Clinical trial NCT05568069: RCT of Implantable Defibrillators in Patients With Non Ischemic Cardiomyopathy, Scar and Severe Systolic Heart Failure
Official title: Using Cardiovascular Magnetic Resonance Identified Scar as the Benchmark Risk Indication Tool for Implantable Cardioverter Defibrillators in Patients With Non-Ischemic Cardiomyopathy and Severe Systolic Heart Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Keywords: Cardiac Magnetic Resonance Imaging (CMR)
Implantable Cardioverter Device
Implantable Loop Recorder
Left ventricular ejection fraction (LVEF)
Myocardial scar
Lead sponsor: University Hospital Southampton NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: British Heart Foundation
name: University of Southampton
First posted: 2022-10-05
Enrollment: 2504
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible patients will be randomised in a controlled fashion into two arms (n=1252):

Arm A: ICD implantation Arm B: No ICD implantation Patients with no scar on CMR will be followed up in a registry (n=1252)
Primary purpose: TREATMENT

Brief summary: BRITISH is a UK multicentre trial of patients who have been diagnosed with heart failure due to Non-Ischemic Cardiomyopathy (NICM, or heart failure that is not caused by blocked heart arteries. Participants will be randomised into two groups. Half the participants will receive an Implantable Cardioverter-Defibrillator (ICD) and the other half will not. The aim of the study will be to compare all-cause mortality (death from any cause) between these two groups at 36 months, and longer-term to 10 years. The study has the potential to change international heart failure treatment guidelines and to improve how patients with this condition are managed.

Detailed description: Patients with Non-Ischemic Cardiomyopathy (NICM) have a higher risk of experiencing serious abnormal heart rhythms that might be life-threatening. Current guidelines recommend fitting a device that can correct these serious heart rhythms (Implantable Cardioverter-Defibrillator (ICD)). However, research studies have shown that 90% of patients who have an ICD will never use it because they won't experience any serious heart rhythms. A recent large trial (DANISH) of over one thousand patients with severe Non-Ischemic Cardiomyopathy has called the current guidelines into question. The trial concluded that for patients who received an ICD, there was no difference in the likelihood of dying when compared to patients that didn't have an ICD fitted. As a result, many doctors are choosing not to implant an ICD in patients with this type of heart failure, as they believe there is no overall survival benefit. However, there are clues that some patients with NICM may still benefit from an ICD, even though the headline results suggest they are not necessary. It's likely that it's the patients who are at increased risk of having a serious abnormal heart rhythm that stand to benefit from ICDs. But having an ICD fitted carries with it a significant risk of problems developing e.g. bleeding, infection, lead problems, and inappropriate shocks. These risks may not outweigh the benefits and it is this question which BRITISH will address. The study will randomly assign (like the toss of a coin), half the study participants to receive an ICD and the other half to no ICD.

Both groups will be followed up to decide whether having an ICD fitted reduces the chances of dying.

Eligibility criteria: Inclusion Criteria:

1. A diagnosis of NICM on contrast-enhanced cardiovascular magnetic resonance imaging
2. LV scar on routine CMR (patient without scar can enter the registry)
3. New York Heart Association (NYHA) Heart Failure (HF) functional class I-III and severely impaired left ventricular function (LVEF ≤ 35% on any imaging modality) after a minimum of 3 months of treatment with optimal medical therapy (OMT) as recommended by National Institute for Health and Care Excellence (NICE)
4. Able and willing to provide informed consent

Exclusion Criteria:

1. New York Heart Association (NYHA) HF functional class IV after 3 months of optimal medical therapy (OMT)
2. Acute decompensated heart failure
3. Previous implantable device in situ (PPM, Cardiac Resynchronisation Therapy (CRT) or ICD)
4. Ischemic cardiomyopathy (ICM) is defined as segmental wall motion abnormalities or wall thinning in a particular coronary territory with subendocardial or transmural late gadolinium enhancement (LGE). Patients with an LVEF ≤35% and a small amount of ischemic LGE (i.e. an infarct out of keeping with the amount of LV dysfunction) will not be excluded (so-called dual pathology patients)
5. Known diagnosis of amyloidosis, sarcoidosis, arrhythmogenic right ventricular cardiomyopathy, or hypertrophic cardiomyopathy (diseases in which there are specific guidelines regarding defibrillator therapy)
6. Known Lamin gene mutation or a positive family history of a Lamin gene mutation
7. Valve disease is considered likely to require surgery during the 3 years follow-up period
8. Complex congenital heart disease
9. Any secondary prevention ICD indication
10. Heart transplant recipient or admitted for cardiac transplantation/ left ventricular assist device
11. Clinically apparent myocardial ischemia which requires revascularization
12. Intracardiac mass which requires surgery
13. Active endocarditis
14. Active Septicaemia
15. Pregnancy
16. Life expectancy \<2 years secondary to any other cause (i.e. malignancy)
17. Active treatment with chemotherapy
18. Severe renal failure (GFR \<30)
19. Actively participating in another study without prior agreement between both Chief Investigators

