Therapy to Maintain Remission in Dilated Cardiomyopathy

Heart Failure Clinical Trial

— TRED-HF2  

Official title:

A Randomised Trial Examining Therapy to Maintain Remission in Dilated Cardiomyopathy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06091475
• Other study ID #: 22HH8010
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 20, 2023
• Est. completion date: September 15, 2026

Study information

• Verified date: October 2023
• Source: Imperial College London
• Contact: Saad Javed, MBChB
• Phone: 02073528121
• Email: tred2trial[@]imperial.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: September 15, 2026
• Est. primary completion date: August 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Heart Diseases
• Heart Failure

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Imperial College London	Royal Brompton & Harefield NHS Foundation Trust

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	Left ventricular ejection fraction (LVEF)	Change in LVEF between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)	32 weeks
Secondary	Left Ventricular End-Diastolic Volume Index indexed to body surface area (ml/m2) (LVEDVi)	Change in LVEDVi between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)	32 weeks
Secondary	left ventricular global longitudinal strain (LV GLS)	Change in LV GLS between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)	32 weeks
Secondary	left ventricular mass index (LVMi; g/m2)	Change in LVMI between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)	32 weeks
Secondary	left atrial volume index (LAVi; ml/m2)	Change in LAVi between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)	32 weeks
Secondary	left atrial strain (LAS)	Change in LAS between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)	32 weeks
Secondary	right ventricular ejection fraction (RVEF; %)	Change in RVEF between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)	32 weeks
Secondary	Change in Quality of Life (EQ-5D-5L score)	Assessed through EQ-5D-5L score. This is a validated score from the EuroQoL research foundation, graded from 5 to 25 with a higher score reflecting a worse quality of life	32 weeks
Secondary	Change in Quality of Life (Treatment Burden Questionnaire score)	Assessed through TBQ (Treatment Burden Questionnaire) score. The TBQ score is graded from 0 to 150 with a higher score reflecting a greater treatment burden	32 weeks