An interventional study of IMPROVE Risk Model in Carotid Artery Stenosis Symptomatic, Ischemic Cerebral Infarction and Stroke Ischemic, sponsored by Maastricht University Medical Center. Recruiting at 10 sites in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-15.
Sponsored by Maastricht University Medical Center · Not applicable, Interventional, and Diagnostic
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.
SUMMARY:
Stroke is the 2nd leading global cause of death and disability. Rupture of a vulnerable carotid plaque causes \~20% of ischemic strokes. Symptomatic patients with carotid stenosis may benefit from surgical removal of the plaque or stenting (revascularisation) to prevent recurrent stroke, but this carries risks. Current patient selection for revascularisation is suboptimal, largely based on stenosis degree without considering plaque vulnerability. Improving risk prediction is therefore crucial and has been formally recognized as a key priority in the Dutch Society for Vascular Surgery's Knowledge Agenda (2022): "How can we better identify patients with carotid stenosis who would or would not benefit from revascularisation?" Presence of intraplaque haemorrhage (IPH) on MRI is one of the most powerful imaging biomarkers of plaque vulnerability and a superior predictor of stroke compared to traditional clinical factors, including degree of stenosis. The recently developed "Individualized MRI- Based Stroke Prediction Score Using Plaque Vulnerability for Symptomatic Carotid Artery Disease Patients" (IMPROVE) clinical prediction model integrates both IPH on MRI and clinical risk factors to calculate ipsilateral ischemic stroke risk. This model has demonstrated significantly improved predictive performance over existing scores. A recent decision-analytic study investigated the impact of the use of IMPROVE to select patients with high stroke risk for revascularisation plus OMT (medication and lifestyle advice) and low-risk patients for OMT (optimized medical therapy)-only. This decision-analytic study showed that implementation of the IMPROVE decision rule for revascularisation selection can lead to 35% less ipsilateral strokes and perioperative strokes and deaths and a lifetime cost reduction of €6101 per patient, equating to an annual reduction in societal healthcare costs of €18 million in the Netherlands alone.
Rationale: Patient selection for carotid revascularisation to prevent recurrent strokes could be optimised by providing clinicians and patients the IMPROVE score for shared decision-making. Objective: The primary objective is to investigate the clinical impact and the cost-effectiveness of the individualised MRI-based IMPROVE decision rule compared to care as usual (CAU) in the selection of TIA and non-disabling stroke patients with 30-99% carotid stenosis for revascularisation.
Study design: Multicentre, randomized controlled non-inferiority trial. Study population: Patients with a recent TIA or minor ischemic stroke and ipsilateral 30-99% carotid stenosis according to NASCET criteria.
Intervention: For patients that are randomised to the IMPROVE arm, the IMPROVE risk score will be provided as additional information for clinical decision-making on patient stratification for carotid revascularisation plus OMT versus OMT-only. A revascularization procedure in combination with OMT will be advised for patients at high ipsilateral stroke risk (≥10% within 3 years) according to the IMPROVE score, while OMT- only (medication and lifestyle advice) is advised to patients with lower risk scores.
Comparator: Patients randomised for the control arm (care-as-usual (CAU)) will be selected for revascularisation based on the guidelines for carotid interventions from the European Society for Vascular Surgery. It advises to consider revascularisation for TIA and stroke patients with ≥50% carotid stenosis. Patients with 30-49% stenosis are treated by OMT-only (medication and lifestyle advice). Plaque vulnerability is not taken into account for patient selection in current clinical care in the Netherlands.
Main study parameters/endpoints: Primary: Composite of any stroke or death within 44 days after randomisation or ipsilateral ischemic stroke at any time during subsequent 3-5 years follow up. Secondary: a.o. QALYs, number of revascularization procedures, costs.
2,612 studies on the registry are indexed under Ischemic Stroke; 971 are open to participants now.
This study's planned enrollment of 613 is above the median of 120 across 1,776 interventional studies indexed under Ischemic Stroke.
Browse Ischemic Stroke studies →Maastricht University Medical Center is the lead sponsor of 853 studies on the registry; 114 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
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
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
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.
Time frame: 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).
