Cardiac Magnetic Resonance GUIDEd Management of Mild-moderate Left Ventricular Systolic Dysfunction.

Heart Failure Clinical Trial

— CMR_GUIDE  

Official title:

Cardiac Magnetic Resonance GUIDEd Management of Mild-moderate Left Ventricular Systolic Dysfunction

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01918215
• Other study ID #: CMRG-HF-1
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 2015
• Est. completion date: August 2025

Study information

• Verified date: March 2023
• Source: Flinders University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 449
• Est. completion date: August 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Left Ventricular Systolic Dysfunction
• Systolic Murmurs
• Ventricular Dysfunction, Left

Intervention

Device:
• ICD

• ILR

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Lyell McEwin Hospital	Elizabeth Vale	South Australia
Australia	St Vincent's Hospital	Fitzroy	Victoria
Australia	Royal Brisbane & Women's Hospital	Herston	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	The Alfred	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	John Hunter Hospital	New Lambton	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Germany	Coburg Hospital	Coburg
Germany	Schwarzwald-Baar Klinikum	Villingen-Schwenningen
Germany	University Hospital Wurzburg	Wurzburg
United Kingdom	Belfast Health and Social Care Trust	Belfast
United Kingdom	The Bristol Heart Institute	Bristol
United Kingdom	Golden Jubilee National Hospital	Clydebank
United Kingdom	Glenfield General Hospital	Leicester
United Kingdom	University Hospital of South Manchester NHS Foundation Trust	Manchester

Sponsors (2)

Lead Sponsor	Collaborator
Flinders University	South Australian Health and Medical Research Institute

Countries where clinical trial is conducted

Australia,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of Sudden Cardiac Death or haemodynamically significant ventricular arrhythmia	Defined as: ventricular arrhythmia producing syncope (loss of consciousness) or associated with hypotension (SBP<90mmHg) except directly associated with device implant procedure.	Through to study completion, an average of 4 years
Secondary	Sudden Cardiac Death		Through to study completion, an average of 4 years
Secondary	Haemodynamically significant ventricular arrhythmia		Through to study completion, an average of 4 years
Secondary	All-cause mortality		Through to study completion, an average of 4 years
Secondary	Change in New York Heart Association Functional class		3, 6,12, 24, 36, 48 months
Secondary	Heart failure related hospitalizations		Through to study completion, an average of 4 years
Secondary	Health economic evaluation of cost	Australia only	At study completion, average of 4 years
Secondary	Quality of life assessed by Minnesota Living with Heart Failure Questionnaire		3, 6,12, 24, 36, 48 months
Secondary	Quality of life assessed by EuroQol-5D-5L questionnaire		3, 6,12, 24, 36, 48 months