Clinical Impact of Using IMPROVE to Select Patients for Carotid Revascularisation

NCT07556887 | Not Yet Recruiting DMC

• 1 other identifier: NL-010345
• Study Type: interventional
• Target: 613
• Locations: 1 country
• Sites: 10

Brief Summary

Narrowing of the carotid artery due to atherosclerosis with an unstable plaque can cause a stroke. Patients with carotid artery disease who have had a TIA or minor stroke and are at high risk of another stroke are often treated with surgery or stenting to remove the plaque. For lower-risk patients, medication alone is the better option, as surgery also carries risks. A new decision method, based on MRI detection of unstable plaques (IMPROVE), can better assess stroke risk and help determine which patients do or do not need surgery. We are investigating whether this method is at least as effective as the standard approach, which mainly considers the degree of narrowing. We expect that this new method will help reduce strokes and lower healthcare costs. Patients will be followed for several years to compare which method is better for health and costs.

Conditions

Carotid Artery Stenosis Symptomatic; Stroke; Stroke Ischemic; Atheroscleroses; Stroke (CVA) or TIA; Intraplaque Hemorrhage; TIA (Transient Ischemic Attack); Atherosclerosis Cerebral Infarction; Carotid Arteriosclerosis; Ischemic Cerebral Infarction

Keywords

Carotid Artery Stenosis; Transient Ischemic Attack; Ischemic Stroke; Atherosclerosis; Plaque Rupture; Revascularisation; Carotid Endarterectomy; Carotid Artery Stenting; Magnetic Resonance Imaging; Stroke Risk Prediction; Intraplaque hemorrhage; Clinical Decision Support; Randomized Controlled Mulitcentre Trial; Cost-Effectiveness Analysis; Optimal Medical Therapy

Outcome Measures

Primary Outcomes (1)

• The primary outcome of the study is the composite of any stroke or death within 44 days after randomisation or ipsilateral ischemic stroke at any time during subsequent follow-up.

  The perioperative period for the primary endpoint is defined as 44 days after randomisation for both study arms, rather than (the frequently defined) 30 days after carotid revascularisation. This approach avoids bias that would arise if the perioperative window were limited only to patients undergoing revascularisation. By using a fixed 44-day period after randomisation, carotid revascularisation can take place up to two weeks after randomisation without affecting the primary outcome definition, ensuring a fair comparison between treatment arms. The endpoint includes any stroke, including haemorrhagic stroke, as well as death occurring within this period.

  any strokes/deaths: from randomisation (day 1) until day 44. Ipsilateral ischemic strokes: from randomisation (day 1) through completion of follow-up (36 up to 60 months).

Secondary Outcomes (9)

• Incidence of other cardiovascular ischemic symptoms (any stroke, myocardial infarction, TIA)

  From randomisation (Day 1) through completion of follow-up (36 up to 60 months).

• Functional outcome (mRS)

  At day 44 and 3 years after randomisation.

• The IMTA Productivity Cost Questionnaire (iPCQ)

  From baseline follow-up visit through completion of follow-up (36 up to 60 months).

• Quality of life questionnaire (EQ-5D-5L) questionnaire

  From baseline follow-up visit through completion of follow-up (36 up to 60 months).

• The iMTA Medical Consumption Questionnaire (iMCQ)

  From baseline follow-up visit through completion of follow-up (36 up to 60 months).

Other Outcomes (5)

• Proportion of patients undergoing carotid revascularisation before application of the decision rule.

  From randomisation (Day 1) up to moment of revascularisation.

• Missing MRI or other required input data for application of the decision rule, recorded as the proportion of patients with incomplete data and documented reasons.

  From randomisation (Day 1) up to moment of clinical decision making.

• Elective carotid revascularisation in low-risk patients according to the decision rule, assessed as the proportion of patients undergoing elective carotid endarterectomy or carotid artery stenting.

  From randomisation (Day 1) up to moment of revascularisation.

Study Arms (2)

Care As Usual (CAU)

NO INTERVENTION

CAU follows Dutch FMS guidelines, recommending revascularisation for symptomatic patients with ≥50% stenosis and OMT-only for 30-49%. Guidelines suggest risk models like CAR score but lack treatment guidance.

Intervention (IMPROVE) Arm:

EXPERIMENTAL

IMPROVE recommends revascularisation + OMT for patients with ≥10% 3-year ipsilateral stroke risk according to the IMPROVE-score and OMT-only for those with lower than 10% risk.

