mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Repurposed Drugs (TACTIC-R)
试验速览
- 阶段
- 4 期
- 入组人数
- 1,167
- 试验地点
- 1
- 主要终点
- Time to incidence of the composite endpoint of: Death, Mechanical ventilation, ECMO, Cardiovascular organ support, or Renal failure
研究概览
简要总结
TACTIC-R is a randomised, parallel arm, open-label platform trial for investigating potential treatment for COVID-19 disease. While SARS-CoV infection evades detection by the immune system in the first 24 hours of infection, it ultimately produces a massive immune system response in the subgroup of people who develop severe complications. Most tissue damage following infection with COVID19 appears to be due to a later, exaggerated, host immune response. This leads to lung and sometimes multi-organ damage.
Most people who develop these severe complications still have virus present in their respiratory tract at the time-point when the disease starts to evolve. Immune modulation in the presence of active infection has potential to cause more harm than benefit. Safety considerations when studying immune modulation strategies are paramount. Therefore, this study proposes to assess the efficacy of immunomodulatory agents that target dysregulated immune response that drive the severe lung, and other organ, damage. The medications investigated for efficacy in this trial are Baricitinib and Ravulizumab.
详细描述
TACTIC-R will assess the efficacy of the immunomodulatory agents Baricitinib and Ravulizumab as potential treatments for COVID-19 disease against Standard of Care alone. These agents target the dysregulated immune response that drives the severe lung, and other organ, damage frequently seen during COVID-19 infection. This trial will compare these immunomodulatory agents to Standard of Care over a 14-day treatment period, with follow-up at 28 and 90 days. Patients will be randomised in a 1:1:1 ratio across treatments.
TACTIC-R will use a platform design with interim analysis to make efficient decisions about efficacy and futility (e.g. lack of efficacy and risk of harm) of the trial treatments. This enables the trial to stop recruiting to arms early where a clear efficacy decision can be made. It also allows for the addition of further arms.
TACTIC-R will also iterate an algorithm for use of clinical and biochemical phenotyping to:
- Stratify patients to therapeutic arms according to probability of efficacy
- Identify early indicators of failure of therapeutic strategy.
By collecting samples for genomics, transcriptomics, proteomics and immunological phenotyping, parallel studies associated with TACTIC-R will investigate host susceptibility factors for development of severe COVID-19-related disease and predictive biomarkers of response to therapeutic strategy.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Standard of care
Standard of care
干预措施: Standard of care (Other)
Ravulizumab + Standard of care
Ravulizumab IV (adjusted to weight, Day 1 only)
干预措施: Ravulizumab (Drug)
Baricitinib + Standard of care
Baricitinib PO OD (4mg, Days 1-14)
干预措施: Baricitinib (Drug)
结局指标
主要结局
Time to incidence of the composite endpoint of: Death, Mechanical ventilation, ECMO, Cardiovascular organ support, or Renal failure
时间窗: up to Day 14
Number of days taken for occurrence of one of the following events: 1. Death 2. Mechanical ventilation 3. Extracorporeal membrane oxygenation (ECMO) 4. Cardiovascular organ support (balloon pump or inotropes) 5. Renal failure (estimated creatinine clearance (by Cockcroft-Gault formula) \<15 ml /min/1.73m\^2), haemofiltration or dialysis
次要结局
- Change in clinical status as assessed on 7-point ordinal scale compared to baseline(14 days)
- Proportion of patients with adverse events of special interest in each treatment arm(14 days)
- Time to Sp02 >94% on room air(14 days)
- Time to first negative SARS-CoV2 PCR(14 days)
- Duration of oxygen therapy(14 days)
- Duration of hospitalisation(14 days)
- All cause mortality at day 28(28 Days)
- Time to clinical improvement(14 days)
研究者
Frances Hall
Consultant Rheumatologist
Cambridge University Hospitals NHS Foundation Trust