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

Abstract

Background

Heparin 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.

Methods

Seven 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.

Discussion

The 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 NL8421

ClinicalTrials.gov NCT04061798. Registered on 20 August 2019

EudraCT 2018-003393-27

Trial registration: data set {2b}

Data category	Information
Primary registry and trial identifying number	ClinicalTrials.gov: NCT04061798
Date of registration in primary registry	20-08-2019
Secondary identifying numbers	NTR: NL8421 EudraCT: 2018-003393-27
Source(s) of monetary or material support	ZonMw: The Netherlands Organisation for Health Research and Development Dijklander Ziekenhuis Amsterdam UMC
Primary sponsor	Dijklander Ziekenhuis
Secondary sponsor(s)	N/A
Contact for public queries	A.M. Wiersema, MD, PhD [email protected] 0031-229 208 206
Contact for scientific queries	A.M. Wiersema, MD, PhD [email protected] 0031-229 208 206
Public title	ACT Guided Heparinization During Open Abdominal Aortic Aneurysm Repair (ACTION-1)
Scientific title	ACTION-1: ACT Guided Heparinization During Open Abdominal Aortic Aneurysm Repair, a Randomised Trial
Countries of recruitment	The Netherlands. Soon the recruitment will start in Germany
Health condition(s) or problem(s) studied	Abdominal aortic aneurysm, arterial disease, surgery
Intervention(s)	ACT-guided heparinization 5000 IU of heparin
Key inclusion and exclusion criteria	Ages eligible for the study: ≥18 years Sexes eligible for the study: both Accepts healthy volunteers: no Inclusion criteria:
Study type	Interventional Allocation: randomized Intervention model: parallel assignment Masking: single blind (patient) Primary purpose: treatment Phase IV
Date of first enrolment	March 2020
Target sample size	750
Recruitment status	Recruiting
Primary 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 outcomes	Serious complications as depicted in the Suggested Standards for Reports on Aneurysmal disease: all complications requiring re-operation, longer hospital stay, all complications