iFR Guided Multi-vessel Revascularization During Percutaneous Coronary Intervention for Acute Myocardial Infarction

Study Overview
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Brief Summary
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In patients with acute ST-elevation myocardial infarction (STEMI), 40-60% have multi-vessel disease with an increased cardiovascular morbidity and mortality. Although it is not recommended to revascularize noninfarct lesions during the acute intervention, recent investigations suggest the opposite and show improved outcome after direct revascularization of noninfarct lesions. It is undesirable to risk procedure-related complications by treating noninfarct lesions without impaired flow. It is currently unknown whether pressure guided revascularization of noninfarct lesions in the acute phase improves outcome compared to the current guidelines. The iMODERN trial aims to compare an iFR-guided intervention of noninfarct lesions during the acute intervention with a deferred stress perfusion CMR-guided strategy during the outpatient follow-up, to determine the optimal therapeutic approach for STEMI patients with multivessel lesions.

Detailed Description
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Study design: The study is a prospective, randomized controlled, multicentre study. Study population: The research population will be recruited from the general patient population presenting with an acute STEMI. Patients treated with successful primary PCI and one or more additional significant coronary lesions in another coronary artery will be enrolled in the study. A total of 1,146 consecutive patients will be included. Intervention: The patients will be randomized 1:1, to (A) an active treatment arm with complete, iFR-guided revascularization of every noninfarct coronary lesion >50% and iFR ≤0.89; (B) a deferred treatment arm, in which patients will undergo an adenosine stress perfusion CMR scan within 6 weeks after STEMI, with revascularization of the noninfarct coronary lesions with associated perfusion defects. Main study parameters/endpoints: The primary end point consists of a combined outcome, including all-cause death, recurrent MI and hospitalization for heart failure at 3 years follow-up. Duration: Anticipated recruitment is 2 years. Follow-up will be performed at 6 months, 12 months, 3 years and 5 years.

Official Title
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Instantaneous Wave-free Ratio Guided Multi-vessel revascularizatiOn During Percutaneous Coronary intervEntion for Acute myocaRdial iNfarction (iMODERN)

Conditions
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Acute Myocardial Infarction, Multi Vessel Coronary Artery Disease

Intervention / Treatment
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* Diagnostic Test: iFR
* Diagnostic Test: CMR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical presentation of STEMI and successful primary PCI within 12 hours from onset of symptoms. One or more other, noninfarct coronary artery lesions of >50% stenosis and feasible to be revascularized (i.e. minimal diameter 2mm). Exclusion Criteria: History of myocardial infarction. Hemodynamic instability, respiratory failure, Kilips class ≥III. Known GFR<30 ml/min. Known contra-indications for stress CMR (e.g.: severe claustrophobia, metal implants, severe renal failure, severe astma). Refusal or inability to provide informed consent. Life expectancy due to noncardiovascular co-morbidity of less than 12 months. Chronic total occlusion. Left main stem stenosis (>50%). Residual noninfarct lesion in infarct coronary artery. Complex (e.g. bifurcation) noninfarct target lesions.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 randomization to (A) an active treatment arm with complete, iFR-guided revascularization of every noninfarct coronary lesion >50% and iFR ≤0.89; or (B) a deferred treatment arm, in which patients will undergo an adenosine stress perfusion CMR scan within 6 weeks after STEMI, with revascularization of the noninfarct coronary lesions with associated perfusion defects.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active iFR-guided revascularization<br>Decision to treat the nonculprit coronary stenosis if there is a significant pressure drop over the stenosis, as measured by intracoronary iFR assessment | Diagnostic Test: iFR<br>* Treatment guided by instantaneous wave-free ratio<br>|
| Active Comparator: Deferred CMR-guided revascularization<br>Decision to treat the nonculprit coronary stenosis if perfusion defect visible in corresponding coronary territory as visualized on stress perfusion CMR imaging | Diagnostic Test: CMR<br>* Treatment guided by stress perfusion CMR<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite end point of Major Adverse Cardiac Events | All-cause death, recurrent myocardial infarction and hospitalization for heart failure | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality | All cause mortality at 6 and 12 months, 3 and 5 years | 6 and 12 months, 3 and 5 years | 
| Cardiovascular mortality | Cardiovascular mortality at 6 and 12 months, 3 and 5 years | 6 and 12 months, 3 and 5 years | 
| Myocardial infarction | Myocardial infarction at 6 and 12 months, 3 and 5 years | 6 and 12 months, 3 and 5 years | 
| Cerebral events | Stroke and transient ischemic attack | 6 and 12 months, 3 and 5 years | 
| Major bleeding | Haemorrhagic complications | 6 months | 
| Unstable angina | Unstable angina including ECG-changes at 6 and 12 months, 3 and 5 years | 6 and 12 months, 3 and 5 years | 
| Coronary angiography | Coronary angiography at 6 and 12 months, 3 and 5 years | 6 and 12 months, 3 and 5 years | 
| Revascularization | Any revascularization at 6 and 12 months, 3 and 5 years | 6 and 12 months, 3 and 5 years | 
| Target lesion failure | Failure and/or revascularization by percutaneous or surgical methods of the target lesion | 6 and 12 months, 3 and 5 years | 
| Stent thrombosis | Stent thrombosis at 6 and 12 months, 3 and 5 years | 6 and 12 months, 3 and 5 years | 
| Cost effectiveness analysis | Costs related to complete, iFR-guided revascularization versus CMR-guided treatment, including cost utility analysisfrom a societal perspective with the costs per prevented cardiac eventand the costs per QALY as the respective primary health economic outcomes (using a quality of life questionnaire and a health care resource use questionnaire) | 6 and 12 months, 3 and 5 years | 
| Quality of life | Quality of life questionnaires, i.e. SAQ, EQ-5D-5L and Minnesota heart failure questionnaire, at 6 and 12 months, 3 and 5 years | 6 and 12 months, 3 and 5 years |