Cardiovascular Magnetic Resonance GUIDEd Insertion of Implantable Cardiac Defibrillator in Dilated CardioMyopathy (CMR GUIDE DCM)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Dilated Cardiomyopathy; Left Ventricular Systolic Dysfunction; Fibrosis Myocardial
• Intervention / Treatment: Device: ICD; Device: ILR

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 1880
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joseph B Selvanayagam, MBBS; Phone Number: +61 8 8404 2195; Email: joseph.selvanayagam@flinders.edu.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. Known coronary artery disease (CAD) (History of Myocardial Infarction or Significant Epicardial CAD on Angiography)
2. Hypertrophic Cardiomyopathy
3. Cardiomyopathy related to sarcoidosis
4. Arrhythmogenic Right Ventricular Dysplasia
5. Standard LGE CMR contraindications (e.g. severe claustrophobia, metal)
6. Currently implanted permanent pacemaker and/or pacemaker/ICD lead
7. Clinical indication for ICD or pacemaker or Cardiac Resynchronisation Therapy
8. Contraindications to intravenous Gadolinium
9. Severe renal insufficiency (eGFR< 45mls/min/1.73m2 )
10. New York Heart Association Heart Failure functional class IV
11. Conditions associated with life expectancy <1 year
12. Pregnancy or in females of child-bearing potential, the non-use of accepted forms of contraception

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Device Implantation; 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; Insertion of ICD in patients with LVEF <45% and LGE on CMR.; Device: ILR; Insertion of ILR in patients with LVEF <45% and LGE on CMR.
No Intervention: Observational Registry; A prospective observational registry of patients with LVEF <45% and no LGE on CMR.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Flinders University
• Investigators: Principal Investigator: Joseph B Selvanayagam, MBBS, Flinders Medical Centre

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2020
• Primary Completion (Anticipated): June 1, 2026
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: May 3, 2019
• First Submitted That Met QC Criteria: June 20, 2019
• First Posted (Actual): June 21, 2019

Study Record Updates

• Last Update Posted (Actual): June 21, 2019
• Last Update Submitted That Met QC Criteria: June 20, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Cardiomegaly; Laminopathies; Cardiomyopathies; Cardiomyopathy, Dilated
• Other Study ID Numbers: CMRG-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No