RCT of Implantable Defibrillators in Patients with Non Ischemic Cardiomyopathy, Scar and Severe Systolic Heart Failure (BRITISH)

University Hospital Southampton NHS Foundation Trust

Status: Enrolling

Conditions: Heart Failure

Treatments: Device: Implantable Cardioverter-Defibrillator (ICD) or Cardiac Resynchronisation Therapy Defibrillator (CRTD)

Study type: Interventional

Funder types: Other

Identifiers

NCT05568069

RHMCAR0581

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2,504 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,504 participants in 3 patient groups

Intervention

Experimental group

Description:

ICD or CRTD fitted

Treatment:

Device: Implantable Cardioverter-Defibrillator (ICD) or Cardiac Resynchronisation Therapy Defibrillator (CRTD)

Control

No Intervention group

Description:

No ICD fitted (with Implantable Loop Recorder) or Cardiac Resynchronisation Therapy Pacemaker (CRTP)

Registry

No Intervention group

Description:

Usual medical care