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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Device: Implantable Cardioverter-Defibrillator (ICD) or Cardiac Resynchronisation Therapy Defibrillator (CRTD)

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 Type: Interventional
• Enrollment (Estimated): 2504
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zina Eminton; Phone Number: 023 8026 8125; Email: Z.B.Eminton@soton.ac.uk
• Study Contact Backup: Name: Zoe Nicholas; Phone Number: 023 8120 8538; Email: zoe.nicholas@uhs.nhs.uk

Study Locations

• United Kingdom
  • Exeter, United Kingdom, EX2 5DW
    • Recruiting
    • Royal Devon & Exeter Hospital
    • Contact: Andrew Ludman, Dr; Phone Number: 01392 411611
  • London, United Kingdom, EC1A 7BE
    • Recruiting
    • St Bartholomew's Hospital
    • Contact: Kostas Savvatis; Phone Number: 0207 3777 000
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • King's College Hospital
    • Contact: Daniel Sado, Dr; Phone Number: 020 3299 9000
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guy's Hospital
    • Contact: Anoop Shetty; Phone Number: 020 7188 7188
  • Swansea, United Kingdom, SA6 6NL
    • Recruiting
    • Morriston Hospital
    • Contact: Geraint Jenkins; Phone Number: 01792 702222
  • Buckinghamshire
    • High Wycombe, Buckinghamshire, United Kingdom, HP11 2TT
      • Recruiting
      • Wycombe Hospital
      • Contact: Norman Qureshi, Dr; Phone Number: 01494 425958
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8DH
      • Recruiting
      • Derriford Hospital
      • Contact: Ben Sieniewicz, Dr; Phone Number: 01752 202082
  • Dorset
    • Bournemouth, Dorset, United Kingdom, BH7 7DW
      • Recruiting
      • Royal Bournemouth Hospital
      • Contact: Chris Critoph; Phone Number: 01202 303626
  • Essex
    • Basildon, Essex, United Kingdom, SS16 5NL
      • Recruiting
      • Essex Cardiothoracic Centre
      • Contact: Jason Dungu; Phone Number: 01268 524900
  • Great Yarmouth
    • Gorleston-on-Sea, Great Yarmouth, United Kingdom, NR31 6LA
      • Recruiting
      • James Paget University Hospitals NHS FT
      • Contact: Sunil Nair, Dr; Phone Number: 01493 452452
  • Hampshire
    • Portsmouth, Hampshire, United Kingdom, PO6 3LY
      • Recruiting
      • Portsmouth Hospitals University NHS Trust
      • Contact: Geraint Morton; Phone Number: 02392286000
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Recruiting
      • University Hospital Southampton Nhs Foundation Trust
      • Contact: Andrew Flett; Phone Number: +44 (0)23 8120 8538; Email: andrew.flett@uhs.nhs.uk
      • Contact: Zoe Nicholas; Phone Number: +44 (0)23 8120 8538; Email: zoe.nicholas@uhs.nhs.uk
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Not yet recruiting
      • Southampton Clinical Trials Unit
      • Contact: Zina Eminton; Phone Number: 023 8026 8125; Email: Z.B.Eminton@soton.ac.uk
      • Contact: Jacqui Nuttall; Phone Number: 023 8120 3866; Email: J.Nuttall@soton.ac.uk
      • Principal Investigator: Andrew Flett, BSc, MBBS, FRCP, MD(Res)
      • Principal Investigator: Nick Curzen, BM(Hons) PhD FRCP
  • Kent
    • Canterbury, Kent, United Kingdom, CT1 3NG
      • Recruiting
      • Kent & Canterbury Hospital
      • Contact: Steven White; Phone Number: 01227 766877
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY3 8NR
      • Recruiting
      • Blackpool Victoria Hospiatal
      • Contact: Alison Seed, Dr; Phone Number: 01253 300000
    • Liverpool, Lancashire, United Kingdom, L14 3PE
      • Recruiting
      • Liverpool Heart & Chest
      • Contact: Archie Rao; Phone Number: 0151 600 1616
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE3 9QP
      • Recruiting
      • Glenfield Hospital
      • Contact: Gerry McCann; Phone Number: 01268 524900
  • London
    • Tooting, London, United Kingdom, SW17 0QT
      • Recruiting
      • St George's Hospital
      • Contact: Fadi Jouhra, Dr; Phone Number: 02086721255
  • North Yorkshire
    • Middlesbrough, North Yorkshire, United Kingdom, TS4 3BW
      • Recruiting
      • The James Cook University Hospital
      • Contact: Andrew Turley, Dr; Phone Number: 01642 850850
  • Northumbria
    • Ashington, Northumbria, United Kingdom, NE63 9JJ
      • Active, not recruiting
      • Wansbeck General Hospital
  • Nortrh Yorkshire
    • Scarborough, Nortrh Yorkshire, United Kingdom, YO12 6QL
      • Recruiting
      • Scarborough Hospital
      • Contact: Daniel Swarbrick, Dr; Phone Number: 01723 368111
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Recruiting
      • Nottingham City Hospital
      • Contact: Jenny Chuen, Dr; Phone Number: 0115 969 1169
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Recruiting
      • The John Radcliffe Hospital
      • Contact: Julian Ormerod, Dr; Phone Number: 0300 304 7777
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZN
      • Recruiting
      • Aberdeen Royal Infirmary
      • Contact: Dana Dawson; Phone Number: 03454566000
    • Edinburgh, Scotland, United Kingdom, EH16 4SA
      • Recruiting
      • Royal Infirmary of Edinburgh
      • Contact: Marc Dweck; Phone Number: 0131 536 1000
  • Somerset
    • Taunton, Somerset, United Kingdom, TA1 5DA
      • Recruiting
      • Musgrove Park Hospital
      • Contact: Guy Furniss, Dr; Phone Number: 01823 333444
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S5 7AU
      • Recruiting
      • Northern General Hospital
      • Contact: Dominic Rogers, Dr; Phone Number: 0114 243 4343
  • Stockton-on-Tees
    • Hardwick, Stockton-on-Tees, United Kingdom, TS19 8PE
      • Recruiting
      • University Hospital of North Tees
      • Contact: Matthew Dewhurst, Dr; Phone Number: 01642 617617
  • Surrey
    • Camberley, Surrey, United Kingdom, GU16 7UJ
      • Recruiting
      • Frimley Park Hospital
      • Contact: Andrew Cox, Dr; Phone Number: 0300 614 5000
    • Redhill, Surrey, United Kingdom, RH1 5RH
      • Recruiting
      • Surrey & Sussex Healthcare NHS Trust
      • Contact: Cheuk Chan, Dr; Phone Number: 01737 768511
  • West Midlands
    • Wolverhampton, West Midlands, United Kingdom, WV10 0QP
      • Recruiting
      • New Cross Hospital
      • Contact: Anita Arya; Phone Number: 01902 307999
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS1 3EX
      • Recruiting
      • Leeds General Infirmary
      • Contact: John Greenwood; Phone Number: 01132432799
    • Wakefield, West Yorkshire, United Kingdom, WF1 4DG
      • Recruiting
      • Pinderfields Hospital
      • Contact: Peter Swaboda; Phone Number: 01924 541000
  • Worcestershire
    • Worcester, Worcestershire, United Kingdom, WR5 1DD
      • Recruiting
      • Worcestershire Royal Hospital
      • Contact: David Wilson, Dr; Phone Number: 01905 763333

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients alive	All-cause mortality	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Cardiovascular Death	Percentage of patients that have cardiovascular death	3 years
Sudden cardiac death	Percentage of patients that have sudden cardiac death	3 years
Aborted sudden cardiac death	Percentage of patients that have aborted sudden cardiac death	3 years
Appropriate ICD Therapy	Percentage of patients that have appropriate ICD therapy	3 years
Inappropriate ICD Therapy	Percentage of patients that have inappropriate ICD therapy	3 years
Significant ventricular arrhythmias	Percentage of patients that have significant ventricular arrhythmias	3 years
NYHA Status	Percentage of patients in each category	3 years
Heart failure hospitalisations	Number of events	3 years
Cardiac hospitalisations	Number of events	3 years
Procedures related to implanted device	Number of events	3 years
Percentage of patients alive	Mortality	At 5 and 10 years

Collaborators and Investigators

• Sponsor: University Hospital Southampton NHS Foundation Trust
• Collaborators: University of Southampton; British Heart Foundation
• Investigators: Study Chair: Andrew Flett, University Hospital Southampton Nhs Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2023
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2036

Study Registration Dates

• First Submitted: September 27, 2022
• First Submitted That Met QC Criteria: September 30, 2022
• First Posted (Actual): October 5, 2022

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Implantable Loop Recorder; Left ventricular ejection fraction (LVEF); Cardiac Magnetic Resonance Imaging (CMR); Implantable Cardioverter Device; Myocardial scar
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Cardiomyopathies; Heart Failure, Systolic
• Other Study ID Numbers: RHMCAR0581

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No