Incidence of other cardiovascular ischemic symptoms (any stroke, myocardial infarction, TIA)
Time frame: From randomisation (Day 1) through completion of follow-up (36 up to 60 months).
Functional outcome (mRS)
The modified Rankin Scale (mRS) is a measure used to assess a patients functional outcome after a stroke. It is an observational scale in which patients are classified into seven categories according to their functional status. A score of "0" corresponds to no symptoms, and a score of "6" corresponds to death.
Time frame: At day 44 and 3 years after randomisation.
The iMTA (Institute for Medical Technology Assessment) Productivity Cost Questionnaire (iPCQ)
The goal of the iMTA Productivity Cost Questionnaire (iPCQ) is to measure productivity losses due to health problems for use in economic evaluations and health economic studies. Outcomes are reported in (working) days/hours or efficiency loss and there is no fixed total score. Higher values indicate worse productivity loss (e.g. more days absent due to illness or more symptoms during work).
Time frame: From baseline follow-up visit through completion of follow-up (36 up to 60 months).
Quality of life (EQ-5D-5L: EuroQol [Quality of Life-5 dimensions-5 levels]) questionnaire
The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems (=0) up to extreme problems (=5). The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state (Dutch value set). The EQ VAS (virtual analogue scale) records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'The best health you can imagine' = 100 and 'The worst health you can imagine' = 0. The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement.
Time frame: From baseline follow-up visit through completion of follow-up (36 up to 60 months).
The iMTA Medical Consumption Questionnaire (iMCQ)
The iMCQ collects data on medical resource use so that direct healthcare costs can be calculated. Assesses healthcare utilization (e.g., visits, hospitalizations, medication use). Outcomes are reported as frequencies/volumes and there is no fixed total score. Higher volumes/frequenties indicate more healthcare use (and therefore higher costs).
Time frame: From baseline follow-up visit through completion of follow-up (36 up to 60 months).
Number of hospitalizations
Time frame: From randomisation (Day 1) through completion of follow-up (36 up to 60 months).
Number of carotid revascularisation procedures
The number of carotid revascularisations (carotid endarterectomy (CEA) and stenting) will be determined.
Time frame: From randomisation (Day 1) through completion of follow-up (36 up to 60 months).
Incremental cost-effectiveness ratio
Time frame: From randomisation (Day 1) through completion of follow-up (36 up to 60 months).
Perioperative complications
Time frame: From randomisation (Day 1) through completion of follow-up (36 up to 60 months).
Proportion of patients undergoing carotid revascularisation before application of the decision rule.
Process variables will be measured for the purpose of facilitating further implementation. These process variables are measured only in the intervention group.
Time frame: 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.
Process variables will be measured for the purpose of facilitating further implementation. These process variables are measured only in the intervention group.
Time frame: 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.
Process variables will be measured for the purpose of facilitating further implementation. These process variables are measured only in the intervention group.
Time frame: From randomisation (Day 1) up to moment of revascularisation.
Non-adherence to the risk-based recommendation, assessed as the proportion of patients with treatment decisions deviating from the decision rule.
Process variables will be measured for the purpose of facilitating further implementation. These process variables are measured only in the intervention group.
Time frame: At moment of clinical decision making (within 14 days after first consult with neurologist).
Inability to apply the decision rule, assessed as the proportion of patients for whom the decision rule could not be applied, with documented reasons.
Process variables will be measured for the purpose of facilitating further implementation. These process variables are measured only in the intervention group.
Time frame: At moment of clinical decision making (within 14 days after first consult with neurologist).
Plan to share: Yes — Data will not be publicly available but can be obtained from the principal investigator upon reasonable request.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Unending (e.g., "Beginning 1 year after publication with no end date")
Data sharing details ↗ · improve-trial.nl
Started Mar 2026 (actual). Primary completion is estimated for Aug 2028, 29 months after the start.
Of 572 non-industry interventional studies with no phase under Ischemic Stroke, half reached primary completion within 28 months of starting (the median), counting those still running; a quarter within 14 and three quarters within 48. This study's planned 29 months is close to that.
Counting every sponsor, half of 653 studies reached it within 27 months; a quarter within 14 and three quarters within 48.
How these figures are worked out, and which studies are left out of them.
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