Abstract
BACKGROUND: Mortality from COVID-19 is high among hospitalized patients and effective therapeutics are lacking. Hypercoagulability, thrombosis and hyperinflammation occur in COVID-19 and may contribute to severe complications. Therapeutic anticoagulation may improve clinical outcomes through anti-thrombotic, anti-inflammatory, and anti-viral mechanisms.
PRIMARY OBJECTIVE: To evaluate whether therapeutic-dose anticoagulation with low molecular weight heparin (LMWH) or unfractionated heparin (UFH) prevents mechanical ventilation and/or death in patients hospitalized with COVID-19 compared to usual care.
STUDY DESIGN: An international, open-label, adaptive randomized controlled trial. Using a Bayesian framework, the trial will declare results as soon as pre-specified posterior probabilities for either superiority, futility, or harm are reached. The trial uses response-adaptive randomization to maximize the probability that patients will receive the more beneficial treatment approach, as treatment effect information accumulates within the trial. By leveraging a common data safety monitoring board and pooling data with a second similar international Bayesian adaptive trial (REMAP-COVID anticoagulation domain), treatment efficacy and safety will be evaluated as efficiently as possible.
PRIMARY OUTCOME: The primary outcome is an ordinal endpoint with three possible outcomes based on the worst status of each patient through day 30: no requirement for invasive mechanical ventilation, invasive mechanical ventilation, or death.
FEASIBILTY AND SIGNIFICANCE: Using an adaptive trial design, the ATTACC trial will establish whether therapeutic anticoagulation can reduce mortality and/or avoid the need for mechanical ventilation in patients hospitalized with COVID-19. Leveraging existing networks to recruit sites will increase enrollment and mitigate enrollment risk in sites with declining COVID-19 cases.
PRIMARY OBJECTIVE: To evaluate whether therapeutic-dose anticoagulation with low molecular weight heparin (LMWH) or unfractionated heparin (UFH) prevents mechanical ventilation and/or death in patients hospitalized with COVID-19 compared to usual care.
STUDY DESIGN: An international, open-label, adaptive randomized controlled trial. Using a Bayesian framework, the trial will declare results as soon as pre-specified posterior probabilities for either superiority, futility, or harm are reached. The trial uses response-adaptive randomization to maximize the probability that patients will receive the more beneficial treatment approach, as treatment effect information accumulates within the trial. By leveraging a common data safety monitoring board and pooling data with a second similar international Bayesian adaptive trial (REMAP-COVID anticoagulation domain), treatment efficacy and safety will be evaluated as efficiently as possible.
PRIMARY OUTCOME: The primary outcome is an ordinal endpoint with three possible outcomes based on the worst status of each patient through day 30: no requirement for invasive mechanical ventilation, invasive mechanical ventilation, or death.
FEASIBILTY AND SIGNIFICANCE: Using an adaptive trial design, the ATTACC trial will establish whether therapeutic anticoagulation can reduce mortality and/or avoid the need for mechanical ventilation in patients hospitalized with COVID-19. Leveraging existing networks to recruit sites will increase enrollment and mitigate enrollment risk in sites with declining COVID-19 cases.
| Original language | English |
|---|---|
| Pages (from-to) | 491-500 |
| Number of pages | 10 |
| Journal | Clinical Trials |
| Volume | 17 |
| Issue number | 5 |
| Early online date | 20 Aug 2020 |
| DOIs | |
| Publication status | Published - 1 Oct 2020 |
Research Groups and Themes
- Covid19
Keywords
- heparin
- thrombosis
- COVID-19
- adaptive clinical trial
- protocol