Heart FailureTRED-HF2NCT06091475
Therapy to Maintain Remission in Dilated Cardiomyopathy
A study testing Other in people with Heart Failure and Cardiomyopathy, Dilated, run by Imperial College London at 1 site in United Kingdom.
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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Heart Failure, Cardiomyopathy, Dilated, Cardiomyopathies
- What is being tested?
- Other
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 2 Dec 2023to 15 Sep 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Royal Brompton Hospital
London
Saad Javed, tred2trial@imperial.ac.uk
About this study
Official title: 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.
Read the 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.
- Being tested
- Other
- Keywords
- Cardiomyopathy, heart failure
- Medical subject headings
- Heart Failure, Cardiomyopathy, Dilated, Cardiomyopathies, Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OtherDrug
Also called Withdrawal of spironolactone or eplerenone and dapagliflozin or empagliflozin
Withdrawal of mineralocorticoid receptor antagonists and/or sodium glucose cotransporter 2 inhibitors
| Study group | Role | What they receive |
|---|---|---|
| Withdrawal of treatment with eplerenone or spironolactone, and empagliflozin and dapalgiflozin | Experimental | 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. Receives: Drug: Other |
| Continued treatment with eplerenone or spironolactone, and empagliflozin and dapagliflozin | No intervention | 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 being measured
The primary outcome is the main question the study is designed to answer.
Heart Failure Relapse assessed through left ventricular ejection fraction (LVEF)
Relapse of DCM defined by a reduction in LVEF>10% and to below 50%
Measured: 32 weeks
Heart Failure Relapse assessed through pro-BNP
Relapse of DCM defined by a two-fold rise in NT-pro-BNP and to >400ng/L
Measured: 32 weeks
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
Measured: 32 weeks
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
Measured: 32 weeks
Secondary outcomes (9)
Left ventricular ejection fraction (LVEF)
Change in LVEF between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)
Measured: 32 weeks
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)
Measured: 32 weeks
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)
Measured: 32 weeks
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)
Measured: 32 weeks
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)
Measured: 32 weeks
left atrial strain (LAS)
Change in LAS between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)
Measured: 32 weeks
right ventricular ejection fraction (RVEF; %)
Change in RVEF between baseline, during randomised phase (0-16 weeks) and follow-on phase (16-32 weeks)
Measured: 32 weeks
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
Measured: 32 weeks
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
Measured: 32 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2023
- Study start2 Dec 2023
- Primary completion15 Aug 2026 (estimated)
- Study completion15 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Royal Brompton & Harefield NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Brian P Halliday, MBChB, Principal investigator, Imperial College London, Royal Brompton Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06091475
- Sponsor's protocol ID
- 22HH8010
- Acronym
- TRED-HF2
- Status last verified
- Sep 2024
- First submitted
- 16 Aug 2023
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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 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.
PubMed 30429050
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Trial Examining Therapy to Maintain Remission in Dilated Cardiomyopathy
- ClinicalTrials.gov ID
- NCT06091475
- Acronym / sponsor ID
- TRED-HF2 / 22HH8010
- Keywords
- Cardiomyopathy, heart failure
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Royal Brompton & Harefield NHS Foundation Trust
- Study start
- 2 Dec 2023 (actual)
- Primary completion
- 15 Aug 2026 (estimated)
- Study completion
- 15 Sep 2026 (estimated)
- First posted
- 19 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Withdrawal of treatment with eplerenone or spironolactone, and empagliflozin and dapalgiflozin | Experimental | Drug: OtherGradual, 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. |
| Continued treatment with eplerenone or spironolactone, and empagliflozin and dapagliflozin | No intervention | –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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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,
Key exclusion criteria (8 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OtherAlso: Withdrawal of spironolactone or eplerenone and dapagliflozin or empagliflozinWithdrawal of mineralocorticoid receptor antagonists and/or sodium glucose cotransporter 2 inhibitors | Drug | Withdrawal of treatment with eplerenone or spironolactone, and empagliflozin and dapalgiflozin |
Primary outcome
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%
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
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
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
9 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Background: PubMed 30429050Halliday 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian P Halliday, MBChB principal investigator
Imperial College London, Royal Brompton Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Other in people with Heart Failure and Cardiomyopathy, Dilated, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Saad Javed, MBChB (02073528121, tred2trial@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heart Failure Relapse assessed through left ventricular ejection fraction (LVEF) (time frame: 32 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06091475, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.