UK Heart Failure With Preserved Ejection Fraction

Heart Failure With Preserved Ejection Fraction (HFpEF) Clinical Trial

— UK HFpEF  

Official title:

UK Heart Failure With Preserved Ejection Fraction Registry

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05441839
• Other study ID #: B01434
• Status: Recruiting
• Start date: October 7, 2022
• Est. completion date: June 2037

Study information

• Verified date: October 2022
• Source: Manchester University NHS Foundation Trust
• Contact: Fardad Soltani, MBChB MRCP
• Phone: 0161 291 3223
• Email: fardad.soltani[@]mft.nhs.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10000
• Est. completion date: June 2037
• Est. primary completion date: June 2037
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction (HFpEF)

Locations

Country	Name	City	State
United Kingdom	Manchester University NHS Foundation trust	Manchester

Sponsors (10)

Lead Sponsor	Collaborator
Manchester University NHS Foundation Trust	British Heart Foundation Data Science Centre, British Society for Heart Failure, NIHR National Biosample Centre, Pumping Marvellous Foundation, Salisbury NHS Foundation Trust, Sheffield Teaching Hospitals NHS Foundation Trust, University College, London, University of Glasgow, University of Leicester

Country where clinical trial is conducted

United Kingdom, 

References & Publications (4)

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. Review. — View 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. — View 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. — View 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, Düngen 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of distinct subgroups of HFpEF	Identify distinct subgroups of HFpEF based on disease mechanisms, clinical factors and outcomes	10 years
Primary	Improve understanding of the causes of HFpEF	Improve the understanding of the cause of HFpEF to provide the basis for developing and evaluating new therapies and diagnostics	10 years
Primary	Improve risk stratification of HFpEF	Identify and improve risk stratification models for HFpEF patients	10 years