BRITISH: RCT of Implantable Defibrillators in Patients With Non Ischemic Cardiomyopathy, Scar and Severe Systolic Heart Failure

Sponsor

University Hospital Southampton NHS Foundation Trust (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05568069

Collaborator

British Heart Foundation (Other), University of Southampton (Other)

2,504

Enrollment

Location

Arms

156

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Device: Implantable Cardioverter-Defibrillator (ICD) or Cardiac Resynchronisation Therapy Defibrillator (CRTD)	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2504 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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)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)

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Apr 1, 2026

Anticipated Study Completion Date :

Apr 1, 2036

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention ICD or CRTD fitted	Device: Implantable Cardioverter-Defibrillator (ICD) or Cardiac Resynchronisation Therapy Defibrillator (CRTD) An ICD is a device that is implanted under the skin under a local anesthetic. It has a battery/generator component and leads which are fixed into the heart chambers. It has the ability to detect dangerous heart rhythms if they occur, and deliver a shock to treat this to help prevent sudden cardiac death. A CRTD is a pacemaker with a defibrillator function.
No Intervention: Control No ICD fitted (with Implantable Loop Recorder) or Cardiac Resynchronisation Therapy Pacemaker (CRTP)
No Intervention: Registry Usual medical care

Arm

Intervention/Treatment

Experimental: Intervention

ICD or CRTD fitted

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

An ICD is a device that is implanted under the skin under a local anesthetic. It has a battery/generator component and leads which are fixed into the heart chambers. It has the ability to detect dangerous heart rhythms if they occur, and deliver a shock to treat this to help prevent sudden cardiac death. A CRTD is a pacemaker with a defibrillator function.

No Intervention: Control

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

No Intervention: Registry

Usual medical care

Outcome Measures

Primary Outcome Measures

Percentage of patients alive [3 years]
All-cause mortality

Secondary Outcome Measures

Change in health-related quality of life measured using KCCQ-12 [3 years]
Short questionnaire including questions related to heart failure symptoms and how they affect daily activities
Change in health-related quality of life measured using EQ-5D-5L [3 years]
Questionnaire consisting of 5 questions to evaluate a patients quality of life
Cardiovascular Death [3 years]
Percentage of patients that have cardiovascular death
Sudden cardiac death [3 years]
Percentage of patients that have sudden cardiac death
Aborted sudden cardiac death [3 years]
Percentage of patients that have aborted sudden cardiac death
Appropriate ICD Therapy [3 years]
Percentage of patients that have appropriate ICD therapy
Inappropriate ICD Therapy [3 years]
Percentage of patients that have inappropriate ICD therapy
Significant ventricular arrhythmias [3 years]
Percentage of patients that have significant ventricular arrhythmias
NYHA Status [3 years]
Percentage of patients in each category
Heart failure hospitalisations [3 years]
Number of events
Cardiac hospitalisations [3 years]
Number of events
Procedures related to implanted device [3 years]
Number of events
Percentage of patients alive [At 5 and 10 years]
Mortality

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

A diagnosis of NICM on contrast-enhanced cardiovascular magnetic resonance imaging
LV scar on routine CMR (patient without scar can enter the registry)
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)
Able and willing to provide informed consent

Exclusion Criteria:

New York Heart Association (NYHA) HF functional class IV after 3 months of optimal medical therapy (OMT)
Acute decompensated heart failure
Previous implantable device in situ (PPM, Cardiac Resynchronisation Therapy (CRT) or ICD)
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)
Known diagnosis of amyloidosis, sarcoidosis, arrhythmogenic right ventricular cardiomyopathy, or hypertrophic cardiomyopathy (diseases in which there are specific guidelines regarding defibrillator therapy)
Known Lamin gene mutation or a positive family history of a Lamin gene mutation
Valve disease is considered likely to require surgery during the 3 years follow-up period
Complex congenital heart disease
Any secondary prevention ICD indication
Heart transplant recipient or admitted for cardiac transplantation/ left ventricular assist device
Clinically apparent myocardial ischemia which requires revascularization
Intracardiac mass which requires surgery
Active endocarditis
Active Septicaemia
Pregnancy
Life expectancy <2 years secondary to any other cause (i.e. malignancy)
Active treatment with chemotherapy
Severe renal failure (GFR <30)
Actively participating in another study without prior agreement between both Chief Investigators