Therapy to Maintain Remission in Dilated Cardiomyopathy (TRED-HF2)

October 17, 2023 updated by: Imperial College London

A Randomised Trial Examining Therapy to Maintain Remission in Dilated Cardiomyopathy

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Other
Withdrawal of mineralocorticoid receptor antagonists and/or sodium glucose cotransporter 2 inhibitors
Other Names:
  • Withdrawal of spironolactone or eplerenone and dapagliflozin or empagliflozin
No Intervention: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Heart Failure Relapse assessed through left ventricular ejection fraction (LVEF)
Time Frame: 32 weeks
Relapse of DCM defined by a reduction in LVEF>10% and to below 50%
32 weeks
Heart Failure Relapse assessed through pro-BNP
Time Frame: 32 weeks
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
Time Frame: 32 weeks
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
Time Frame: 32 weeks
Relapse of DCM defined by clinical symptoms of heart failure as determined by the research team
32 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Left ventricular ejection fraction (LVEF)
Time Frame: 32 weeks
Change in LVEF between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)
32 weeks
Left Ventricular End-Diastolic Volume Index indexed to body surface area (ml/m2) (LVEDVi)
Time Frame: 32 weeks
Change in LVEDVi between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)
32 weeks
left ventricular global longitudinal strain (LV GLS)
Time Frame: 32 weeks
Change in LV GLS between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)
32 weeks
left ventricular mass index (LVMi; g/m2)
Time Frame: 32 weeks
Change in LVMI between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)
32 weeks
left atrial volume index (LAVi; ml/m2)
Time Frame: 32 weeks
Change in LAVi between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)
32 weeks
left atrial strain (LAS)
Time Frame: 32 weeks
Change in LAS between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)
32 weeks
right ventricular ejection fraction (RVEF; %)
Time Frame: 32 weeks
Change in RVEF between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)
32 weeks
Change in Quality of Life (EQ-5D-5L score)
Time Frame: 32 weeks
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
Change in Quality of Life (Treatment Burden Questionnaire score)
Time Frame: 32 weeks
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Imperial College London

Collaborators

Royal Brompton & Harefield NHS Foundation Trust

Investigators

  • Principal Investigator: Brian P Halliday, MBChB, Imperial College London, Royal Brompton Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 20, 2023

Primary Completion (Estimated)

August 15, 2026

Study Completion (Estimated)

September 15, 2026

Study Registration Dates

First Submitted

August 16, 2023

First Submitted That Met QC Criteria

October 17, 2023

First Posted (Actual)

October 19, 2023

Study Record Updates

Last Update Posted (Actual)

October 19, 2023

Last Update Submitted That Met QC Criteria

October 17, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22HH8010

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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