Editor's Choice – Activated Clotting Time Guided Heparinisation during Open Abdominal Aortic Aneurysm Repair (ACTION-1): A Randomised, Multicentre, Single Blind, Superiority Trial

European Journal of Vascular and Endovascular Surgery, vol. 70, pp. 295–305

Abstract

OBJECTIVE: The optimal dosage of intravenous unfractionated heparin and the role of monitoring its effect using activated clotting time (ACT) to prevent thromboembolic complications (TECs) during open abdominal aortic aneurysm (AAA) repair are uncertain. This trial aimed to compare ACT guided heparinisation with a single dose of 5 000 international units (IU) of heparin. METHODS: This was a multicentre, randomised controlled, single blinded, superiority trial (NCT04061798). Patients undergoing elective open AAA repair were randomly assigned (1:1) to receive either ACT guided heparinisation with a dose of 100 IU/kg with a target duration of 200 seconds or a single heparin bolus of 5 000 IU as a control group. The primary efficacy outcome was the combined incidence of TECs and all cause death at 30 days. The safety outcome was the incidence of bleeding complications. ACT measurements were performed using the same device to limit variability. RESULTS: The trial was ended prematurely due to futility after inclusion of 294 patients. After randomisation, 149 patients received ACT guided heparinisation and 145 patients were assigned to the control group. The primary outcome occurred in 34 patients (22.8%) in the ACT group vs. 37 patients (25.5%) in the control group (absolute difference -2.7%, 95% confidence interval [CI] -12.5 - 7.1%). Bleeding complications (absolute difference 9.2%, 95% CI -1.8 - 20.2%) and deaths (absolute difference 7.9%, 95% CI 2.3 - 13.6%) were higher in the ACT group. No difference was found in the incidence of TECs (absolute difference -5.4%, 95% CI -15.0 - 4.2%). CONCLUSION: In patients undergoing open AAA repair, heparinisation with 100 IU/kg and ACT monitoring at a target of 200 seconds did not reduce the primary efficacy outcome and increased the risk of peri-operative bleeding compared with a single bolus of 5 000 IU. Additionally, an increased mortality rate was observed.

Authors 22

1. Vincent Jongkind corresponding

   Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · Dijklander Ziekenhuis · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam

   Affiliation as printed

   Department of Vascular Surgery, Amsterdam University Medical Centres, location Vrije Universiteit, Amsterdam, the Netherlands; Department of Vascular Surgery, Dijklander Hospital, Hoorn, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis and Aortic Disease, Amsterdam, the Netherlands. Electronic address: v.jongkind@amsterdamumc.nl

   Department of Vascular Surgery, Amsterdam University Medical Centers, location Vrije Universiteit, Amsterdam, the Netherlands; Department of Vascular Surgery, Dijklander Hospital, Hoorn, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis and Aortic Disease, Amsterdam, the Netherlands. Electronic address: v.jongkind@amsterdamumc.nl

2. Thomas A H Steunenberg

   Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · Dijklander Ziekenhuis · Vrije Universiteit Amsterdam · University of Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam

   Affiliation as printed

   Department of Vascular Surgery, Amsterdam University Medical Centres, location Vrije Universiteit, Amsterdam, the Netherlands; Department of Vascular Surgery, Dijklander Hospital, Hoorn, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis and Aortic Disease, Amsterdam, the Netherlands; Department of Vascular Surgery, Amsterdam University Medical Centre, location University of Amsterdam, Amsterdam, the Netherlands

   Department of Vascular Surgery, Amsterdam University Medical Centers, location Vrije Universiteit, Amsterdam, the Netherlands; Department of Vascular Surgery, Dijklander Hospital, Hoorn, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis and Aortic Disease, Amsterdam, the Netherlands; Department of Vascular Surgery, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, the Netherlands

3. Liliane C. Roosendaal

   Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · Dijklander Ziekenhuis · Vrije Universiteit Amsterdam · University of Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam

   Affiliation as printed

   Department of Vascular Surgery, Amsterdam University Medical Centres, location Vrije Universiteit, Amsterdam, the Netherlands; Department of Vascular Surgery, Dijklander Hospital, Hoorn, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis and Aortic Disease, Amsterdam, the Netherlands; Department of Vascular Surgery, Amsterdam University Medical Centre, location University of Amsterdam, Amsterdam, the Netherlands

   Department of Vascular Surgery, Amsterdam University Medical Centers, location Vrije Universiteit, Amsterdam, the Netherlands; Department of Vascular Surgery, Dijklander Hospital, Hoorn, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis and Aortic Disease, Amsterdam, the Netherlands; Department of Vascular Surgery, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, the Netherlands

4. Max Hoebink

   Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · Dijklander Ziekenhuis · Vrije Universiteit Amsterdam · University of Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam

   Affiliation as printed

   Department of Vascular Surgery, Amsterdam University Medical Centres, location Vrije Universiteit, Amsterdam, the Netherlands; Department of Vascular Surgery, Dijklander Hospital, Hoorn, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis and Aortic Disease, Amsterdam, the Netherlands; Department of Vascular Surgery, Amsterdam University Medical Centre, location University of Amsterdam, Amsterdam, the Netherlands

