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

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 the 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 5000 IU of heparin and no measurements at all. A goal ACT of 200–220 s 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: 5000 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. The goal ACT is 200–220 s. If the ACT after 5 min is < 180 s, 60 IU/kg will be administered; if the ACT is between 180 and 200 s, 30 IU/kg. If the ACT is > 220 s, no extra heparin is given, and the ACT is measured after 30 min and then the same protocol is applied. The expected incidence for the combined endpoint of TEC and mortality is 19% for the 5000 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 5000 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. Registered on 20 August 2019EudraCT 2018-003393-27Trial registration: data set {2b}Data categoryInformationPrimary registry and trial identifying numberClinicalTrials.gov: NCT04061798Date of registration in primary registry20-08-2019Secondary identifying numbersNTR: NL8421EudraCT: 2018-003393-27Source(s) of monetary or material supportZonMw: The Netherlands Organisation for Health Research and DevelopmentDijklander ZiekenhuisAmsterdam UMCPrimary sponsorDijklander ZiekenhuisSecondary sponsor(s)N/AContact for public queriesA.M. Wiersema, MD, PhDArno@wiersema.nu0031-229 208 206Contact for scientific queriesA.M. Wiersema, MD, PhDArno@wiersema.nu0031-229 208 206Public titleACT Guided Heparinization During Open Abdominal Aortic Aneurysm Repair (ACTION-1)Scientific titleACTION-1: ACT Guided Heparinization During Open Abdominal Aortic Aneurysm Repair, a Randomised TrialCountries of recruitmentThe Netherlands. Soon the recruitment will start in GermanyHealth condition(s) or problem(s) studiedAbdominal aortic aneurysm, arterial disease, surgeryIntervention(s)ACT-guided heparinization5000 IU of heparinKey inclusion and exclusion criteriaAges eligible for the study: ≥18 yearsSexes eligible for the study: bothAccepts healthy volunteers: noInclusion criteria:Study typeInterventionalAllocation: randomizedIntervention model: parallel assignmentMasking: single blind (patient)Primary purpose: treatmentPhase IVDate of first enrolmentMarch 2020Target sample size750Recruitment statusRecruitingPrimary outcome(s)The primary efficacy endpoint is 30-day mortality and in-hospital mortality during the same admission.The primary safety endpoint is the incidence of bleeding complications according to E-CABG classification, grade 1 and higher.Key secondary outcomesSerious complications as depicted in the Suggested Standards for Reports on Aneurysmal disease: all complications requiring re-operation, longer hospital stay, all complications