Phase 3 Randomized, Double-blind, Placebo-controlled Multi-center Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm (RUXCOVID)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 432
- 试验地点
- 1
- 主要终点
- Proportion of Patients Who Die, Develop Respiratory Failure [Require Mechanical Ventilation] or Require Intensive Care Unit (ICU) Care
研究概览
简要总结
This was a randomized, double-blind, placebo-controlled, 29-day, multicenter study to assess the efficacy and safety of ruxolitinib + standard-of-care (SoC) therapy, compared with placebo + SoC therapy, in patients aged ≥12 years with COVID-19 disease.
详细描述
This was a Phase III, multicenter, double-blind, randomized, placebo-controlled study to assess the efficacy and safety of ruxolitinib in patients aged ≥12 years with COVID-19 disease. The study enrolled patients to ruxolitinib or placebo, in addition to standard of care (SoC) per local practice. Patients who meet the inclusion/exclusion criteria were randomized in a 2:1 ratio to either oral ruxolitinib 5 mg twice daily + SoC or oral matching-image placebo + SoC for a total of 14 days. An additional 14 days of study drug could be given if in the opinion of the investigator the patient's clinical signs and symptoms did not improve, or worsen, and the potential benefit outweighed the potential risk.
The study included:
- Screening period of 0-2 days.
- Study period of 29 days (treatment of 14 days with possible extension of treatment to 28 days).
The primary objective was to evaluate the efficacy (as measured by a composite endpoint of proportion of patients who die, develop respiratory failure [require mechanical ventilation], or require intensive care unit care) of ruxolitinib + standard-of-care (SoC) therapy compared with placebo + SoC therapy, for the treatment of COVID-19 by Day 29.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient or guardian/health proxy must provide informed consent (and assent if applicable) before any study assessment is performed.
- •Male and female patients aged ≥ 12 years (or ≥ the lower age limit allowed by Health Authority and/or Ethics Committee/Institutional Review Board approvals).
- •Patients with coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test or another rapid test from the respiratory tract prior to randomization.
- •Patients currently hospitalized or will be hospitalized prior to randomization.
- •Patients, who meet at least one of the below criteria:
- •Pulmonary infiltrates (chest X ray or chest CT scan);
- •Respiratory frequency ≥ 30/min;
- •Requiring supplemental oxygen;
- •Oxygen saturation ≤ 94% on room air;
- •Arterial oxygen partial pressure (PaO2)/ fraction of inspired oxygen (FiO2) < 300mmHg (1mmHg=0.133kPa) (corrective formulation should be used for higher altitude regions (over 1000m).
排除标准
- •History of hypersensitivity to any drugs or metabolites of similar chemical classes as ruxolitinib.
- •Presence of severely impaired renal function defined by serum creatinine > 2 mg/dL (>176.8 μmol/L), or have estimated creatinine clearance < 30 ml/min measured or calculated by Cockroft Gault equation or calculated by the updated bedside Schwartz equation.
- •Suspected uncontrolled bacterial, fungal, viral, or other infection (besides COVID-19).
- •Currently intubated or intubated between screening and randomization. In intensive care unit (ICU) at time of randomization. Intubated or in ICU for COVID-19 disease prior to screening. Patients who are on anti-rejection, immunosuppressant or immunomodulatory drugs (i.e. tocilizumab, ruxolitinib, canakinumab, sarilumab, anakinra).
- •Unable to ingest tablets at randomization. Pregnant or nursing (lactating) women
研究组 & 干预措施
Ruxolitinib 5 mg
Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days
干预措施: Ruxolitinib (Drug)
Placebo
Matching-image placebo for 14 days with possible extension of treatment to 28 days
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of Patients Who Die, Develop Respiratory Failure [Require Mechanical Ventilation] or Require Intensive Care Unit (ICU) Care
时间窗: Day 1 - Day 29
Efficacy is measured by a composite endpoint of proportion of patients who die, develop respiratory failure \[require mechanical ventilation\], or require intensive care unit \[ICU\] care for the treatment of COVID-19. Analyses are cumulative, thus analysis on Day 29 includes all events till that day. Patients who developed respiratory failure and/or required ICU at randomization are excluded from the analysis.
次要结局
- Clinical Status(Baseline, Day 15, Day 29)
- Percentage of Patients With at Least Two-point Improvement From Baseline in Clinical Status(Baseline, Day 15, Day 29)
- Percentage of Patients With at Least One-point Improvement From Baseline in Clinical Status(Baseline, Day 15, Day 29)
- Percentage of Patients With at Least One-point Deterioration From Baseline in Clinical Status(Baseline, Day 15, Day 29)
- Mortality Rate(Day 15, Day 29)
- Mean Change From Baseline in the Clinical Status(Baseline, Day 15, Day 29)
- Time to Improvement in Clinical Status(29 days)
- Proportion of Patients Requiring Mechanical Ventilation(Day 1 - Day 29)
- Duration of Hospitalization(29 days)
- Time to Hospital Discharge or to a NEWS2 Score of ≤2(29 days)
- Change From Baseline in NEWS2 Score(Baseline, Days 3, 5, 8, 11, 15, and 29)
- Change From Baseline in SpO2/FiO2 Ratio(Baseline, Day 15, Day 29)
- Proportion of Patients With no Oxygen Therapy(Day 15, Day 29)