Therapy to Maintain Remission in Dilated Cardiomyopathy

NCT06091475 | Recruiting DMC

• 1 other identifier: 22HH8010
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

One third of patients diagnosed with heart failure demonstrate left ventricular reverse remodelling and recovery of cardiac function following a period of medical therapy. The TRED-HF trial investigated the impact of therapy withdrawal in this cohort and found that 40% of patients relapsed within 6 months of stopping treatment. In this follow-on study, the investigators will investigate the safety of therapy withdrawal of sodium cotransporter 2 inhibitors (SGLT2i) and mineralocorticord receptor anatagonists (MRAs) in patients with a previous diagnosis of heart failure and recovered cardiac function, in a randomised controlled trial to assess whether this maintains remission in this population.

Conditions

Heart Failure; Cardiomyopathy, Dilated; Cardiomyopathies; Heart Diseases

Keywords

Cardiomyopathy; heart failure

Outcome Measures

Primary Outcomes (4)

• Heart Failure Relapse assessed through left ventricular ejection fraction (LVEF)

  Relapse of DCM defined by a reduction in LVEF\>10% and to below 50%

  32 weeks

• Heart Failure Relapse assessed through pro-BNP

  Relapse of DCM defined by a two-fold rise in NT-pro-BNP and to \>400ng/L

  32 weeks

• Number of patients with heart failure Relapse assessed through signs of heart failure

  Relapse of DCM defined by clinical signs of heart failure as determined by the research team

  32 weeks

• Number of patients with heart failure Relapse assessed through symptoms of heart failure

  Relapse of DCM defined by clinical symptoms of heart failure as determined by the research team

  32 weeks

Secondary Outcomes (9)

• Left ventricular ejection fraction (LVEF)

  32 weeks

• Left Ventricular End-Diastolic Volume Index indexed to body surface area (ml/m2) (LVEDVi)

  32 weeks

• left ventricular global longitudinal strain (LV GLS)

  32 weeks

• left ventricular mass index (LVMi; g/m2)

  32 weeks

• left atrial volume index (LAVi; ml/m2)

  32 weeks

Study Arms (2)

Withdrawal of treatment with eplerenone or spironolactone, and empagliflozin and dapalgiflozin

EXPERIMENTAL

Gradual, supervised withdrawal of ineralocorticoid receptor antagonists (spironolactone or eplerenone) and sodium glucose cotransporter 2 inhibitor (dapagliflozin or empagliflozin) over 4-16 weeks. Continued monitoring off study therapies during the cross-over phase.

Drug: Other

Continued treatment with eplerenone or spironolactone, and empagliflozin and dapagliflozin

NO INTERVENTION

Continuation of usually prescribed pharmacological therapy over 16 weeks followed by cross-over to withdrawal of SGLT2i and MRA over the subsequent 4-16 weeks.

Interventions

Other DRUG

Withdrawal of mineralocorticoid receptor antagonists and/or sodium glucose cotransporter 2 inhibitors

Also known as: Withdrawal of spironolactone or eplerenone and dapagliflozin or empagliflozin

Withdrawal of treatment with eplerenone or spironolactone, and empagliflozin and dapalgiflozin

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• a diagnosis of dilated cardiomyopathy,
• previous left ventricular ejection fraction (LVEF) \<40% (on echocardiography or cardiovascular magnetic resonance \[CMR\]),
• current LVEF \>50% with normal left ventricular end-diastolic volume (LVEDV),
• plasma NT-pro-BNP\<250ng/L,
• New York Heart Association (NYHA) class I,
• sinus rhythm,
• taking a beta-blocker and an angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB) or sacubitril-valsartan, along with either a mineralocorticoid receptor antagonist (MRA) and/or sodium glucose co-transporter 2 inhibitor (SGLT2i).

You may not qualify if:

• Atrial fibrillation,
• prior sustained ventricular tachycardia or fibrillation,
• a known likely pathogenic or pathogenic variant in LMNA/DSP/FLNC/RBM20,
• sudden cardiac or heart failure death in a first degree relative \<50 years,
• contraindication to CMR,
• estimated glomerular filtration rate (eGFR) \<60mls/min,
• planned pregnancy,8) active myocardial inflammation,
• \) diabetes mellitus managed with an SGLT2i, 10) urinary albumin-to-creatine ratio of 200-5000 (mg:g) and eGFR\< 75mls/min.

Sponsors & Collaborators

• Imperial College London: lead
• Royal Brompton & Harefield NHS Foundation Trust: collaborator

Study Sites (1)

Royal Brompton Hospital

London, United Kingdom

RECRUITING

Related Publications (1)

• Halliday BP, Wassall R, Lota AS, Khalique Z, Gregson J, Newsome S, Jackson R, Rahneva T, Wage R, Smith G, Venneri L, Tayal U, Auger D, Midwinter W, Whiffin N, Rajani R, Dungu JN, Pantazis A, Cook SA, Ware JS, Baksi AJ, Pennell DJ, Rosen SD, Cowie MR, Cleland JGF, Prasad SK. Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial. Lancet. 2019 Jan 5;393(10166):61-73. doi: 10.1016/S0140-6736(18)32484-X. Epub 2018 Nov 11.

  PMID: 30429050 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Cardiomyopathy, Dilated; Cardiomyopathies; Heart Diseases

Interventions

Eplerenone; dapagliflozin; empagliflozin

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Cardiomegaly; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Brian P Halliday, MBChB

  Imperial College London, Royal Brompton Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Saad Javed, MBChB

CONTACT

02073528121; tred2trial@imperial.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2023
• First Posted: October 19, 2023
• Study Start: December 2, 2023
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): September 15, 2026
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)