AntiThrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC): study design and methodology for an international, adaptive Bayesian randomized controlled trial

B L Houston, P R Lawler, EC Goligher, M E Farkouh, Charlotte A Bradbury, M Carrier, V Dzavik, D Fergusson, R A Fowler, J P Galanaud, P Gross, E G McDonald, M Husain, S R Khan, A Kumar, J. Marshall, S Murthy, A Slutsky, A F Turgeon, S BerryR S Rosenson, G Escobedo, J C Nicolau, R Zarychanski*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

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.

Original languageEnglish
JournalClinical Trials
Publication statusAccepted/In press - 20 Jun 2020

Structured keywords

  • Covid19

Keywords

  • heparin
  • thrombosis
  • COVID-19
  • adaptive clinical trial
  • protocol

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    Houston, B. L., Lawler, P. R., Goligher, EC., Farkouh, M. E., Bradbury, C. A., Carrier, M., Dzavik, V., Fergusson, D., Fowler, R. A., Galanaud, J. P., Gross, P., McDonald, E. G., Husain, M., Khan, S. R., Kumar, A., Marshall, J., Murthy, S., Slutsky, A., Turgeon, A. F., ... Zarychanski, R. (Accepted/In press). AntiThrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC): study design and methodology for an international, adaptive Bayesian randomized controlled trial . Clinical Trials.