Therapy to Maintain Remission in Dilated Cardiomyopathy

NCT ID: NCT06091475

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-02
• Study Completion Date: 2026-09-15

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.

Detailed Description

One third of patients diagnosed with heart failure demonstrate left ventricular reverse remodelling and recovery of cardiac function following a period of medical therapy. These patients have an excellent long-term prognosis. Whether they need to remain on long-term medical therapy is not clear. Current guideline directed treatment of patients with heart failure relies on a combination of (1) angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs), (2) beta-blockers, (3) mineralocorticoid antagonists, and (4) sodium-glucose co-transporter 2 inhibitors (SGLT2i).

The TRED-HF trial, confirmed that complete withdrawal of beta-blockers, ACEi or ARBs, and MRAs resulted in relapse within 6 months in 40% of asymptomatic patients with a previous diagnosis of DCM and improved cardiac function. This confirmed that many patients have heart failure remission rather than sustained recovery and still benefit from at least some pharmacological therapy. Defining the therapies required to maintain heart failure remission is a priority for heart failure research, taking into account the changing therapeutic needs of many millions of patients following improvement in their cardiac function. In this follow-on study to the TRED-HF trial, the investigators will carry out an open-label, randomised clinical trial examining the safety and feasibility of sequential mineralocorticoid receptor antagonist (MRA) and sodium glucose co-transporter 2 inhibitor (SGLT2i) withdrawal in 50 patients with dilated cardiomyopathy who are now in heart failure remission and taking angiotensin system inhibitors and beta-blockers. Patients will have serial cardiovascular magnetic resonance (CMR) scans and circulating biomarkers after withdrawal of each therapy and will be followed for 8 months. The primary end-point will be relapse of heart failure defined by features of adverse remodelling.

Conditions

Heart Failure; Cardiomyopathy, Dilated; Cardiomyopathies; Heart Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Other

Intervention Type: DRUG

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

Continued treatment with eplerenone or spironolactone, and empagliflozin and dapagliflozin

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Other

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

Intervention Type: DRUG

Other Intervention Names

Withdrawal of spironolactone or eplerenone and dapagliflozin or empagliflozin

Eligibility Criteria

Inclusion Criteria

1. a diagnosis of dilated cardiomyopathy,

2. previous left ventricular ejection fraction (LVEF) <40% (on echocardiography or cardiovascular magnetic resonance [CMR]),

3. current LVEF >50% with normal left ventricular end-diastolic volume (LVEDV),

4. plasma NT-pro-BNP<250ng/L,

5. New York Heart Association (NYHA) class I,

6. sinus rhythm,

7. 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).

Exclusion Criteria

1. Atrial fibrillation,

2. prior sustained ventricular tachycardia or fibrillation,

3. a known likely pathogenic or pathogenic variant in LMNA/DSP/FLNC/RBM20,

4. sudden cardiac or heart failure death in a first degree relative <50 years,

5. contraindication to CMR,

6. estimated glomerular filtration rate (eGFR) <60mls/min,

7. planned pregnancy,8) active myocardial inflammation,

9) diabetes mellitus managed with an SGLT2i, 10) urinary albumin-to-creatine ratio of 200-5000 (mg:g) and eGFR< 75mls/min.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Royal Brompton & Harefield NHS Foundation Trust

OTHER

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brian P Halliday, MBChB

Role: PRINCIPAL_INVESTIGATOR

Imperial College London, Royal Brompton Hospital

Locations

Royal Brompton Hospital

London, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Saad Javed, MBChB

Role: CONTACT

tred2trial@imperial.ac.uk

02073528121

Facility Contacts

Saad Javed

Role: primary

tred2trial@imperial.ac.uk

References

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.

Reference Type: BACKGROUND

PMID: 30429050 (View on PubMed)

Other Identifiers

22HH8010

Identifier Type: -

Identifier Source: org_study_id