Primary outcomes:
measure: Percentage of patients alive
timeFrame: 3 years
Secondary outcomes:
measure: Change in health-related quality of life measured using KCCQ-12
timeFrame: 3 years
measure: Change in health-related quality of life measured using EQ-5D-5L
timeFrame: 3 years
measure: Cardiovascular Death
timeFrame: 3 years
measure: Sudden cardiac death
timeFrame: 3 years
measure: Aborted sudden cardiac death
timeFrame: 3 years
measure: Appropriate ICD Therapy
timeFrame: 3 years
measure: Inappropriate ICD Therapy
timeFrame: 3 years
measure: Significant ventricular arrhythmias
timeFrame: 3 years
measure: NYHA Status
timeFrame: 3 years
measure: Heart failure hospitalisations
timeFrame: 3 years
measure: Cardiac hospitalisations
timeFrame: 3 years
measure: Procedures related to implanted device
timeFrame: 3 years
measure: Percentage of patients alive
timeFrame: At 5 and 10 years
Other outcomes:
Locations:
city: High Wycombe
country: United Kingdom
facility: Wycombe Hospital
state: Buckinghamshire
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: Devon
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: Dorset
city: Darlington
country: United Kingdom
facility: Durham & Darlington NHS Foundation Trust
state: Durham
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
state: East Sussex
city: Basildon
country: United Kingdom
facility: Essex Cardiothoracic Centre
state: Essex
city: Gorleston-on-Sea
country: United Kingdom
facility: James Paget University Hospitals NHS FT
state: Great Yarmouth
city: Portsmouth
country: United Kingdom
facility: Portsmouth Hospitals University NHS Trust
state: Hampshire
city: Southampton
country: United Kingdom
facility: Southampton Clinical Trials Unit
state: Hampshire
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
city: Canterbury
country: United Kingdom
facility: Kent & Canterbury Hospital
state: Kent
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital, Maidstone & Tunbridge Wells NHS Trust
state: Kent
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospiatal
state: Lancashire
city: Liverpool
country: United Kingdom
facility: Liverpool Heart & Chest
state: Lancashire
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
state: Leicestershire
city: Tooting
country: United Kingdom
facility: St George's Hospital
state: London
city: Newcastle
country: United Kingdom
facility: Newcastle Freeman Hospital
state: Newcastle upon Tyne
city: Middlesbrough
country: United Kingdom
facility: The James Cook University Hospital
state: North Yorkshire
city: Ashington
country: United Kingdom
facility: Wansbeck General Hospital
state: Northumbria
city: Scarborough
country: United Kingdom
facility: Scarborough Hospital
state: Nortrh Yorkshire
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
state: Nottinghamshire
city: Oxford
country: United Kingdom
facility: The John Radcliffe Hospital
state: Oxfordshire
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
state: Scotland
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
state: Somerset
city: Sheffield
country: United Kingdom
facility: Northern General Hospital
state: South Yorkshire
city: Hardwick
country: United Kingdom
facility: University Hospital of North Tees
state: Stockton-on-Tees
city: Camberley
country: United Kingdom
facility: Frimley Park Hospital
state: Surrey
city: Redhill
country: United Kingdom
facility: Surrey & Sussex Healthcare NHS Trust
state: Surrey
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
city: Coventry
country: United Kingdom
facility: University Hospital Coventry
state: Warwickshire
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
state: West Midlands
city: Chichester
country: United Kingdom
facility: St Richards Hospital
state: West Sussex
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
state: West Yorkshire
city: Wakefield
country: United Kingdom
facility: Pinderfields Hospital
state: West Yorkshire
city: Worcester
country: United Kingdom
facility: Worcestershire Royal Hospital
state: Worcestershire
city: Manchester
country: United Kingdom
facility: Wythenshaw Hospital
state: Wythenshaw
city: Hull
country: United Kingdom
facility: Castle Hill Hospital
state: Yorkshire
city: Exeter
country: United Kingdom
facility: Royal Devon & Exeter Hospital
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital, Imperial College Healthcare NHS Trust
city: Manchester
country: United Kingdom
facility: Fairfield General Hospital, Northern Care Alliance NHS FT
city: Swansea
country: United Kingdom
facility: Morriston Hospital
Study officials:
affiliation: University Hospital Southampton NHS Foundation Trust
name: Andrew Flett
role: STUDY_CHAIR
References: