ACTION-1: study protocol for a randomised controlled trial on ACT guided heparinization during open abdominal aortic aneurysm repair {1}

Abstract

BackgroundHeparin is used worldwide for 70 years during all non-cardiac arterial procedures (NCAP) to reduce thrombo-embolic complications (TEC). But heparin also increases blood loss causing possible harm for the patient. Heparin has an unpredictable effect in the individual patient. The Activated Clotting Time (ACT) can measure the effect of heparin. Currently this ACT is not measured during NCAP as standard of care, contrary to during cardiac interventions, open and endovascular. A RCT will evaluate if ACT guided heparinization results in less TEC than the current standard: a single bolus of 5 000 IU of heparin and no measurements at all. A goal ACT of 200-220 seconds should be reached during ACT guided heparinization and this should decrease (mortality caused by) TEC, while not increasing major bleeding complications. This RCT will be executed during open abdominal aortic aneurysm (AAA) surgery, as this is a standardized procedure throughout Europe.MethodsSeven-hundred-fifty patients, who will undergo open AAA repair of an aneurysm originating below the superior mesenteric artery, will be randomised in 2 treatment arms: 5 000 IU of heparin and no ACT measurements and no additional doses of heparin, or a protocol of 100 IU/kg bolus of heparin and ACT measurements after 5 min., and then every 30 min. Goal ACT is 200-220 sec. If the ACT after 5 min. is < 180 sec. 60 IU/kg will be administered, if the ACT is between 180 and 200 sec. 30 IU/kg. If the ACT is > 220 sec. no extra heparin is given, and the ACT is measured after 30 minutes and then the same protocol is applied. The expected incidence for the combined endpoint of TEC and mortality is 19% for the 5 000 IU group and 11% for the ACT guided group.DiscussionThe ACTION-1 trial is an international RCT during open AAA surgery, designed to show superiority of ACT guided heparinization compared to the current standard of a single bolus of 5 000 IU of heparin. A significant reduction in TEC and mortality, without more major bleeding complications, must be proven with a relevant economic benefit.Trial registration {2a}NTR: NL8421Clinicaltrials.gov: NCT04061798. Date of registration: 20-08-2019. https://clinicaltrials.gov/ct2/show/NCT04061798?cond=NCT04061798&draw=2&rank=1 EudraCT: 2018-003393-27