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Abdominal Aortic AneurysmPhase 4ACTION-1NCT04061798

ACT Guided Heparinization During Open Abdominal Aortic Aneurysm Repair.

A Phase 4 study testing ACT guided heparinization and 5 000 IU of heparin in people with Abdominal Aortic Aneurysm and Surgery, run by Dijklander Ziekenhuis at 22 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

Aim of the ACTION-1 study is to determine whether ACT guided heparinization decreases thrombo-embolic complications (TEC) and mortality after elective open AAA surgery, without causing more bleeding complications. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ACT guided heparinization and 5 000 IU of heparin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
294 participants
Where
22 sitesin 2 countries
Study dates
2 Mar 2020to 29 Apr 2024
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Able to speak and read in local language of trial hospital.
  • Patients older than 18 years scheduled for elective, open repair of an iliac or abdominal aortic aneurysm distal of the Superior Mesenteric Artery (SMA) (DSAA segment C).
  • Implantation of a tube or bifurcation prosthesis.
  • Trans-abdominal or retroperitoneal surgical approach of aneurysm.
  • Able and willing to provide written informed consent.

Who cannot join

  • Not able to provide written informed consent.
  • Previous open or endovascular intervention on the abdominal aorta (previous surgery on other parts of the aorta or iliac arteries is not an exclusion criterion).
  • History of coagulation disorders, heparin induced thrombocytopenia (HIT), allergy for heparin or thrombocyte pathology.
  • Impaired renal function with EGFR below 30 ml/min.
  • Acute open AAA surgery.
  • Hybrid interventions.
Show all 11Show fewer
  • Connective tissue disorders.
  • Dual anti-platelet therapy, which cannot be discontinued.
  • Life expectancy less than 2 years.
  • Inflammatory, mycotic or infected aneurysms.
  • Allergy for protamine or fish protein

Trial locations and contacts

22 sites in 2 countries.

22 sites in 2 countries

Netherlands20 sites

  • Ziekenhuisgroep Twente

    Almelo

  • AUMC Location VUmc

    Amsterdam, North Holland, 1081 HV

  • AUMC Location AMC

    Amsterdam, North Holland, 1105AZ

  • Gelre Ziekenhuizen

    Apeldoorn, Gelderland, 7334DZ

  • Rijnstate

    Arnhem, Gelderland, 6815 AD

  • Amphia

    Breda, North Brabant, 4818 CK

  • Slingeland Ziekenhuis

    Doetinchem, Gelderland, 7009BL

  • Catharina Ziekenhuis

    Eindhoven, North Brabant, 5623 EJ

  • Treant Zorggroep

    Emmen, Drenthe, 7824AA

  • Medisch Spectrum Twente

    Enschede, Overijssel, 7512 KZ

  • Groene Hart

    Gouda, South Holland, 2803 HH

  • Universitair Medisch Centrum Groningen

    Groningen

  • Dijklander Ziekenhuis

    Hoorn, North Holland, 1624NP

  • Leiden Universitair Medisch Centrum

    Leiden, South Holland, 2333 ZA

  • Alrijne

    Leiderdorp, South Holland, 2353 GA

  • St. Antonius ziekenhuis

    Nieuwegein, 3435 CM

  • Maasstad Ziekenhuis

    Rotterdam, South Holland, 3079 DZ

  • Haaglanden Medisch Centrum

    The Hague, South Holland, 2597AX

  • Elisabeth TweeSteden Ziekenhuis

    Tilburg, Noord-Braband, 5022 GC

  • Isala

    Zwolle, Overijssel, 8025 AB

Other trials in Netherlands

Germany2 sites

  • Universitätsklinikum Hamburg-Eppendorf

    Hamburg

  • Krankenhaus Barmherzige Brüder

    Regensburg

Other trials in Germany

About this study

Official title: ACTION-1: ACT Guided Heparinization During Open Abdominal Aortic Aneurysm Repair, a Randomised Trial.

Aim of the ACTION-1 study is to determine whether ACT guided heparinization decreases thrombo-embolic complications (TEC) and mortality after elective open AAA surgery, without causing more bleeding complications.

Read the detailed description

Heparin is used during open abdominal aortic aneurysm (AAA) surgery to reduce thrombo-embolic complications (TEC): such as myocardial infarction, stroke, peripheral embolic events and the related mortality. On the other hand, heparin may increase blood loss, causing harm for the patient.

