Clinical trial NCT05441839: UK Heart Failure With Preserved Ejection Fraction
Official title: UK Heart Failure With Preserved Ejection Fraction Registry
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Heart Failure With Preserved Ejection Fraction (HFpEF)
Lead sponsor: Manchester University NHS Foundation Trust
Sponsor class: OTHER_GOV
Collaborators: name: Pumping Marvellous Foundation
name: British Society for Heart Failure
name: NIHR National Biosample Centre
name: British Heart Foundation Data Science Centre
First posted: 2022-07-01
Enrollment: 10000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All individuals will be considered for inclusion in this study regardless of age, disability, gender reassignment, marriage and civil partnership, pregnancy and maternity, race, religion and belief, sex, and sexual orientation, except where the study inclusion and exclusion criteria explicitly state otherwise.

Brief summary: Heart failure occurs when the heart is no longer able to pump blood around the body properly. It can cause breathlessness, swollen feet and ankles, and tiredness. In about half of patients with heart failure, one measure of the heart's pumping function, called the 'ejection fraction', is normal. This type of heart failure is called heart failure with preserved ejection fraction, or HFpEF.

HFpEF remains poorly understood. It is not clear why some people develop HFpEF, or what determines the severity of the condition. Treatment options may be limited.

UK HFpEF is a study that aims to gain a better understanding of why people develop HFpEF, develop better tests to diagnosis it, identify and test new treatments, and follow the health of the people taking part over many years.

Detailed description: Approximately half of patients with heart failure have a normal, or preserved, left ventricular ejection fraction (HFpEF) (Owen et al, 2006). Rather than being a single diagnosis, it has become clear that HFpEF represents a heterogeneous syndrome involving a range of pathophysiological mechanisms, clinical factors and outcomes (Lewis et al, 2017). However, to-date, HFpEF has generally been considered as a single disease entity. Several high profile phase III trials in HFpEF have shown potentially impressive efficacy in some subgroups of patients, but failed to prove significance over entire cohorts (Pitt et al, 2014) (Solomon et al, 2019). This is likely due to the 'one-size-fits-all' approach taken, with insufficient stratification of the various underlying disease mechanisms.

The large and rapidly growing burden that HFpEF places on our healthcare systems mean there is a pressing need to better understand HFpEF and improve the management of patients with it. The recurrent lack of benefit of the one-size-fits-all approach mandates a new, personalised approach.

The UK HFpEF registry will be a key platform for collaborative UK clinical and translational HFpEF research. The aim is that multiple centres will collaborate and contribute patients such that the registry will provide deep phenotyping, linked to outcomes, in, ultimately, many thousands of patients. This will enable, for example, machine learning techniques to be applied at scale in order to reclassify HFpEF more powerfully. It will provide a platform for the development of diagnostics specific to the different HFpEF subgroups, and for more effective trials that will target groups of patients in whom new, repurposed or previously discarded treatments are expected to be effective. Moreover, it will provide cohorts of patients readily available for recruitment, with linkage in place for outcomes. It could be used to leverage commercial funding and participation, facilitated by simplified, single-point access for industry. It will enable scaled investigation aimed at understanding causes of HFpEF, improving risk stratification and providing better care.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent
2. Diagnosis of HFpEF by a cardiologist with HF expertise, or a primary care physician with HF expertise, or a heart failure nurse
3. Natriuretic peptide levels measured

Exclusion Criteria:

1. LV EF \< 40% (at screening or any previous measurement)
2. Known infiltrative cardiomyopathy (e.g., amyloid, sarcoid, lymphoma, endomyocardial fibrosis)
3. Known active myocarditis, constrictive pericarditis, or cardiac tamponade
4. Known genetic hypertrophic cardiomyopathy or obstructive hypertrophic cardiomyopathy
5. Known arrhythmogenic right ventricular cardiomyopathy
6. Known severe primary valvular heart disease
7. Known idiopathic, heritable or drug-induced pulmonary arterial hypertension
8. Heart transplantation or ventricular assist device
9. Complex congenital heart disease

Primary outcomes:
measure: Identification of distinct subgroups of HFpEF
timeFrame: 10 years
measure: Improve understanding of the causes of HFpEF
timeFrame: 10 years
measure: Improve risk stratification of HFpEF
timeFrame: 10 years
Secondary outcomes:
Other outcomes:
Locations:
city: Abercynon
country: United Kingdom
facility: Cwm Taf Morgannwg University Health Board
city: Aylesbury
country: United Kingdom
facility: Buckinghamshire Healthcare NHS Trust
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Chelmsford
country: United Kingdom
facility: Broomfield Hospital
city: Dundee
country: United Kingdom
facility: NHS Tayside
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: Ipswich
country: United Kingdom
facility: West Suffolk NHS Foundation Trust
city: Kettering
country: United Kingdom
facility: Kettering General Hospital
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Foundation Trust
city: London
country: United Kingdom
facility: Barnet Hospital
city: London
country: United Kingdom
facility: Guys and St. Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation trust
city: Middlesborough
country: United Kingdom
facility: The James Cook University Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Northumbria Healthcare NHS Foundation Trust
city: Norwich
country: United Kingdom
facility: Norfolk & Norwich University Hospitals NHS Foundation Trust
city: Nuneaton
country: United Kingdom
facility: George Eliot Hospital
city: Peterborough
country: United Kingdom
facility: North West Anglia NHS Foundation Trust
city: Poole
country: United Kingdom
facility: University Hospitals Dorset NHS Foundation Trust
city: Rhyl
country: United Kingdom
facility: Betsi Cadwaldr University Health Board
city: Salisbury
country: United Kingdom
facility: Salisbury NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
city: Stockton-on-Tees
country: United Kingdom
facility: University Hospital of North Tees
city: Sunderland
country: United Kingdom
facility: South Tyneside & Sunderland NHS Foundation Trust
city: Westcliff-on-Sea
country: United Kingdom
facility: Southend University Hospital
Study officials:
affiliation: Manchester University NHS Foundation Trust
name: Chris Miller, MBChB FRCP
role: STUDY_CHAIR
References:
citation: Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 Jul 20;355(3):251-9. doi: 10.1056/NEJMoa052256.
citation: Lewis GA, Schelbert EB, Williams SG, Cunnington C, Ahmed F, McDonagh TA, Miller CA. Biological Phenotypes of Heart Failure With Preserved Ejection Fraction. J Am Coll Cardiol. 2017 Oct 24;70(17):2186-2200. doi: 10.1016/j.jacc.2017.09.006.
citation: Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Harty B, Heitner JF, Kenwood CT, Lewis EF, O'Meara E, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, Yang S, McKinlay SM; TOPCAT Investigators. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014 Apr 10;370(15):1383-92. doi: 10.1056/NEJMoa1313731.
citation: Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Desai AS, Claggett B, Jhund PS, Boytsov SA, Comin-Colet J, Cleland J, Dungen HD, Goncalvesova E, Katova T, Kerr Saraiva JF, Lelonek M, Merkely B, Senni M, Shah SJ, Zhou J, Rizkala AR, Gong J, Shi VC, Lefkowitz MP; PARAGON-HF Investigators and Committees. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2019 Oct 24;381(17):1609-1620. doi: 10.1056/NEJMoa1908655. Epub 2019 Sep 1.