mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Repurposed Drugs (TACTIC-R) (TACTIC-R)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04390464|
Recruitment Status : Recruiting
First Posted : May 15, 2020
Last Update Posted : May 18, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|COVID19||Drug: Ravulizumab Drug: Baricitinib Other: Standard of care||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1167 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||TACTIC-R is a randomised, parallel arm, open-label platform trial.|
|Masking:||None (Open Label)|
|Official Title:||mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Repurposed Drugs (TACTIC-R)|
|Actual Study Start Date :||May 8, 2020|
|Estimated Primary Completion Date :||May 7, 2021|
|Estimated Study Completion Date :||May 1, 2022|
Active Comparator: Standard of care
Standard of care
Other: Standard of care
Regular standard of care for COVID-19 patients
Experimental: Ravulizumab + Standard of care
Ravulizumab IV (adjusted to weight, Day 1 only)
Ravulizumab (Ultomiris, Alexion Pharmaceuticals) is a monoclonal antibody that binds to terminal complement protein C5 and prevents the complement‐mediated destruction of cells. It is administered by intravenous infusion. Ravulizumab has a marketing authorisation in the UK for treating Paroxysmal Nocturnal Haemoglobinuria in adults.
Other Name: Ultomiris
Experimental: Baricitinib + Standard of care
Baricitinib PO OD (4mg, Days 1-14)
Baricitinib is administered orally once daily. It is licensed for treatment of rheumatoid arthritis, it is a relatively fast acting disease modifying anti-rheumatic drug and has the potential to be scaled up for use for a pandemic.
Other Name: Olumiant
- Time to incidence of the composite endpoint of: Death, Mechanical ventilation, ECMO, Cardiovascular organ support, or Renal failure [ Time Frame: 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
- Change in clinical status as assessed on 7-point ordinal scale compared to baseline [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 14 days ]The duration of oxygen therapy given to a patient, measured in days
- Duration of hospitalisation [ Time Frame: 14 days ]The duration of hospitalisation of a patient, measured in days
- All cause mortality at day 28 [ Time Frame: 28 Days ]The number of deaths recorded at 28 days irrespective of the cause
- Time to clinical improvement [ Time Frame: 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04390464
|Contact: Elena Hernan-Sancho||01223 349132 ext firstname.lastname@example.org|
|Cambridge University Hospitals NHS Foundation Trust||Recruiting|
|Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ|
|Contact: Elena Hernan Sanch0 01223369824 email@example.com|
|Contact: Maria King 07792173955 firstname.lastname@example.org|
|Principal Investigator:||Frances Hall Hall, FRCP (UK), D.Phil||Cambridge University Hospitals NHS Foundation Trust|