MARINER Trial: Multiparametric Cardiac PET for CAV Surveillance After Heart Transplantation

Study Overview
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Brief Summary
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Cardiac allograft vasculopathy (CAV) is a common complication affecting heart transplant patients. This condition causes narrowing of the heart arteries leading to graft dysfunction. Surveillance for CAV is vital; however an ideal approach has not been established. The goal of this study is to assess whether noninvasive positron emission tomography (PET) based surveillance is non-inferior to invasive coronary angiography (ICA) surveillance.

Detailed Description
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MARINER is a Canadian multicentre prospective, randomized clinical outcomes-based trial evaluating noninferiority of a noninvasive PET strategy compared to ICA for CAV surveillance. Patients are randomized to annual PET or ICA for CAV surveillance. Non-inferiority is assessed according to a clinical composite of death, retransplant, allograft dysfunction not related to acute rejection, and angiographic CAV associated with myocardial infarction or heart failure. Secondary outcomes include the rate of new or progressive CAV, number of ICA performed, number of ICA and PET procedural related complications, EuroQol-5 Dimension assessed patient health-related quality of life and health care resource use.

Official Title
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Multiparametric Cardiac Positron Emission Tomography for Cardiac Allograft Vasculopathy Surveillance After Heart Transplantation

Conditions
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Cardiac Allograft Vasculopathy

Intervention / Treatment
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* Diagnostic Test: ICA
* Diagnostic Test: PET


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post heart transplant 2-10 years. Age ≥18 years. Able to provide informed consent. Exclusion Criteria: Contraindication to dipyridamole due to severe aortic stenosis. Contraindication to dipyridamole due to 2:1 or greater AV block without pacemaker. Contraindication to dipyridamole due to severe bronchospasm. Unable to undergo coronary angiography due to allergy to iodinated contrast. Unable to undergo coronary angiography due to glomerular filtration rate ≤30 mL/min/1.73 m2. for non-dialysis patients as determined by local laboratory analysis. Unable to undergo coronary angiography due to unsuitable vascular access. Treated rejection ≤1-month. Unstable angina or MI ≤7 days.

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: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 randomization to PET or ICA
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Invasive Coronary Angiography<br>Patients in this arm will undergo annual CAV surveillance with ICA | Diagnostic Test: ICA<br>* Patients will undergo annual CAV surveillance with ICA<br>|
| Other: Positron Emission Tomography<br>Patients in this arm will undergo annual CAV surveillance with PET | Diagnostic Test: PET<br>* Patients will undergo annual CAV surveillance with PET<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically relevant composite: Death | Date of death due to any cause | From date of randomization up to a minimum of 2 years | 
| Clinically relevant composite: Retransplant | Heart retransplantation for any indication | From date of randomization up to a minimum of 2 years | 
| Clinically relevant composite: Allograft Dysfunction | ≥25% decrease in left ventricular ejection fraction | From date of randomization up to a minimum of 2 years | 
| Clinically relevant composite: CAV with Heart Failure or Myocardial Infarction | Angiographic evidence of CAV (ISHLT CAV 1-3) | From date of randomization up to a minimum of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of new or progressive CAV | CAV disease severity according to ISHLT CAV 0-3 grading and/or MIT on IVUS | From date of randomization up to a minimum of 2 years | 
| Number of ICA performed | Number of ICA performed for any indication including CAV surveillance, abnormal PET or clinical indication | From date of randomization up to a minimum of 2 years | 
| Number of procedural related complications (ICA and PET) | The frequency of ICA and PET procedural related complication including vascular access complications, stroke, MI, arrhythmia, drug allergy and contrast nephropathy | From date of randomization up to a minimum of 2 years | 
| Patient Health related outcomes | EuroQol-5 Dimension is a standardized health related questionnaire measuring 5 domains of health and a state of health using a visual analog scale (best state marked 100 and worst state marked 0) | Baseline and 12-monthly up to a minimum of 2 years | 
| Health Resource Utilization | Cost effectiveness of each CAV surveillance strategy (ICA and PET) | From date of randomization up to a minimum of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Transplant