ACT Guided Heparinization During Open Abdominal Aortic Aneurysm Repair. (ACTION-1)

February 19, 2024 updated by: Arno Wiersema, Dijklander Ziekenhuis

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

750

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Hamburg, Germany
        • Universitätsklinikum Hamburg-Eppendorf
      • Regensburg, Germany
        • Krankenhaus Barmherzige Brüder
  • Netherlands
      • Almelo, Netherlands
        • Ziekenhuisgroep Twente
      • Groningen, Netherlands
        • Universitair Medisch Centrum Groningen
      • Nieuwegein, Netherlands, 3435 CM
        • St. Antonius Ziekenhuis
    • Drenthe
      • Emmen, Drenthe, Netherlands, 7824AA
        • Treant zorggroep
    • Gelderland
      • Apeldoorn, Gelderland, Netherlands, 7334DZ
        • Gelre Ziekenhuizen
      • Arnhem, Gelderland, Netherlands, 6815 AD
        • Rijnstate
      • Doetinchem, Gelderland, Netherlands, 7009BL
        • Slingeland Ziekenhuis
    • Noord Holland
      • Amsterdam, Noord Holland, Netherlands, 1081 HV
        • AUMC Location VUmc
      • Amsterdam, Noord Holland, Netherlands, 1105AZ
        • AUMC Location AMC
    • Noord-Braband
      • Tilburg, Noord-Braband, Netherlands, 5022 GC
        • Elisabeth TweeSteden Ziekenhuis
    • Noord-Brabant
      • Breda, Noord-Brabant, Netherlands, 4818 CK
        • Amphia
      • Eindhoven, Noord-Brabant, Netherlands, 5623 EJ
        • Catharina Ziekenhuis
    • Noord-Holland
      • Hoorn, Noord-Holland, Netherlands, 1624NP
        • Dijklander ziekenhuis
    • Overijssel
      • Enschede, Overijssel, Netherlands, 7512 KZ
        • Medisch Spectrum Twente
      • Zwolle, Overijssel, Netherlands, 8025 AB
        • Isala
    • Zuid-Holland
      • Den Haag, Zuid-Holland, Netherlands, 2597AX
        • Haaglanden Medisch Centrum
      • Gouda, Zuid-Holland, Netherlands, 2803 HH
        • Groene Hart
      • Leiden, Zuid-Holland, Netherlands, 2333 ZA
        • Leiden Universitair Medisch Centrum
      • Leiderdorp, Zuid-Holland, Netherlands, 2353 GA
        • Alrijne
      • Rotterdam, Zuid-Holland, Netherlands, 3079 DZ
        • Maasstad Ziekenhuis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ACT guided heparinization
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.
Drug: ACT guided heparinization

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.
Active Comparator: 5 000 IU of heparin
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. 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.
Drug: 5 000 IU of heparin

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Combined incidence of all thrombo-embolic complications (TEC) and all-cause mortality.
Time Frame: Within 30 days or during the same admission in hospital
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.
Within 30 days or during the same admission in hospital

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complications (non-TEC).
Time Frame: Within 30 days or during the same admission in hospital
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.
Within 30 days or during the same admission in hospital

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dijklander Ziekenhuis

Collaborators

Amsterdam UMC, location VUmc
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ZonMw: The Netherlands Organisation for Health Research and Development

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2020

Primary Completion (Estimated)

May 1, 2024

Study Completion (Estimated)

November 1, 2024

Study Registration Dates

First Submitted

August 18, 2019

First Submitted That Met QC Criteria

August 18, 2019

First Posted (Actual)

August 20, 2019

Study Record Updates

Last Update Posted (Actual)

February 20, 2024

Last Update Submitted That Met QC Criteria

February 19, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL-66759

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

under pre-defined conditions and contract

IPD Sharing Time Frame

after data lock, 07-2024

IPD Sharing Access Criteria

contract with pre-defined criteria according to government regulation concerning science research

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Surgery

Clinical Trials on ACT guided heparinization

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Peru

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe