Cardiovascular Magnetic Resonance GUIDEd Insertion of Implantable Cardiac Defibrillator in Dilated CardioMyopathy

Study Overview
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Brief Summary
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CMR GUIDE DCM is a randomized controlled trial with a registry for non-randomized patients. Patients enrolled will have non-ischemic cardiomyopathy (NICM) with mild to severe Left Ventricular (LV) systolic dysfunction with replacement fibrosis identified on Cardiac Magnetic Resonance (CMR). 954 patients will be randomised from 50 sites across 4-6 countries worldwide to receive an implantable defibrillator (ICD) or implantable loop recorder (ILR). Device and clinical follow-up will be performed at 3, 6, 12, 24, 36 months and at end of study.

Detailed Description
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The planned research will have two components: A prospective, blocked, randomized, controlled trial of primary prophylaxis ICD therapy or ILR insertion in patients with LVEF <45% and Late Gadolinium Enhancement (LGE) on CMR and A prospective observational registry of patients with LVEF <45% and no LGE on CMR. Registry patients will not have an intervention but will have the same follow up frequency as the randomized patients. The Primary objective is to determine if routine CMR guided management strategy of implantable defibrillator (ICD) insertion reduces total mortality compared to a conservative strategy of implantable loop recorder (ILR) insertion and standard care. The secondary objectives include: To determine if routine CMR guided management strategy of ICD insertion reduces sudden cardiac death (SCD) compared to a conservative strategy of ILR insertion and standard care. To ascertain the rate of SCD in patients with DCM and LGE scar across a wide range of left ventricular ejection fraction (LVEF). Statistical analysis will be performed on an intention-to-treat basis. The main analysis of time to death from any cause will be performed using a log- rank test.

Official Title
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Cardiovascular Magnetic Resonance GUIDEd Insertion of Implantable Cardiac Defibrillator in Dilated CardioMyopathy

Conditions
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Dilated Cardiomyopathy, Left Ventricular Systolic Dysfunction, Fibrosis Myocardial

Intervention / Treatment
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* Device: ICD
* Device: ILR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than/equal to 18 years old Non-ischemic cardiomyopathy of dilated type Left Ventricular Ejection Fraction < 45% Able and willing to comply with all pre, post and follow-up testing and requirements On maximum tolerated doses of angiotensin converting enzyme (ACE) inhibitors (or Angiotensin Receptor Blockers(ARB) or Neprilysin Inhibitors) and Beta Blockers Exclusion Criteria: Known coronary artery disease (CAD) (History of Myocardial Infarction or Significant Epicardial CAD on Angiography) Hypertrophic Cardiomyopathy Cardiomyopathy related to sarcoidosis Arrhythmogenic Right Ventricular Dysplasia Standard LGE CMR contraindications (e.g. severe claustrophobia, metal) Currently implanted permanent pacemaker and/or pacemaker/ICD lead Clinical indication for ICD or pacemaker or Cardiac Resynchronisation Therapy Contraindications to intravenous Gadolinium Severe renal insufficiency (eGFR< 45mls/min/1.73m2 ) New York Heart Association Heart Failure functional class IV Conditions associated with life expectancy <1 year Pregnancy or in females of child-bearing potential, the non-use of accepted forms of contraception

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Device Implantation<br>A prospective, blocked, randomised, controlled trial of primary prophylaxis ICD therapy or ILR insertion in patients with LVEF <45% and LGE on CMR. | Device: ICD<br>* Insertion of ICD in patients with LVEF <45% and LGE on CMR.<br>Device: ILR<br>* Insertion of ILR in patients with LVEF <45% and LGE on CMR.<br>|
| No Intervention: Observational Registry<br>A prospective observational registry of patients with LVEF <45% and no LGE on CMR. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-Cause Mortality |  | Through to study completion, an average of 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants who have Sudden Cardiac Death |  | Through to study completion, an average of 4 years | 
| Number of Participants who have a Haemodynamically significant ventricular arrhythmia event |  | Through to study completion, an average of 4 years | 
| Quality of life assessed by Kansas City Cardiomyopathy Questionnaire | The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the above 23 items which will be between 0-100. A higher score reflects a better health status. | Measured at 3, 6, 12, 24, 36 months through to study completion | 
| Number of Participants who have a Heart Failure related hospitalisation |  | Through to study completion, an average of 4 years | 
| Health economic evaluation of cost | Various different country jurisdictions will be chosen | At study completion, an average of 4 years |