Heparin has an unpredictable effect in the individual patient. The effect of heparin can be measured by using the Activated Clotting Time (ACT). ACT measurement in open AAA repair could be introduced to ensure the individual patient of safe, tailor-made anticoagulation with a goal ACT of 200-220 seconds. A randomized controlled trial (RCT) has to prove that ACT guided heparinization would result in fewer TEC and lower mortality than a standardized bolus of heparin of 5 000 international units (IU), the current gold standard. ACT guided heparinization results in higher doses of heparin during operation and this should not result in significantly more bleeding complications of importance.

The ACTION-1 study will evaluate the effect of weight dosed heparinization during open abdominal aortic aneurysm surgery.The study will be an international multi-centre single blind randomized controlled trial. Patients will be randomized using a computerized program (CASTOR EDC) with a random block size of a maximum of 8. The randomization will be stratified by participating centre. Separate evaluation of results and if complications can be labelled as TEC, will be performed by an Independent Central Adjudication Committee. The 3 members of this Committee will be blinded with regard to if the patient was randomized for ACT guided heparinization or standard bolus of 5 000 IU without ACT measurements.

In the intervention group, heparin is given to reach an ACT of 200-220 seconds. Based on the ACT, an additional dose of heparin will be administered. Five minutes after every administration of heparin the ACT is measured. If the ACT is 200 seconds or longer, the next ACT measurement is performed every 30 minutes, until the end of the procedure or until new heparin administration is required (because of ACT < 200 seconds). Depending on the ACT value near the end of surgery, protamine will be given to neutralize the effect of heparin.

In the comparative group, a single dose of 5 000 IU of heparin will be given 3-5 minutes before clamping of the aorta. No ACT measurements will be performed, except for one ACT measurement after re-establishing blood flow and removing all clamps. Depending on that ACT value near the end of surgery, the local protamine can be given to neutralize the effect of heparin.

Being tested
ACT guided heparinization, 5 000 IU of heparin
Keywords
ACT guided heparinization in open aortic surgery
Medical subject headings
Aortic Aneurysm, Abdominal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ACT guided heparinizationDrug

    If the ACT is <180 sec., an additional dose of heparin of 60 IU/kg is administered. If the ACT is 180-200 sec., 30 IU/kg.

    If the ACT is >200 sec., no extra heparin is given. 5 min. after every administration of heparin the ACT is measured. If the ACT is >200 sec, the next ACT measurement is performed every 30 min., until the end of the procedure or until new heparin administration is required. After each new dose of heparin, an ACT measurement is performed after 5 min. and the above- described protocol of ACT measurements will be repeated. After re-establishing blood flow and removing all clamps, the ACT is measured.

    If the ACT at closure is 200-250 sec., 2500 IU of protamine should be administered. If >250 sec., 5000 IU protamine. If 180-200 sec., 1000 IU protamine. 5 min. after the administration of protamine, the ACT is measured. The ACT should preferably be below 180 sec. If the ACT is still more than 200 sec., protamine should be administered again.

  • 5 000 IU of heparinDrug

    A single dose of 5 000 IU of heparin is given 3-5 min before clamping of the aorta. No ACT measurements are performed, except for one ACT measurement after re-establishing blood flow and removing all clamps. Only on clarified indications extra doses of heparin or protamine are permitted, at the discretion of the attending vascular surgeon. Indications could be clot formation intravascular or in a prosthesis, excessive bleeding or prolonged operation duration. Deviations from protocol should be clearly stated with reasoning in the operative report.

    If the ACT at closure is between 200 and 250 s, 2500 IU protamine should be administered. If the ACT is higher than 250 s, 5000 IU protamine should be administered. If the ACT is between 180 and 200 s, 1000 IU protamine should be administered. Five minutes after the administration of protamine, the ACT is measured. The ACT should preferably be below 180 s. If the ACT is still more than 200 s, protamine should be administered again.

Study groups in NCT04061798
Study groupRoleWhat they receive
ACT guided heparinizationExperimentalHeparin is given to reach an ACT of 200-220 seconds. At the start of the procedure, before any heparin is given, a baseline ACT measurement is performed. 3-5 minutes before clamping of the aorta 100 IU/kg bodyweight of heparin is administrated intravenously. 5 minutes after administration of heparin, ACT measurement is performed.
Receives: Drug: ACT guided heparinization
5 000 IU of heparinActive comparatorA single dose of 5 000 IU of heparin is given 3-5 minutes before clamping of the aorta. No ACT measurements are performed, except for one ACT measurement after re-establishing blood flow and removing all clamps. Depending on that ACT value near the end of surgery, the local protamine can be given to neutralize the effect of heparin. Only on clarified indications extra doses of heparin or protamine are permitted, at the discretion of the attending vascular surgeon. Indications could be clot formation intravascular or in a prosthesis, excessive bleeding or prolonged operation duration. Deviations from protocol should be clearly stated with reasoning in the operative report.
Receives: Drug: 5 000 IU of heparin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Combined incidence of all thrombo-embolic complications (TEC) and all-cause mortality.