   Department of Vascular Surgery, Amsterdam University Medical Centers, location Vrije Universiteit, Amsterdam, the Netherlands; Department of Vascular Surgery, Dijklander Hospital, Hoorn, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis and Aortic Disease, Amsterdam, the Netherlands; Department of Vascular Surgery, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, the Netherlands

5. Jan D. Blankensteijn

   Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam

   Affiliation as printed

   Department of Vascular Surgery, Amsterdam University Medical Centres, location Vrije Universiteit, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis and Aortic Disease, Amsterdam, the Netherlands

   Department of Vascular Surgery, Amsterdam University Medical Centers, location Vrije Universiteit, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis and Aortic Disease, Amsterdam, the Netherlands

6. Mark J.W. Koelemay

   Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam

   Affiliation as printed

   Department of Vascular Surgery, Amsterdam University Medical Centres, location Vrije Universiteit, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis and Aortic Disease, Amsterdam, the Netherlands

   Department of Vascular Surgery, Amsterdam University Medical Centers, location Vrije Universiteit, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis and Aortic Disease, Amsterdam, the Netherlands

7. Rogier H. J. Kropman

   St. Antonius Ziekenhuis

   Affiliation as printed

   Department of Vascular Surgery, St Antonius Hospital, Nieuwegein, the Netherlands

8. Clark J. Zeebregts

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Surgery, Division of Vascular Surgery, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands

9. Jan van Schaik Aachen Department of Vascular Surgery

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Vascular Surgery, Leiden University Medical Centre, Leiden, the Netherlands

10. Jan M.M. Heyligers

    Elisabeth-TweeSteden Ziekenhuis

    Affiliation as printed

    Department of Vascular Surgery, Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands

11. Robert H. Geelkerken

    Medisch Spectrum Twente · University of Twente

    Affiliation as printed

    Department of Vascular Surgery, Medical Spectrum Twente, Enschede, the Netherlands; Multi-Modality Medical Imaging Group, TechMed Centrum, Universiteit Twente, Enschede, the Netherlands

12. M.E. Pierie

    Isala

    Affiliation as printed

    Department of Vascular Surgery, Isala Hospital, Zwolle, the Netherlands

13. Michel M.P.J. Reijnen

    Rijnstate Hospital · University of Twente

    Affiliation as printed

    Multi-Modality Medical Imaging Group, TechMed Centrum, Universiteit Twente, Enschede, the Netherlands; Department of Vascular Surgery, Rijnstate Hospital, Arnhem, the Netherlands; Multi-Modality Medical Imaging Group, University of Twente, Enschede, the Netherlands

14. Susan Lemson

    Slingeland Ziekenhuis

    Affiliation as printed

    Department of Vascular Surgery, Slingeland Hospital, Doetinchem, the Netherlands

15. Rigo Hoencamp Aachen Department of Vascular Surgery

    Alrijne Ziekenhuis

    Affiliation as printed

    Department of Vascular Surgery, Alrijne Hospital, Leiderdorp, the Netherlands

16. Joep A.W. Teijink

    Catharina Ziekenhuis

    Affiliation as printed

    Department of Vascular Surgery, Catharina Hospital, Eindhoven, the Netherlands

17. Markus G. Steinbauer

    Krankenhaus Barmherzige Brüder

    Affiliation as printed

    Department of Vascular Surgery, Barmherzige Brüder Krankenhaus Regensburg, Regensburg, Germany

18. R.J. Hissink

    Treant Zorggroep

    Affiliation as printed

    Department of Vascular Surgery, Treant Zorggroep, Emmen, the Netherlands

19. H.C.J.L. Buscher

    Gelre Hospitals

    Affiliation as printed

    Department of Vascular Surgery, Gelre Hospital, Apeldoorn, the Netherlands

20. Bram Fioole

    Maasstad Ziekenhuis

    Affiliation as printed

    Department of Vascular Surgery, Maasstad Hospital, Rotterdam, the Netherlands

21. Susan van Dieren

    Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam

    Affiliation as printed

    Department of Vascular Surgery, Amsterdam University Medical Centres, location Vrije Universiteit, Amsterdam, the Netherlands

    Department of Vascular Surgery, Amsterdam University Medical Centers, location Vrije Universiteit, Amsterdam, the Netherlands

22. Arno M. Wiersema

    Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · Dijklander Ziekenhuis · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam

    Affiliation as printed

    Department of Vascular Surgery, Amsterdam University Medical Centres, location Vrije Universiteit, Amsterdam, the Netherlands; Department of Vascular Surgery, Dijklander Hospital, Hoorn, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis and Aortic Disease, Amsterdam, the Netherlands

    Department of Vascular Surgery, Amsterdam University Medical Centers, location Vrije Universiteit, Amsterdam, the Netherlands; Department of Vascular Surgery, Dijklander Hospital, Hoorn, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis and Aortic Disease, Amsterdam, the Netherlands