Clinical trial NCT04441385: Study to Evaluate the Efficacy and Safety of Maraviroc in SARS-CoV-2 Infection (COVID-19).
Official title: Bicentric, Phase 2, Randomized, Open-label Study to Evaluate the Efficacy and Safety of Maraviroc Associated With Standard Treatment in Hospitalized Patients With Pulmonary SARS-CoV-2 Infection (COVID-19).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Keywords: SARS-CoV-2
ARDS
Acute respiratory distress syndrome
maraviroc
Lead sponsor: Hospital Universitario Infanta Leonor
Sponsor class: OTHER
Collaborators: name: Hospital Clinic of Barcelona
name: ViiV Healthcare
First posted: 2020-06-22
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a bicentric, phase 2, randomized, open-label study to evaluate the efficacy and safety of maraviroc associated with standard treatment in hospitalized patients with pulmonary SARS-CoV-2 infection (COVID-19).

Detailed description: This is a bicentric, phase 2, randomized, open-label study to evaluate the efficacy and safety of maraviroc associated with standard treatment in hospitalized patients with pulmonary SARS-CoV-2 infection (COVID-19), to prevent disease progression to severe Acute Respiratory Distress Syndrome (ARDS).

Patients will be randomized to receive maraviroc (300 mg BID for 14 days) plus standard treatment, or standard treatment alone.

200 subjects will be enrolled and randomized 1:1 in this study.

Eligibility criteria: Inclusion Criteria:

* 1. Male or female adult ≥ 18 years of age at the time of giving informed consent.
* 2. Subject is hospitalized.
* 3. SARS-CoV-2 infection confirmed by PCR or other commercial or public health tests, in any biological sample obtained up to 4 days prior to randomization, or that meets locally accepted criteria for clinical diagnosis of COVID-19.
* 4. Lung involvement confirmed by at least one of the following criteria:

  1. Radiological infiltrates on imaging test (conventional radiography, computed tomography (CT) or other)
  2. In the absence of radiological infiltrates, an SpO2 \< 95% without oxygen supporting therapy (breathing ambient air), combined with cough, crackles on physical exam, or an LDH \> 300 U/L with no other cause.
* 5. Symptom onset ≤ 8 days prior to randomization.
* 6. Understands and agrees to comply with planned study procedures.
* 7. Women of childbearing potential must have a negative test for pregnancy (blood or urine) before their inclusion and agree to use an accepted method of contraception for the duration of the study.
* 8. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.

Exclusion Criteria:

* 1. SpO2 ≤ 91% breathing ambient air and SpO2 \< 95% with oxygen in nasal cannula at 2 lpm.
* 2. Patient's attending physician considers the study is not the best medical option, or follow-up after discharge will be difficult.
* 3. A patient who, in the investigator's opinion, is unlikely to survive \> 48 hours from inclusion in the study.
* 4. Patients with severe chronic kidney disease (ClCr \< 30 ml/min/1.73 m2 or receiving renal replacement therapy in any of its modalities).
* 5. Severe liver disease (Child-Pugh C, ALT \> 5 times above upper limit of normal (LSN).
* 6. COPD with FEV1 \< 70.
* 7. Known active neoplasia.
* 8. HIV infection. Patients with known HIV infection, under follow-up, and immunovirological stability (CD4\> 500 and undetectable viral load) for at least 6 months before inclusion in this study may be included.
* 9. Hemoglobin \< 9 gr/dL.
* 10. Prolonged QT, defined as a QT interval \> 460 ms. (or \> 450 ms. in case of family history of sudden death or long QT syndrome or personal history of repeat syncope without an etiological diagnosis). This criterion will only apply if the standard treatment contains drugs with an effect on the duration (prolongation) of the QT interval.
* 11.Significant cardiovascular disease, including:

  1. History of acute myocardial infarction, acute coronary syndrome (unstable angina, coronary by-pass surgery, angioplasty, or coronary stenting) ≤ 6 months prior to randomization
  2. Symptomatic heart failure (NYHA grade 2 or more) history, or current evidence of cardiac arrhythmia (except atrial fibrillation or flutter and paroxysmal supraventricular tachycardia) and/or conduction abnormalities (excluding branch blocks or Wenckebach grade I and II atrioventricular blocks).
* 12. Known or suspected active autoimmune disease
* 13. Pregnancy or breastfeeding, or positive pregnancy test at baseline or screening visit
* 14. Patients who are expected to be transferred to another facility sooner than 72 hours after inclusion in the study.
* 15. Patients who have received experimental treatment (off-label, compassionate use, or in clinical trials) within 30 days prior to the screening visit, except for treatment considered standard initiated on admission to hospital, up to 48 hours before inclusion in the study.
* 16. Patients who have a history of allergic reactions to maraviroc or any of its components.

Primary outcomes:
measure: Proportion of patients developing severe ARDS.
timeFrame: 28 days
Secondary outcomes:
measure: All-cause mortality.
timeFrame: 28 days
measure: Percentage of patients requiring tracheal intubation, use of Non-invasive Ventilation NIV or High Flow Nasal Cannula (HFNC) devices during the study period
timeFrame: 28 days
measure: Percentage of patients who progress to severe ARDS, death or ICU admission.
timeFrame: 28 days
measure: Differences in Time to Clinical Improvement
timeFrame: 28 days
measure: Change in clinical status of subject on a 7-point ordinal scale.
timeFrame: 28 days
measure: Percentage of patients requiring immunosuppressive/immunomodulatory treatment as a rescue medication.
timeFrame: 28 days
measure: Proportion of patients developing adverse effects, serious adverse reactions, laboratory or physical examination findings, EKG abnormalities acquired during the trial, death and adverse events leading to early discontinuation of treatment.
timeFrame: 28 days
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
Study officials:
affiliation: Hospital Universitario Infanta Leonor
name: Víctor Domínguez, MD
role: PRINCIPAL_INVESTIGATOR
References: