Arterial DiseaseMANCONCT03426293
Measuring the ACT During Non-cardiac Arterial Procedures.
An observational study of Arterial Disease and Surgery, run by Dijklander Ziekenhuis at 3 sites in Netherlands.
Trial summary
Aim of the MANCO study is to establish for once and for all that monitoring the effect of heparin during NCVI (Non-Cardiac Vascular Interventions) is essential to ensure the individual patient of safe and tailor-made anticoagulation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arterial Disease, Surgery, PTA
- What is being tested?
- Measuring the ACT to determine effect of heparin
- How many people
- 1,000 participants
- Where
- 3 sitesNetherlands
- Study dates
- 21 Dec 2016to 31 Jan 2024
- How long will I take part?
- 12 Months
- Phase
- Observational
- 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
Study population: - All patients in participating centers undergoing NCVI, older than 18 years
Who may be able to join
- All patients in participating centers undergoing Non-Cardiac Vascular (arterial) Intervention open or endovascular, older than 18 years
Who cannot join
- Patients with a known history of coagulation disorders or a EGFR lower than 30 ml/min.
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites
Vrije Universiteit Medisch Centrum
Amsterdam, North Holland, 1081HV
Westfriesgasthuis
Hoorn, North Holland, 1624NP
Isala klinieken
Zwolle, 8025 AB
About this study
Official title: MANCO: Measuring the ACT During Non-cardiac Arterial Procedures.
Aim of the MANCO study is to establish for once and for all that monitoring the effect of heparin during NCVI (Non-Cardiac Vascular Interventions) is essential to ensure the individual patient of safe and tailor-made anticoagulation. Not measuring the effect of the administered heparin exposes the patient to unnecessary risks of thrombo-embolic and bleeding complications. First aim of the MANCO study is to prove that the standardized bolus of 5000 IU of heparin, used by 90% of vascular specialists in Europe, results in inadequate anticoagulation in more than 80% of patients. These measurements will be performed using the Hemostasis Management System by Medtronic.
Read the detailed description
Heparin is used worldwide by all vascular surgeons and interventional radiologists (IR) during non-cardiac vascular interventions (NCVI), both open and endovascular. Heparin is used to reduce or prevent arterial thrombo-embolic complications (ATEC). Heparin reduces the clotting of blood and thereby coagulation. This also explains the negative side-effect of using heparin: its use can lead to bleeding-complications, possibly causing the need for blood tranfusions, more hematomas necessitating re-interventions and increasing the risk of infections.
Since the 1970's it is well known that heparin has a non-linear dose response curve and also a non-linear elimination curve in the individual patient.
Despite this fact, more than 95% of all vascular surgeons and IR use a standardized bolus of 5000 IU in every patient. Multiple studies have demonstrated that up to 70% of patients is not adequately anticoagulated during NCVI using that bolus of 5000 IU.
During open or endovascular cardiac interventions the effect of heparin is always routinely measured using the activated clotting time (ACT).
Despite this knowledge the percentage of vascular surgeons and/or IR that measure the effect of heparin during NCVI routinely is astonishing low: 0-5%, in the US this percentage is probably higher (30%), possibly due to medico-legal reasons. Existing guidelines on NCVI depict different regimes on the use of heparin or do not mention this use at all.
The Hemostasis Management System (HMS, Medtronic) measures the ACT, but it also calculates a heparin dose response curve in the individual patient. This curve supplies the vascular surgeon or IR a tool to administer the exact amount of heparin needed to reach a desired ACT. Also the exact dose of protamine can be calculated to neutralize the effect of remaining circulating heparin in the individual patient. The use of the HMS in cardiac vascular procedures has to led to a reduced need for blood transfusions, less postoperative bleeding complications and a reduction of peri-procedural myocardial infarctions and other ATEC.
To determine if the HMS can be of equal high value during NCVI, a pilot study was performed at the VUMC, called Hepvasc. Results of this pilot (submitted) and other sparse results from literature, show that HMS can be used during NCVI. Furthermore, results indicated that the bolus of 5000 IU resulted in inadequate anticoagulation in 7 out of 18 included patients. This exposes those patients to a higher risk of ATEC.
As a result of this pilot, the MANCO study is designed with the HMS during NCVI. The MANCO study will evaluate the data of heparin management with the HMS in number of large vascular centers, starting in the Netherlands and after that in Europe. Measurements with the HMS will be used for the evaluation of the local heparin protocol by the individual vascular surgeon or IR. The MANCO study will be started permitting every center to apply their current heparin protocol. This includes the dosage of heparin and possible extra dosing of heparin to reach a desired ACT. The MANCO study is started as a prospective data registry and observational study of the ACT with an extensive case record form (CRF). Regular blood samples for ACT measurements will be done, so no extra invasive measurements are performed in the patient. Data will be collected according to all legal requirements and permission of local medical ethics committees is granted.
- Conditions
- Arterial Disease, Surgery, PTA, Peripheral Arterial Disease
- Being tested
- Measuring the ACT to determine effect of heparin
- Keywords
- heparin;ACT;non-cardiac vascular;peri-procedural
- Medical subject headings
- Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Measuring the ACT to determine effect of heparinOther
Measuring the ACT to determine effect of heparin during non-cardiac arterial procedures
| Study group | Role | What they receive |
|---|---|---|
| Arterial procedure and ACT measurement | All patients undergoing an open or endovascular arterial procedure in which heparin is used peri-procedurally and the ACT is measured to determine effect of heparin Receives: Other: Measuring the ACT to determine effect of heparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of Activated Clotting Time
Change of Activated Clotting Time, before and after administration of heparin
Measured: ACT measured before heparin, 5 minutes after and than at 30 minutes intervals. After a repeated dose of heparin again after 5 minutes and 30 minutes intervals
Secondary outcomes (1)
Complications
All complications as depicted in Suggested Standards for reports on arterial procedures and local complication registration. Vascular and non-vascular
Measured: 30 days or same admission, 6 weeks, 6 months and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2018
- Study start21 Dec 2016
- Primary completion31 Jan 2024
- Study completion31 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Arterial DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (actual)
- Target duration
- 12 Months
Sponsor and investigators
- Lead sponsor
- Dijklander Ziekenhuis
- Sponsor type
- University, hospital or other
- Collaborators
- Medtronic
- Responsible party
- Principal investigator, Arno Wiersema, Dijklander Ziekenhuis
- Investigators
- Arno M Wiersema, MD, PhD, Principal investigator, Dijklander Ziekenhuis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03426293
- Sponsor's protocol ID
- M016-045
- Acronym
- MANCO
- Status last verified
- Feb 2025
- First submitted
- 27 Jan 2018
- Last updated
- 6 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All ACT values can be obtained after trial with PI
Publications
Wiersema AM, Watts C, Durran AC, Reijnen MM, van Delden OM, Moll FL, Vos JA. The Use of Heparin during Endovascular Peripheral Arterial Interventions: A Synopsis. Scientifica (Cairo). 2016;2016:1456298. doi: 10.1155/2016/1456298. Epub 2016 Apr 17.
PubMed 27190678Wiersema A, Jongkind V, Bruijninckx C, Reijnen M, Vos J, Van Delden O, Zeebregts C, Moll F. Prophylactic intraoperative antithrombotics in open infrainguinal arterial bypass surgery: a systematic review. J Cardiovasc Surg (Torino). 2015 Feb;56(1):127-43. Epub 2014 Mar 4.
PubMed 24594802Wiersema AM, Vos JA, Bruijninckx CMA, van Delden OM, Reijnen MMPJ, Vahl A, Zeebregts CJ, Moll FL. Periprocedural prophylactic antithrombotic strategies in interventional radiology: current practice in the Netherlands and comparison with the United kingdom. Cardiovasc Intervent Radiol. 2013 Dec;36(6):1477-1492. doi: 10.1007/s00270-013-0558-6. Epub 2013 Feb 13.
PubMed 23404518Wiersema 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 22831869Finley 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 23408671Mabry CD, Thompson BW, Read RC. Activated clotting time (ACT) monitoring of intraoperative heparinization in peripheral vascular surgery. Am J Surg. 1979 Dec;138(6):894-900. doi: 10.1016/0002-9610(79)90318-0.
PubMed 507308Goldhammer JE, Zimmerman D. Pro: Activated Clotting Time Should Be Monitored During Heparinization For Vascular Surgery. J Cardiothorac Vasc Anesth. 2018 Jun;32(3):1494-1496. doi: 10.1053/j.jvca.2017.04.047. Epub 2017 Apr 26. No abstract available.
PubMed 28943189Veerhoek D, Groepenhoff F, van der Sluijs MGJM, de Wever JWB, Blankensteijn JD, Vonk ABA, Boer C, Vermeulen CFW. Individual Differences in Heparin Sensitivity and Their Effect on Heparin Anticoagulation During Arterial Vascular Surgery. Eur J Vasc Endovasc Surg. 2017 Oct;54(4):534-541. doi: 10.1016/j.ejvs.2017.07.006. Epub 2017 Aug 9.
PubMed 28802634
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MANCO: Measuring the ACT During Non-cardiac Arterial Procedures.
- ClinicalTrials.gov ID
- NCT03426293
- Acronym / sponsor ID
- MANCO / M016-045
- Conditions
- Arterial Disease, Surgery, PTA, Peripheral Arterial Disease
- Keywords
- heparin;ACT;non-cardiac vascular;peri-procedural
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,000 participants (actual)
- Lead sponsor
- Dijklander ZiekenhuisUniversity, hospital or other
- Collaborators
- Medtronic
- Study start
- 21 Dec 2016 (actual)
- Primary completion
- 31 Jan 2024 (actual)
- Study completion
- 31 Jan 2024 (actual)
- First posted
- 8 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Aim of the MANCO study is to establish for once and for all that monitoring the effect of heparin during NCVI (Non-Cardiac Vascular Interventions) is essential to ensure the individual patient of safe and tailor-made anticoagulation. Not measuring the effect of the administered heparin exposes the patient to unnecessary risks of thrombo-embolic and bleeding complications. First aim of the MANCO study is to prove that the standardized bolus of 5000 IU of heparin, used by 90% of vascular specialists in Europe, results in inadequate anticoagulation in more than 80% of patients. These measurements will be performed using the Hemostasis Management System by Medtronic.
Detailed description
Heparin is used worldwide by all vascular surgeons and interventional radiologists (IR) during non-cardiac vascular interventions (NCVI), both open and endovascular. Heparin is used to reduce or prevent arterial thrombo-embolic complications (ATEC). Heparin reduces the clotting of blood and thereby coagulation. This also explains the negative side-effect of using heparin: its use can lead to bleeding-complications, possibly causing the need for blood tranfusions, more hematomas necessitating re-interventions and increasing the risk of infections.
Since the 1970's it is well known that heparin has a non-linear dose response curve and also a non-linear elimination curve in the individual patient.
Despite this fact, more than 95% of all vascular surgeons and IR use a standardized bolus of 5000 IU in every patient. Multiple studies have demonstrated that up to 70% of patients is not adequately anticoagulated during NCVI using that bolus of 5000 IU.
During open or endovascular cardiac interventions the effect of heparin is always routinely measured using the activated clotting time (ACT).
Despite this knowledge the percentage of vascular surgeons and/or IR that measure the effect of heparin during NCVI routinely is astonishing low: 0-5%, in the US this percentage is probably higher (30%), possibly due to medico-legal reasons. Existing guidelines on NCVI depict different regimes on the use of heparin or do not mention this use at all.
The Hemostasis Management System (HMS, Medtronic) measures the ACT, but it also calculates a heparin dose response curve in the individual patient. This curve supplies the vascular surgeon or IR a tool to administer the exact amount of heparin needed to reach a desired ACT. Also the exact dose of protamine can be calculated to neutralize the effect of remaining circulating heparin in the individual patient. The use of the HMS in cardiac vascular procedures has to led to a reduced need for blood transfusions, less postoperative bleeding complications and a reduction of peri-procedural myocardial infarctions and other ATEC.
To determine if the HMS can be of equal high value during NCVI, a pilot study was performed at the VUMC, called Hepvasc. Results of this pilot (submitted) and other sparse results from literature, show that HMS can be used during NCVI. Furthermore, results indicated that the bolus of 5000 IU resulted in inadequate anticoagulation in 7 out of 18 included patients. This exposes those patients to a higher risk of ATEC.
As a result of this pilot, the MANCO study is designed with the HMS during NCVI. The MANCO study will evaluate the data of heparin management with the HMS in number of large vascular centers, starting in the Netherlands and after that in Europe. Measurements with the HMS will be used for the evaluation of the local heparin protocol by the individual vascular surgeon or IR. The MANCO study will be started permitting every center to apply their current heparin protocol. This includes the dosage of heparin and possible extra dosing of heparin to reach a desired ACT. The MANCO study is started as a prospective data registry and observational study of the ACT with an extensive case record form (CRF). Regular blood samples for ACT measurements will be done, so no extra invasive measurements are performed in the patient. Data will be collected according to all legal requirements and permission of local medical ethics committees is granted.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 12 Months
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arterial procedure and ACT measurement | – | Other: Measuring the ACT to determine effect of heparinAll patients undergoing an open or endovascular arterial procedure in which heparin is used peri-procedurally and the ACT is measured to determine effect of heparin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- - All patients in participating centers undergoing NCVI, older than 18 years
Key inclusion criteria (1 listed)
- All patients in participating centers undergoing Non-Cardiac Vascular (arterial) Intervention open or endovascular, older than 18 years
Key exclusion criteria (1 listed)
- Patients with a known history of coagulation disorders or a EGFR lower than 30 ml/min.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Measuring the ACT to determine effect of heparinMeasuring the ACT to determine effect of heparin during non-cardiac arterial procedures | Other | Arterial procedure and ACT measurement |
Primary outcome
Change of Activated Clotting Time
Time frame: ACT measured before heparin, 5 minutes after and than at 30 minutes intervals. After a repeated dose of heparin again after 5 minutes and 30 minutes intervals
Change of Activated Clotting Time, before and after administration of heparin
1 secondary outcome
Complications
Time frame: 30 days or same admission, 6 weeks, 6 months and 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2025.
- Background: PubMed 27190678Wiersema AM, Watts C, Durran AC, Reijnen MM, van Delden OM, Moll FL, Vos JA. The Use of Heparin during Endovascular Peripheral Arterial Interventions: A Synopsis. Scientifica (Cairo). 2016;2016:1456298. doi: 10.1155/2016/1456298. Epub 2016 Apr 17.
- Background: PubMed 24594802Wiersema A, Jongkind V, Bruijninckx C, Reijnen M, Vos J, Van Delden O, Zeebregts C, Moll F. Prophylactic intraoperative antithrombotics in open infrainguinal arterial bypass surgery: a systematic review. J Cardiovasc Surg (Torino). 2015 Feb;56(1):127-43. Epub 2014 Mar 4.
- Background: PubMed 23404518Wiersema AM, Vos JA, Bruijninckx CMA, van Delden OM, Reijnen MMPJ, Vahl A, Zeebregts CJ, Moll FL. Periprocedural prophylactic antithrombotic strategies in interventional radiology: current practice in the Netherlands and comparison with the United kingdom. Cardiovasc Intervent Radiol. 2013 Dec;36(6):1477-1492. doi: 10.1007/s00270-013-0558-6. Epub 2013 Feb 13.
- Background: PubMed 22831869Wiersema 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.
- Background: PubMed 23408671Finley 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.
- Background: PubMed 507308Mabry CD, Thompson BW, Read RC. Activated clotting time (ACT) monitoring of intraoperative heparinization in peripheral vascular surgery. Am J Surg. 1979 Dec;138(6):894-900. doi: 10.1016/0002-9610(79)90318-0.
- Background: PubMed 28943189Goldhammer JE, Zimmerman D. Pro: Activated Clotting Time Should Be Monitored During Heparinization For Vascular Surgery. J Cardiothorac Vasc Anesth. 2018 Jun;32(3):1494-1496. doi: 10.1053/j.jvca.2017.04.047. Epub 2017 Apr 26. No abstract available.
- Background: PubMed 28802634Veerhoek D, Groepenhoff F, van der Sluijs MGJM, de Wever JWB, Blankensteijn JD, Vonk ABA, Boer C, Vermeulen CFW. Individual Differences in Heparin Sensitivity and Their Effect on Heparin Anticoagulation During Arterial Vascular Surgery. Eur J Vasc Endovasc Surg. 2017 Oct;54(4):534-541. doi: 10.1016/j.ejvs.2017.07.006. Epub 2017 Aug 9.
- Individual participant dataSharing planned: Yes. All ACT values can be obtained after trial with PI
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arno M Wiersema, MD, PhD principal investigator
Dijklander Ziekenhuis
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Arterial Disease and Surgery, run by Dijklander Ziekenhuis at 3 sites in Netherlands.
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 1 inclusion and 1 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: finished, 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 3 sites in Netherlands. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change of Activated Clotting Time (time frame: ACT measured before heparin, 5 minutes after and than at 30 minutes intervals. After a repeated dose of heparin again after 5 minutes and 30 minutes intervals). 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 NCT03426293, which also lists 8 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.