    TEC are any complication as caused by thrombus or embolus perioperatively, including but not exclusively: myocardial infarction, leg ischemia, deep venous thrombosis, colon ischemia, transient ischemic attack (TIA)/stroke, graft thrombosis, peroperative thrombus requiring embolectomy or redo of an anastomosis, thrombus or embolus in organs or lower limbs and other peripheral thrombosis. Incidence of bleeding complications according to European multicenter study on Coronary Artery Bypass Grafting (E-CABG) classification, grade 1 and higher: per- or postoperative transfusion of 2 or more units of red blood cells, transfusion of platelets, transfusion of fresh frozen plasma or reoperation for bleeding during hospital stay.

    Measured: Within 30 days or during the same admission in hospital

Secondary outcomes (1)

  1. Complications (non-TEC).

    All complications requiring re-operation, longer hospital stay, all other complications. Incidence of kidney injury as defined by RIFLE criteria: rise of serum creatinine > 100% or decrease of estimated Glomerular Filtration Rate (eGFR) with 50%.32 Allergic reactions. ACT values (in intervention group), total heparin administration, protamine administration. Peroperative blood loss, blood transfusions either autologous or homologous, other blood products administration, total operative time, aortic clamping time, use of adjunctive haemostatic products, length of hospital (including ICU) stay. Health status as measured with the EQ-5D-5L. Economic and healthcare costs evaluation by the institute for Medical Technology Assessment (iMTA) Medical Consumption Questionnaire(IMCQ) and iMTA Productivity Cost Questionnaire (IPCQ) and addition of out-of-pocket expenses.

    Measured: Within 30 days or during the same admission in hospital

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Aug 2019
  2. Study start2 Mar 2020
  3. Primary completion13 Apr 2024
  4. Study completion29 Apr 2024

Why it stopped: Futility

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Intervention group: Heparin is given to reach an ACT of 200-220 seconds. At the start of the procedure, before any heparin is given, a baseline ACT measurement is performed. 3-5 minutes before clamping of the aorta 100 IU/kg bodyweight of heparin is administrated intravenously. 5 minutes after administration of heparin, ACT measurement is performed. Comparative group: A single dose of 5 000 IU of heparin is given 3-5 minutes before clamping of the aorta. No ACT measurements are performed, except for one ACT measurement after re-establishing blood flow and removing all clamps.
Masking
Single blind
Who is masked
Participant
Enrolment
294 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04061798
Sponsor's protocol ID
NL-66759
Acronym
ACTION-1
Status last verified
Feb 2025
First submitted
18 Aug 2019
Last updated
6 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: under pre-defined conditions and contract

Publications

  • Burgers LT, Vahl AC, Severens JL, Wiersema AM, Cuypers PW, Verhagen HJ, Redekop WK. Cost-effectiveness of Elective Endovascular Aneurysm Repair Versus Open Surgical Repair of Abdominal Aortic Aneurysms. Eur J Vasc Endovasc Surg. 2016 Jul;52(1):29-40. doi: 10.1016/j.ejvs.2016.03.001. Epub 2016 Apr 23.

    PubMed 27118618

  • Behrendt CA, Sedrakyan A, Riess HC, Heidemann F, Kolbel T, Petersen J, Debus ES. Short-term and long-term results of endovascular and open repair of abdominal aortic aneurysms in Germany. J Vasc Surg. 2017 Dec;66(6):1704-1711.e3. doi: 10.1016/j.jvs.2017.04.040. Epub 2017 Aug 7.

    PubMed 28780975

  • Behrendt CA, Riess HC, Schwaneberg T, Larena-Avellaneda A, Kolbel T, Tsilimparis N, Spanos K, Debus ES, Sedrakyan A. Incidence, Predictors, and Outcomes of Colonic Ischaemia in Abdominal Aortic Aneurysm Repair. Eur J Vasc Endovasc Surg. 2018 Oct;56(4):507-513. doi: 10.1016/j.ejvs.2018.06.010. Epub 2018 Jul 20.

    PubMed 30037737

  • Deery SE, O'Donnell TFX, Bodewes TCF, Dalebout BA, Pothof AB, Shean KE, Darling JD, Schermerhorn ML. Early reintervention after open and endovascular abdominal aortic aneurysm repair is associated with high mortality. J Vasc Surg. 2018 Feb;67(2):433-440.e1. doi: 10.1016/j.jvs.2017.06.104. Epub 2017 Sep 21.

    PubMed 28943011

  • Trenner M, Haller B, Storck M, Reutersberg B, Kallmayer MA, Eckstein HH. Trends in Patient Safety of Intact Abdominal Aortic Aneurysm Repair: German Registry Data on 36,594 Procedures. Eur J Vasc Endovasc Surg. 2017 May;53(5):641-647. doi: 10.1016/j.ejvs.2016.12.024. Epub 2017 Jan 19.

    PubMed 28110907

  • Hynes CF, Endicott KM, Iranmanesh S, Amdur RL, Macsata R. Reoperation rates after open and endovascular abdominal aortic aneurysm repairs. J Vasc Surg. 2017 May;65(5):1323-1328. doi: 10.1016/j.jvs.2016.09.053. Epub 2017 Jan 7.

    PubMed 28073669

  • Prinssen M, Verhoeven EL, Buth J, Cuypers PW, van Sambeek MR, Balm R, Buskens E, Grobbee DE, Blankensteijn JD; Dutch Randomized Endovascular Aneurysm Management (DREAM)Trial Group. A randomized trial comparing conventional and endovascular repair of abdominal aortic aneurysms. N Engl J Med. 2004 Oct 14;351(16):1607-18. doi: 10.1056/NEJMoa042002.

    PubMed 15483279

  • Lo RC, Bensley RP, Hamdan AD, Wyers M, Adams JE, Schermerhorn ML; Vascular Study Group of New England. Gender differences in abdominal aortic aneurysm presentation, repair, and mortality in the Vascular Study Group of New England. J Vasc Surg. 2013 May;57(5):1261-8, 1268.e1-5. doi: 10.1016/j.jvs.2012.11.039. Epub 2013 Feb 4.

    PubMed 23384493

  • Wiersema A, Bruijninckx C, Reijnen M, Vos J, Van Delden O, Vahl A, Zeebregts C, Moll F. Perioperative prophylactic antithrombotic strategies in vascular surgery: current practice in the Netherlands. J Cardiovasc Surg (Torino). 2015 Feb;56(1):119-25. Epub 2013 Jan 22.

    PubMed 23337406

  • Wiersema AM, Jongkind V, Bruijninckx CM, Reijnen MM, Vos JA, van Delden OM, Zeebregts CJ, Moll FL; CAPPAStudy Group Consensus on Arterial PeriProcedural Anticoagulation. Prophylactic perioperative anti-thrombotics in open and endovascular abdominal aortic aneurysm (AAA) surgery: a systematic review. Eur J Vasc Endovasc Surg. 2012 Oct;44(4):359-67. doi: 10.1016/j.ejvs.2012.06.008. Epub 2012 Jul 24.

    PubMed 22831869

  • Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):188S-203S. doi: 10.1378/chest.126.3_suppl.188S.

    PubMed 15383472

  • Finley A, Greenberg C. Review article: heparin sensitivity and resistance: management during cardiopulmonary bypass. Anesth Analg. 2013 Jun;116(6):1210-22. doi: 10.1213/ANE.0b013e31827e4e62. Epub 2013 Feb 13.

    PubMed 23408671

  • Arsenault KA, Paikin JS, Hirsh J, Dale B, Whitlock RP, Teoh K, Young E, Ginsberg JS, Weitz JI, Eikelboom JW. Subtle differences in commercial heparins can have serious consequences for cardiopulmonary bypass patients: A randomized controlled trial. J Thorac Cardiovasc Surg. 2012 Oct;144(4):944-950.e3. doi: 10.1016/j.jtcvs.2012.05.065. Epub 2012 Jun 27.

    PubMed 22743176

  • Nath FC, Muller DW, Rosenschein U, Ellis SG, Topol EJ. Heparin monitoring during coronary intervention: activated clotting time versus activated partial thromboplastin time. Can J Cardiol. 1993 Nov;9(9):797-801.

    PubMed 8281479

  • Chew DP, Bhatt DL, Lincoff AM, Moliterno DJ, Brener SJ, Wolski KE, Topol EJ. Defining the optimal activated clotting time during percutaneous coronary intervention: aggregate results from 6 randomized, controlled trials. Circulation. 2001 Feb 20;103(7):961-6. doi: 10.1161/01.cir.103.7.961.

    PubMed 11181470

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing ACT guided heparinization and 5 000 IU of heparin in people with Abdominal Aortic Aneurysm and Surgery, run by Dijklander Ziekenhuis at 22 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Netherlands, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Futility). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Combined incidence of all thrombo-embolic complications (TEC) and all-cause mortality. (time frame: Within 30 days or during the same admission in hospital). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04061798, which also lists 33 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2025.

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