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).
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Proportion of patients developing severe ARDS.
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female adult ≥ 18 years of age at the time of giving informed consent.
- •Subject is hospitalized.
- •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-
- •Lung involvement confirmed by at least one of the following criteria:
- •Radiological infiltrates on imaging test (conventional radiography, computed tomography (CT) or other)
- •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.
- •Symptom onset ≤ 8 days prior to randomization.
- •Understands and agrees to comply with planned study procedures.
- •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.
- •Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
排除标准
- •SpO2 ≤ 91% breathing ambient air and SpO2 < 95% with oxygen in nasal cannula at 2 lpm.
- •Patient's attending physician considers the study is not the best medical option, or follow-up after discharge will be difficult.
- •A patient who, in the investigator's opinion, is unlikely to survive > 48 hours from inclusion in the study.
- •Patients with severe chronic kidney disease (ClCr < 30 ml/min/1.73 m2 or receiving renal replacement therapy in any of its modalities).
- •Severe liver disease (Child-Pugh C, ALT > 5 times above upper limit of normal (LSN).
- •COPD with FEV1 <
- •Known active neoplasia.
- •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.
- •Hemoglobin < 9 gr/dL.
- •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:
- •History of acute myocardial infarction, acute coronary syndrome (unstable angina, coronary by-pass surgery, angioplasty, or coronary stenting) ≤ 6 months prior to randomization
- •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).
- •Known or suspected active autoimmune disease
- •Pregnancy or breastfeeding, or positive pregnancy test at baseline or screening visit
- •Patients who are expected to be transferred to another facility sooner than 72 hours after inclusion in the study.
- •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.
- •Patients who have a history of allergic reactions to maraviroc or any of its components.
研究组 & 干预措施
Test arm
100 subjects will be randomly assigned to this arm. Patients in the test group will receive 300 mg of maraviroc BID for 14 days (added to standard care).
干预措施: Maraviroc 300 mg (Drug)
Control arm
100 subjects will be randomized in this arm and will be treated according to the standard care. The Ministry of Health has issued detailed guidelines for the management of COVID-19. Local Institutional Guidelines and Protocols for supportive management will also be implemented.
干预措施: Standard care therapy (Other)
结局指标
主要结局
Proportion of patients developing severe ARDS.
时间窗: 28 days
A patient with a saturation of 90% or less despite the use of a reservoir mask without rebreathing with a flow of 7 liters per minute (FiO2 0.6 or higher), will be considered to have severe ARDS. These oximetric criteria have a close correlation with a PaO2 / FiO2 of 100 or less, which defines severe ARDS.
次要结局
- All-cause mortality.(28 days)
- Percentage of patients requiring tracheal intubation, use of Non-invasive Ventilation NIV or High Flow Nasal Cannula (HFNC) devices during the study period(28 days)
- Percentage of patients who progress to severe ARDS, death or ICU admission.(28 days)
- Percentage of patients requiring immunosuppressive/immunomodulatory treatment as a rescue medication.(28 days)
- 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.(28 days)
- Differences in Time to Clinical Improvement(28 days)
- Change in clinical status of subject on a 7-point ordinal scale.(28 days)