mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Repurposed Drugs (TACTIC-R)
- Registration Number
- NCT04390464
- Brief Summary
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.
- Detailed Description
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:
1. Stratify patients to therapeutic arms according to probability of efficacy
2. 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 1167
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard of care Standard of care Standard of care Baricitinib + Standard of care Baricitinib Baricitinib PO OD (4mg, Days 1-14) Ravulizumab + Standard of care Ravulizumab Ravulizumab IV (adjusted to weight, Day 1 only)
- Primary Outcome Measures
Name Time Method Time to incidence of the composite endpoint of: Death, Mechanical ventilation, ECMO, Cardiovascular organ support, or Renal failure 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
- Secondary Outcome Measures
Name Time Method Change in clinical status as assessed on 7-point ordinal scale compared to baseline 14 days The clinical status of the patients is assessed using 7-point ordinal scale as follows: 1 = Death, 2 = Mechanical ventilation, 3 = Non-invasive or high flow oxygen, 4 = Low flow oxygen, 5 = Hospitalised - no oxygen, 6 = Discharged - normal activities not resumed, 7 = Discharged - normal activities resumed
Proportion of patients with adverse events of special interest in each treatment arm 14 days The proportion of patients in each treatment arm that experience adverse events of special interest, defined as: venous thromboembolism, new infections requiring antimicrobials
Time to Sp02 >94% on room air 14 days The time taken to achieve blood oxygen saturation levels above 94% in patients on room air, measured in hours/days
Time to first negative SARS-CoV2 PCR 14 days The amount of time between a patient's first positive SARS-CoV2 PCR test and a patient's first negative SARS-CoV2 PCR test, measured in days
Duration of oxygen therapy 14 days The duration of oxygen therapy given to a patient, measured in days
Duration of hospitalisation 14 days The duration of hospitalisation of a patient, measured in days
All cause mortality at day 28 28 Days The number of deaths recorded at 28 days irrespective of the cause
Time to clinical improvement 14 days The time to clinical improvement for a patient, defined as: \>2 point improvement from Day 1 on the 7-point ordinal scale, measured in days
Trial Locations
- Locations (1)
Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, Cambridgeshire, United Kingdom