Clinical trial NCT01918215: Cardiac Magnetic Resonance GUIDEd Management of Mild-moderate Left Ventricular Systolic Dysfunction.
Official title: Cardiac Magnetic Resonance GUIDEd Management of Mild-moderate Left Ventricular Systolic Dysfunction
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Heart Failure
Left Ventricular Systolic Dysfunction
Lead sponsor: Flinders University
Sponsor class: OTHER
Collaborators: name: South Australian Health and Medical Research Institute
First posted: 2013-08-07
Enrollment: 449
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: Contemporary heart failure (HF) guidelines recommend insertion of a primary prevention implantable defibrillator (ICD) in patients with left ventricular ejection fraction less than 35% (LVEF \< 35%) on maximally tolerated medical therapy. Nevertheless, there are a substantial number of HF patients who have LVEF\>35% and hence do not qualify for ICD, who succumb to sudden cardiac death (SCD). At present our tools to reliably risk stratify these patients with mild-moderate systolic dysfunction (LVEF 36-50%) are poor. It is likely that these patients have ventricular scar and/or replacement fibrosis as a substrate for their malignant arrhythmia. Cardiovascular magnetic resonance imaging (CMR) can reliably identify and quantify both ventricular scar (seen in Ischaemic cardiomyopathy, ICM) and replacement myocardial fibrosis (seen in Non-Ischemic Cardiomyopathy, NICM).

Methods/Design: A multi-centre randomised controlled trial in which 428 patients with mild-moderate left-ventricular systolic dysfunction (either ICM or NICM) and ventricular scar/fibrosis on cardiovascular magnetic resonance are randomized to either ICD or implantable loop recorder (ILR) insertion and are followed up until the last patient recruited has been in the study for 3 years.

Potentially eligible patients will have a screening CMR and will be enrolled into the device arm of study based on the presence of any ventricular scar/fibrosis (CMR +). Patients who do not have ventricular scar/fibrosis will be followed up in an observational registry, and will not be randomised.

In both the device and registry arms, we aim to enrol 700 patients in Australia and 355 in Europe.

The primary hypothesis is that among patients with mild-moderate left ventricular systolic dysfunction, a routine CMR guided management strategy of ICD insertion is superior to a conservative strategy of standard care.


Eligibility criteria: Inclusion Criteria:

* Age equal or greater than 18 years
* Patients with coronary artery disease (CAD) or dilated cardiomyopathy (DCM) of the idiopathic, chronic post myocarditis or familial type.
* Left ventricular systolic impairment as defined by left ventricular ejection fraction 36-50% by any current standard technique (echocardiogram, multiple gated acquisition scan (MUGA), angiography or CMR taken in the last six months. If a LGE CMR has been taken within 2 months this scan can be used for inclusion
* Able and willing to comply with all pre-, post- and follow-up testing, and requirements
* On maximum tolerated doses of ACE inhibitors (or Angiotensin and Receptor Blockers if intolerant of ACE) and Beta Blockers

Exclusion Criteria:

1. History of cardiac arrest or spontaneous or inducible sustained ventricular tachycardia or ventricular fibrillation unless within 48 hours of an acute MI
2. Cardiomyopathy related to sarcoidosis
3. Standard Cardiac Magnetic Resonance imaging contraindications (e.g. severe claustrophobia)
4. Currently implanted permanent pacemaker and/or pacemaker/ICD lead
5. Clinical indication for ICD or Pacemaker or cardiac resynchronisation therapy.
6. CMR LVEF ≤35% or\>50%
7. Severe renal insufficiency (eGFR\< 30mls/min/1.73m2)
8. Recent Myocardial Infarction (MI) (\<40 days) or cardiac revascularization (\<90 days)
9. New York Heart Association HF functional class IV at baseline
10. Conditions associated with life expectancy \<1 year
11. Pregnancy or in females of child-bearing potential, the non-use of accepted forms of contraception

Primary outcomes:
measure: Composite of Sudden Cardiac Death or haemodynamically significant ventricular arrhythmia
timeFrame: Through to study completion, an average of 4 years
Secondary outcomes:
measure: Sudden Cardiac Death
timeFrame: Through to study completion, an average of 4 years
measure: Haemodynamically significant ventricular arrhythmia
timeFrame: Through to study completion, an average of 4 years
measure: All-cause mortality
timeFrame: Through to study completion, an average of 4 years
measure: Change in New York Heart Association Functional class
timeFrame: 3, 6,12, 24, 36, 48 months
measure: Heart failure related hospitalizations
timeFrame: Through to study completion, an average of 4 years
measure: Health economic evaluation of cost
timeFrame: At study completion, average of 4 years
measure: Quality of life assessed by Minnesota Living with Heart Failure Questionnaire
timeFrame: 3, 6,12, 24, 36, 48 months
measure: Quality of life assessed by EuroQol-5D-5L questionnaire
timeFrame: 3, 6,12, 24, 36, 48 months
Other outcomes:
Locations:
city: New Lambton
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Fitzroy
country: Australia
facility: St Vincent's Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Coburg
country: Germany
facility: Coburg Hospital
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinikum
city: Wurzburg
country: Germany
facility: University Hospital Wurzburg
city: Belfast
country: United Kingdom
facility: Belfast Health and Social Care Trust
city: Bristol
country: United Kingdom
facility: The Bristol Heart Institute
city: Clydebank
country: United Kingdom
facility: Golden Jubilee National Hospital
city: Leicester
country: United Kingdom
facility: Glenfield General Hospital
city: Manchester
country: United Kingdom
facility: University Hospital of South Manchester NHS Foundation Trust
Study officials:
affiliation: Flinders Medical Centre
name: Joseph B Selvanayagam, MBBS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Selvanayagam JB, Hartshorne T, Billot L, Grover S, Hillis GS, Jung W, Krum H, Prasad S, McGavigan AD. Cardiovascular magnetic resonance-GUIDEd management of mild to moderate left ventricular systolic dysfunction (CMR GUIDE): Study protocol for a randomized controlled trial. Ann Noninvasive Electrocardiol. 2017 Jul;22(4):e12420. doi: 10.1111/anec.12420. Epub 2017 Jan 24.