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

Heart Failure Clinical Trial

— BRITISH  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05568069
• Other study ID #: RHMCAR0581
• Status: Recruiting
• Phase: N/A
• Start date: April 12, 2023
• Est. completion date: April 1, 2036

Study information

• Verified date: May 2024
• Source: University Hospital Southampton NHS Foundation Trust
• Contact: Zina Eminton
• Phone: 023 8026 8125
• Email: z.b.eminton[@]soton.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2504
• Est. completion date: April 1, 2036
• Est. primary completion date: April 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiomyopathies
• Heart Failure
• Heart Failure, Systolic

Intervention

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.

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Wansbeck General Hospital	Ashington	Northumbria
United Kingdom	Essex Cardiothoracic Centre	Basildon	Essex
United Kingdom	Blackpool Victoria Hospiatal	Blackpool	Lancashire
United Kingdom	Royal Bournemouth Hospital	Bournemouth	Dorset
United Kingdom	Frimley Park Hospital	Camberley	Surrey
United Kingdom	Kent & Canterbury Hospital	Canterbury	Kent
United Kingdom	Durham & Darlington NHS Foundation Trust	Darlington	Durham
United Kingdom	Royal Infirmary of Edinburgh	Edinburgh	Scotland
United Kingdom	Royal Devon & Exeter Hospital	Exeter
United Kingdom	James Paget University Hospitals NHS FT	Gorleston-on-Sea	Great Yarmouth
United Kingdom	University Hospital of North Tees	Hardwick	Stockton-on-Tees
United Kingdom	Wycombe Hospital	High Wycombe	Buckinghamshire
United Kingdom	Leeds General Infirmary	Leeds	West Yorkshire
United Kingdom	Glenfield Hospital	Leicester	Leicestershire
United Kingdom	Liverpool Heart & Chest	Liverpool	Lancashire
United Kingdom	Guy's Hospital	London
United Kingdom	King's College Hospital	London
United Kingdom	Royal Brompton Hospital	London
United Kingdom	St Bartholomew's Hospital	London
United Kingdom	The James Cook University Hospital	Middlesbrough	North Yorkshire
United Kingdom	Newcastle Freeman Hospital	Newcastle	Newcastle Upon Tyne
United Kingdom	Nottingham City Hospital	Nottingham	Nottinghamshire
United Kingdom	The John Radcliffe Hospital	Oxford	Oxfordshire
United Kingdom	Derriford Hospital	Plymouth	Devon
United Kingdom	Portsmouth Hospitals University NHS Trust	Portsmouth	Hampshire
United Kingdom	Surrey & Sussex Healthcare NHS Trust	Redhill	Surrey
United Kingdom	Scarborough Hospital	Scarborough	Nortrh Yorkshire
United Kingdom	Northern General Hospital	Sheffield	South Yorkshire
United Kingdom	Southampton Clinical Trials Unit	Southampton	Hampshire
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton	Hampshire
United Kingdom	Morriston Hospital	Swansea
United Kingdom	Musgrove Park Hospital	Taunton	Somerset
United Kingdom	St George's Hospital	Tooting	London
United Kingdom	Pinderfields Hospital	Wakefield	West Yorkshire
United Kingdom	New Cross Hospital	Wolverhampton	West Midlands
United Kingdom	Worcestershire Royal Hospital	Worcester	Worcestershire

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital Southampton NHS Foundation Trust	British Heart Foundation, University of Southampton

Country where clinical trial is conducted

United Kingdom, 

Outcome

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