Clinical trial NCT06091475: Therapy to Maintain Remission in Dilated Cardiomyopathy
Official title: A Randomised Trial Examining Therapy to Maintain Remission in Dilated Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Cardiomyopathy, Dilated
Cardiomyopathies
Heart Diseases
Keywords: Cardiomyopathy
heart failure
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Royal Brompton & Harefield NHS Foundation Trust
First posted: 2023-10-19
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Heart Failure Relapse assessed through left ventricular ejection fraction (LVEF)
timeFrame: 32 weeks
measure: Heart Failure Relapse assessed through pro-BNP
timeFrame: 32 weeks
measure: Number of patients with heart failure Relapse assessed through signs of heart failure
timeFrame: 32 weeks
measure: Number of patients with heart failure Relapse assessed through symptoms of heart failure
timeFrame: 32 weeks
Secondary outcomes:
measure: Left ventricular ejection fraction (LVEF)
timeFrame: 32 weeks
measure: Left Ventricular End-Diastolic Volume Index indexed to body surface area (ml/m2) (LVEDVi)
timeFrame: 32 weeks
measure: left ventricular global longitudinal strain (LV GLS)
timeFrame: 32 weeks
measure: left ventricular mass index (LVMi; g/m2)
timeFrame: 32 weeks
measure: left atrial volume index (LAVi; ml/m2)
timeFrame: 32 weeks
measure: left atrial strain (LAS)
timeFrame: 32 weeks
measure: right ventricular ejection fraction (RVEF; %)
timeFrame: 32 weeks
measure: Change in Quality of Life (EQ-5D-5L score)
timeFrame: 32 weeks
measure: Change in Quality of Life (Treatment Burden Questionnaire score)
timeFrame: 32 weeks
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Brompton Hospital
Study officials:
affiliation: Imperial College London, Royal Brompton Hospital
name: Brian P Halliday, MBChB
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.