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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Percentage of patients alive [Time frame: 3 years]

Secondary outcome measures (12)

• Change in health-related quality of life measured using KCCQ-12 [Time frame: 3 years]
• Change in health-related quality of life measured using EQ-5D-5L [Time frame: 3 years]
• Cardiovascular Death [Time frame: 3 years]
• Sudden cardiac death [Time frame: 3 years]
• Aborted sudden cardiac death [Time frame: 3 years]
• Appropriate ICD Therapy [Time frame: 3 years]
• Inappropriate ICD Therapy [Time frame: 3 years]
• Significant ventricular arrhythmias [Time frame: 3 years]
• NYHA Status [Time frame: 3 years]
• Heart failure hospitalisations [Time frame: 3 years]
• Cardiac hospitalisations [Time frame: 3 years]
• Procedures related to implanted device [Time frame: 3 years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United Kingdom · 47 centers

• Wycombe Hospital — High Wycombe
• Derriford Hospital — Plymouth
• Royal Bournemouth Hospital — Bournemouth
• Durham & Darlington NHS Foundation Trust — Darlington
• Royal Sussex County Hospital — Brighton
• Essex Cardiothoracic Centre — Basildon
• James Paget University Hospitals NHS FT — Gorleston-on-Sea
• Portsmouth Hospitals University NHS Trust — Portsmouth
• … and 39 more centers

Identifiers

NCT: NCT05568069 · RHMCAR0581

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