Other: IMPROVE Risk Model

Interventions

IMPROVE Risk Model OTHER

All patients are screened in routine care for stenosis. The stroke risk is assessed using IMPROVE, incorporating plaque vulnerability (intraplaque haemorrhage (IPH) on MRI), stenosis degree, ischemic event type (ocular vs. cerebral), age and sex. The practitioner and patient discuss treatment options in shared decision making based on this risk score. Patients above the risk threshold (≥10% ipsilateral stroke risk within 3 years) receive a recommendation for revascularisation, those below an advice for OMT-only. The 10% threshold resulted in the largest stroke reduction in the decision analytic study. \~53% of the patients need an extra MRI. In \~47% an MRI is unnecessary since, based on the other risk factors, the stroke risk is already high or low and the MRI result does not affect the risk category.

Also known as: IMPROVE Rule, IMPROVE Decision Rule, IMPROVE Risk Score, IMPROVE Stroke Risk Model, IMPROVE MRI-Based Model, IMPROVE Risk Stratification, IMPROVE Clinical Decision Tool, IMPROVE Risk Assessment

Intervention (IMPROVE) Arm:

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Mentally competent
• years or older
• Recent (\<30 days) stroke (modified Rankin scale ≤3) or TIA
• Ipsilateral 30-99% atheromatous stenosis at the carotid bifurcation assessed using non-invasive imaging according to NASCET criteria
• Life expectancy \>5 years
• Patient and stenosis are suitable for carotid revascularisation
• Patient is agreeable to randomisation and willing to accept either IMPROVE-based or CAU-based selection method for carotid revascularisation

You may not qualify if:

• Cardiac source of embolism
• Carotid stenosis caused by non-atherosclerotic disease e.g. dissection, fibromuscular disease or neck radiotherapy.
• MRI contra-indications
• Pregnancy

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Academisch Ziekenhuis Maastricht: collaborator
• Amsterdam UMC: collaborator
• UMC Utrecht: collaborator
• Haaglanden Medical Centre: collaborator
• Isala: collaborator
• Radboud University Medical Center: collaborator
• Zuyderland Medical Centre: collaborator
• Albert Schweitzer Hospital: collaborator
• Rijnstate Hospital: collaborator
• Erasmus Medical Center: collaborator

Study Sites (10)

Rijnstate

Arnhem, Gelderland, 6800 TA, Netherlands

Location

Radboud UMC

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Zuyderland

Heerlen, Limburg, 6419 PC, Netherlands

Location

Maastricht University

Maastricht, Limburg, 6229 ER, Netherlands

Location

Amsterdam UMC

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Isala

Zwolle, Overijssel, 8025 AB, Netherlands

Location

Albert Schweitzer Ziekenhuis

Dordrecht, South Holland, 3300 AK, Netherlands

Location

Erasmus MC

Rotterdam, South Holland, 3000 CA, Netherlands

Location

Haaglanden MC

The Hague, South Holland, 2501 CK, Netherlands

Location

Utrecht UMC

Utrecht, Utrecht, 3584 CX, Netherlands

Location

Related Publications (2)

• Bierens J, Ament SMC, Truijman MTB, de Borst GJ, Nederkoorn PJ, Bos D, Joore MA, Postma AA, Kooi ME, van Oostenbrugge RJ, Smits LJM; IMPROVE Investigators. Plaque Magnetic Resonance Imaging Based Decision Rule for the Selection of Symptomatic Patients for Carotid Revascularisation: Clinician Perspectives on Acceptability and Implementation Barriers in the Netherlands. Eur J Vasc Endovasc Surg. 2026 Jan;71(1):5-11. doi: 10.1016/j.ejvs.2025.08.022. Epub 2025 Sep 9.

  PMID: 40930395 BACKGROUND

• Nies KPH, Smits LJM, van Kuijk SMJ, Hosseini AA, van Dam-Nolen DHK, Kwee RM, Kurosaki Y, Rupert I, Nederkoorn PJ, de Jong PA, Bos D, Yamagata S, Auer DP, Schindler A, Saam T, van Oostenbrugge RJ, Kooi ME. Individualized MRI-Based Stroke Prediction Score Using Plaque Vulnerability for Symptomatic Carotid Artery Disease Patients (IMPROVE). Stroke. 2025 Aug;56(8):2068-2078. doi: 10.1161/STROKEAHA.124.050020. Epub 2025 May 8.

  PMID: 40336502 BACKGROUND

Related Links

• The IMPROVE trial website for patients, clinicians, researchers and others.

MeSH Terms

Conditions

Ischemic Stroke; Atherosclerosis; Stroke; Ischemic Attack, Transient; Carotid Artery Diseases; Carotid Stenosis

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Brain Ischemia

Study Officials

• M. Eline Kooi, Prof. dr.

  Maastricht University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

M. Eline Kooi, Prof. dr.

CONTACT

+31 43 387 4911; improve.trial@mumc.nl

Robin M.M. Pleumeekers, MSc.

CONTACT

+31 43 387 7622; robin.pleumeekers@mumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2026
• First Posted: April 29, 2026
• Study Start: March 31, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2031
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Unending (e.g., "Beginning 1 year after publication with no end date")

Locations

NL (10)