Clinical trial NCT03993730: Cardiovascular Magnetic Resonance GUIDEd Insertion of Implantable Cardiac Defibrillator in Dilated CardioMyopathy
Official title: Cardiovascular Magnetic Resonance GUIDEd Insertion of Implantable Cardiac Defibrillator in Dilated CardioMyopathy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Dilated Cardiomyopathy
Left Ventricular Systolic Dysfunction
Fibrosis Myocardial
Lead sponsor: Flinders University
Sponsor class: OTHER
First posted: 2019-06-21
Enrollment: 1880
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: All-Cause Mortality
timeFrame: Through to study completion, an average of 4 years
Secondary outcomes:
measure: Number of Participants who have Sudden Cardiac Death
timeFrame: Through to study completion, an average of 4 years
measure: Number of Participants who have a Haemodynamically significant ventricular arrhythmia event
timeFrame: Through to study completion, an average of 4 years
measure: Quality of life assessed by Kansas City Cardiomyopathy Questionnaire
timeFrame: Measured at 3, 6, 12, 24, 36 months through to study completion
measure: Number of Participants who have a Heart Failure related hospitalisation
timeFrame: Through to study completion, an average of 4 years
measure: Health economic evaluation of cost
timeFrame: At study completion, an average of 4 years
Other outcomes:
Locations:
Study officials:
affiliation: Flinders Medical Centre
name: Joseph B Selvanayagam, MBBS
role: PRINCIPAL_INVESTIGATOR
References: