Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC)
Status:
Completed
Trial end date:
2021-05-17
Target enrollment:
Participant gender:
Summary
Endothelial injury as a consequence of SARS-CoV-2 infection leads to a dysregulated host
inflammatory response and activation of coagulation pathways. Macro- and micro-vascular
thrombosis may contribute to morbidity, organ failure, and death. Therapeutic anticoagulation
with heparin may improve clinical outcomes in patients with COVID-19 through anti-thrombotic,
anti-inflammatory, and anti-viral activities of heparins. This pragmatic, Bayesian adaptive
randomized controlled trial will determine whether therapeutic anticoagulation with heparin
(subcutaneous low molecular weight heparin or intravenous unfractionated heparin) versus
usual care reduces the need for intubation or death in hospitalized patients with COVID-19.
The trial uses an adaptive design which was chosen to overcome limitations in available data
to inform a priori estimation of event rates and possible effect sizes. The adaptive design
also includes response-adaptive randomization based on baseline D-dimer level, probing for
differential efficacy across subgroups defined based on initial D-dimer level. This Bayesian
adaptive randomized trial will stop at a conclusion 1) when the posterior probability that
the proportional odds ratio is greater than 1.0 reaches 99% (definition of benefit); 2) when
the posterior probability that the proportional odds ratio is greater than 1.2 is less than
10% (definition of futility) or; 3) when the posterior probability that the proportional odds
ratio is less than 1.0 is greater than 90% (definition of harm). The trial will enroll a
maximum of 3,000 patients, although in many simulations the trial may require fewer patients.
The trial is strategically aligned with the international REMAP-CAP/COVID platform trial to
accelerate evidence generation.
Phase:
Phase 2/Phase 3
Details
Lead Sponsor:
University of Manitoba
Collaborators:
Hamilton Health Sciences Corporation Hopital Montfort University Health Network, Toronto