Article ; Online: muLTi-Arm Therapeutic study in pre-ICu patients admitted with Covid-19-Experimental drugs and mechanisms (TACTIC-E): A structured summary of a study protocol for a randomized controlled trial.
2020 Volume 21, Issue 1, Page(s) 690
Abstract: Objectives: To determine if a specific intervention reduces the composite of progression of patients with COVID-19-related disease to organ failure or death as measured by time to incidence of any one of the following: death, invasive mechanical ... ...
Abstract | Objectives: To determine if a specific intervention reduces the composite of progression of patients with COVID-19-related disease to organ failure or death as measured by time to incidence of any one of the following: death, invasive mechanical ventilation, ECMO, cardiovascular organ support (inotropes or balloon pump), or renal failure (estimated Cockcroft Gault creatinine clearance <15ml/min). Trial design: Randomised, parallel arm, open-label, adaptive platform Phase 2/3 trial of potential disease modifying therapies in patients with late stage 1/stage 2 COVID-19-related disease, with a diagnosis based either on a positive assay or high suspicion of COVID-19 infection by clinical, laboratory and radiological assessment. Participants: Patients aged 18 and over, with a clinical picture strongly suggestive of COVID-19-related disease (with/without a positive COVID-19 test) AND a risk count (as defined below) >3 OR ≥3 if risk count includes "Radiographic severity score >3". A risk count is calculated by the following features on admission (1 point for each): radiographic severity score >3, male gender, non-white ethnicity, diabetes, hypertension, neutrophils >8.0 x10 Intervention and comparator: There is increasing evidence of the role of immunomodulation in altering the course of COVID-19. Additionally, various groups have demonstrated the presence of pulmonary shunting in patients with COVID-19 as well as other cardiovascular complications. TACTIC-E will assess the efficacy of the novel immunomodulatory agent EDP1815 versus the approved cardio-pulmonary drugs, Dapagliflozin in combination with Ambrisentan versus the prevailing standard of care. EDP1815 will be given as 2 capsules twice daily (1.6 x 10 Main outcomes: The primary outcome is the incidence (from baseline up to Day 14) to the occurrence of the any one of the following events: death, invasive mechanical ventilation, extra corporeal membrane oxygenation, cardiovascular organ support (inotropes or balloon pump), or renal failure (estimated Cockcroft Gault creatinine clearance <15ml/min). Randomisation: Eligible patients will be randomised using a central web-based randomisation service (Sealed Envelope) in a 1:1:1 ratio, stratified by site to one of the treatment arms or standard of care. Blinding (masking): This is an open-label trial. Data analysis will not be blinded. Numbers to be randomised (sample size): There is no fixed sample size for this study. There will be an early biomarker-based futility analysis performed at a point during the study. If this biomarker futility analysis is not conclusive, then a second futility analysis based on clinical endpoints will be performed after approximately 125 patients have been recruited per arm. Provisionally, further analyses of clinical endpoints will be performed after 229 patients per active arm and later 469 patients per arm have been recruited. Further additional analyses may be triggered by the independent data monitoring committee. Trial status: TACTIC-E Protocol version number 1.0 date May 27 Trial registration: Registered on EU Clinical Trials Register EudraCT Number: 2020-002229-27 registered: 9 June 2020. The trial was also registered on ClinicalTrials.gov (NCT04393246) on 19 May 2020. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. |
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MeSH term(s) | Humans ; Benzhydryl Compounds/administration & dosage ; COVID-19 ; COVID-19 Drug Treatment ; Glucosides/administration & dosage ; Immunologic Factors/therapeutic use ; Intensive Care Units ; Pandemics ; Phenylpropionates/administration & dosage ; Pyridazines/administration & dosage ; Randomized Controlled Trials as Topic ; Respiration, Artificial ; SARS-CoV-2 ; Standard of Care ; Clinical Trials, Phase II as Topic ; Clinical Trials, Phase III as Topic ; Adult |
Chemical Substances | ambrisentan (HW6NV07QEC) ; Benzhydryl Compounds ; dapagliflozin (1ULL0QJ8UC) ; Glucosides ; Immunologic Factors ; Phenylpropionates ; Pyridazines |
Keywords | covid19 |
Language | English |
Publishing date | 2020-07-31 |
Publishing country | England |
Document type | Clinical Trial Protocol ; Letter |
ZDB-ID | 2040523-6 |
ISSN | 1745-6215 ; 1468-6694 ; 1745-6215 |
ISSN (online) | 1745-6215 |
ISSN | 1468-6694 ; 1745-6215 |
DOI | 10.1186/s13063-020-04618-2 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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