Therapy to Maintain Remission in Dilated Cardiomyopathy

Official title

A Randomised Trial Examining Therapy to Maintain Remission in Dilated Cardiomyopathy

Overview

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.

Interventions

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

Primary outcome measures

• Heart Failure Relapse assessed through left ventricular ejection fraction (LVEF) [Time frame: 32 weeks]
• Heart Failure Relapse assessed through pro-BNP [Time frame: 32 weeks]
• Number of patients with heart failure Relapse assessed through signs of heart failure [Time frame: 32 weeks]
• Number of patients with heart failure Relapse assessed through symptoms of heart failure [Time frame: 32 weeks]

Secondary outcome measures (9)

• Left ventricular ejection fraction (LVEF) [Time frame: 32 weeks]
• Left Ventricular End-Diastolic Volume Index indexed to body surface area (ml/m2) (LVEDVi) [Time frame: 32 weeks]
• left ventricular global longitudinal strain (LV GLS) [Time frame: 32 weeks]
• left ventricular mass index (LVMi; g/m2) [Time frame: 32 weeks]
• left atrial volume index (LAVi; ml/m2) [Time frame: 32 weeks]
• left atrial strain (LAS) [Time frame: 32 weeks]
• right ventricular ejection fraction (RVEF; %) [Time frame: 32 weeks]
• Change in Quality of Life (EQ-5D-5L score) [Time frame: 32 weeks]
• Change in Quality of Life (Treatment Burden Questionnaire score) [Time frame: 32 weeks]

Eligibility criteria

Inclusion criteria

• 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).

Exclusion criteria

• 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,

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

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

Crossover

Masking

Open label

Primary purpose

Treatment

Study locations

United Kingdom · 1 center

• Royal Brompton Hospital — London

Publications

• 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 ope PMID 30429050

Identifiers

NCT: NCT06091475 · 22HH8010

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