currently used therapy (CT) onlyActive comparatorTreatment currently used at Hospital General de México "Dr. Eduardo Liceaga" for non-critical COVID patients: Enoxaparin, dexamethasone, and antibiotics if associated bacteremia is present.
Receives: Procedure: Curently used therapy for COVID-19 non-critical patients
Maraviroc+CTExperimentalMaraviroc AND treatment currently used at Hospital General de México "Dr. Eduardo Liceaga" for non-critical COVID patients.
Receives: Drug: Maraviroc + Currently used therapy
Favipiravir+CTExperimentalFavipiravir AND treatment currently used at Hospital General de México "Dr. Eduardo Liceaga" for non-critical COVID patients.
Receives: Drug: Favipiravir + Currently used therapy
Maraviroc+Favipiravir+CTExperimentalMaraviroc AND Favipiravir AND treatment currently used at Hospital General de México "Dr. Eduardo Liceaga" for non-critical COVID patients
Receives: Drug: Maraviroc+Favipiravir+CT

What is being measured

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

  1. Patients free of mechanical ventilation or death

    Percentage of patients free of mechanical ventilation or death

    Measured: 28 days post start

Secondary outcomes (5)

  1. Patients free of mechanical ventilation or death

    Percentage of patients free of mechanical ventilation or death

    Measured: 5 days post start

  2. Time of clinical improvement

    Time of improvement in at least 2 items of the 8-item World Health Organization (WHO) ordinal scale for COVID-19 in days.

    Measured: 15 days post start

  3. Rate of change in phosphorylated CCR5

    Rate of change (Delta) in lymphocytes, monocytes and neutrophils with phosphorylated CCR5 as per measured by parameters of flow cytometry.

    Measured: Day 10-1

  4. Rate of change in peripheral blood levels of proinflammatory cytokines and chemokines

    Rate of change (Delta) in peripheral blood levels of proinflammatory cytokines and chemokines [IL-6, IL-1b, TNF, IFNa, IFNg, VEGF, GM-CSF (granulocyte-macrophage colony stimulating factor), CCL2, CCL3, CCL4, CCL5, CXCL10 and CCL7], as per measured by parameters of flow cytometry

    Measured: Day 10-1

  5. Change in the trafficking and activation pattern of peripheral leukocytes

    Statistically significant change in the expression of activation [phosphorylated CCR5,CD38, CD126, CD127, CD25, CD86, CD83, CD40 (clusters of differentiation 38, 126, 127, 25, 86 and 40), HLA-DR (Human Leukocyte Antigen-DR isotype), Granzyme B, Perforin, CD107A, CD123, gp130, CD95], trafficking [CCR5, CCR2, CCR6, CCR7, CXCR1, CXCR3 , CXCR5, (CXC chemokine receptors 1, 3 and 5), CX3CR1 (CX3C chemokine receptor] and exhaustion (PD1, programmed death-1 receptor) markers in peripheral blood lymphocytes, neutrophils and monocytes, as per measured by parameters of flow cytometry.

    Measured: Day 10-1

Timeline

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

  1. First posted17 Jul 2020
  2. Study start13 Jul 2021
  3. Primary completion15 Mar 2022
  4. Study completion25 Mar 2022

Why it stopped: No more patients complying the selection criteria were available for recruitment

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
100 participants will be included and allocated in 4 groups of 25 each \[Currently used therapy (CT), Maraviroc+CT, Favipiravir+CT and Maraviroc+Favipiravir+CT\]. Subjects will be randomized using EPIDAT 4.2
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04475991
Sponsor's protocol ID
DI/20/407/04/38
Acronym
COMVIVIR
Status last verified
May 2022
First submitted
15 Jul 2020
Last updated
3 Jun 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Inter-institutional exchange of data

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Maraviroc + Currently used therapy, Curently used therapy for COVID-19 non-critical patients and Favipiravir + Currently used therapy in people with COVID-19, run by Hospital General de México Dr. Eduardo Liceaga at 1 site in Mexico.

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 8 inclusion and 18 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: stopped early, as of the sponsor's last update on 3 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Mexico. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study was stopped early (reason given: No more patients complying the selection criteria were available for recruitment). Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Patients free of mechanical ventilation or death (time frame: 28 days post start). 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 NCT04475991.

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 3 Jun 2022.

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