Clinical trial NCT02859311: A Pilot Feasibility Study in Recovered Heart Failure
Official title: A Pilot Feasibility Study in Recovered Heart Failure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Heart Failure
Keywords: Recovery
Lead sponsor: Royal Brompton & Harefield NHS Foundation Trust
Sponsor class: OTHER
First posted: 2016-08-09
Enrollment: 50
Sex: ALL
Minimum age (years): 16
Maximum age (years): 85
Standard ages: CHILD
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. These patients have an excellent long-term prognosis. Whether they need to remain on long-term medical therapy is not clear. The investigators will investigate the safety of therapy withdrawal in patients with a previous diagnosis of heart failure and recovered cardiac function, in a randomised controlled trial.

Detailed description: Patients with a previous diagnosis of heart failure, who have recovered cardiac function, without symptoms, normal serum biomarker concentrations and who are currently still taking heart failure medications, will be recruited. Participants will be randomised to withdrawal of therapy and control arms and will undergo imaging investigations and cardiopulmonary exercise tests at baseline along with serum biomarker tests. Those participants randomised to withdrawal of therapy will have a gradual, supervised reduction of medications. If, at anytime, there are signs of recurring heart failure, medications will be restarted. Participants in the control arm will continue their medical therapy as usual.

Participants will be followed up with further biomarker testing, cardiopulmonary exercise testing and imaging investigations at 6 months.

The primary end-point will be a relapse in heart failure, defined by adverse remodelling, increase in left ventricular size, rise in serum biomarkers or clinical evidence of heart failure as judged by the clinical team.

Eligibility criteria: Inclusion Criteria:

1. Have an index diagnosis of heart failure confirmed by 2 independent operators based on clinical details.
2. Be currently taking at least 1 of the following medications loop diuretic, betablocker, angiotension converting enzyme inhibitor/angiotensin receptor blocker and mineralocorticoid receptor antagonist.
3. Have demonstrated evidence of left ventricular reverse remodelling following the initial diagnosis with subsequent improvement in ejection fraction to \>50% and normalisation of left ventricular (LV) volumes.
4. Have no symptoms of heart failure (NYHA Class 1).
5. Low plasma NTproBNP.

Exclusion Criteria:

1. Uncontrolled hypertension.
2. More than moderate valvular disease.
3. Estimated glomerular filtration rate \<30mls/min.
4. Atrial/supraventricular/ventricular arrhythmia requiring beta-blockade.
5. Pregnancy.
6. Unstable angina.
7. Age \<16 years

Primary outcomes:
measure: Heart failure relapse
timeFrame: 6 months
Secondary outcomes:
measure: Cardiopulmonary exercise testing with peak oxygen consumption
timeFrame: 6 months
measure: Quality of life
timeFrame: 6 months
measure: Major adverse cardiovascular events (MACE) - safety end-point
timeFrame: 6 months
measure: Percentage of participants with new and sustained arrhythmias
timeFrame: 6 months
measure: Increase in left atrial volume as measured on cardiovascular magnetic resonance (CMR)
timeFrame: 6 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Brompton and Harefield NHS Trust
Study officials:
affiliation: Royal Brompton and Harefield NHS Foundation Trust
name: Sanjay Prasad, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Halliday BP, Vazir A, Owen R, Gregson J, Wassall R, Lota AS, Khalique Z, Tayal U, Jones RE, Hammersley D, Pantazis A, Baksi AJ, Rosen S, Pennell DJ, Cowie MR, Cleland JGF, Prasad SK. Heart Rate as a Marker of Relapse During Withdrawal of Therapy in Recovered Dilated Cardiomyopathy. JACC Heart Fail. 2021 Jul;9(7):509-517. doi: 10.1016/j.jchf.2021.03.010. Epub 2021 Jun 9.
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.