NCT02041130

Renal Denervation in Heart Failure Patients With Preserved Ejection Fraction (RESPECT-HF)

Renal Sympathectomy in Heart Failure (the RESPECT-HF Study) - a Study of Renal Denervation for Heart Failure With Preserved Ejection Fraction

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 144 (estimated)
• Sponsor: National University Hospital, Singapore · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Investigators will test a new approach to a form of heart failure (HF) with no current treatment proven to reduce death rates or hospitalisations. Over a third of HF cases have preserved ejection fraction (HFPEF) often on a background of high blood pressure (BP). These "stiff" hearts pump strongly but fill inefficiently resulting in poor exercise capacity and high death rates. Treatments that help when heart pumping action is poor are of no benefit in HFPEF. Recently a simple catheter procedure removing excess nerve signals to and from the kidneys ("renal denervation"; RDN) has been able to reduce BP in patients with high BP resistant to multi-drug treatment. Through removing excess nervous drive to the kidneys, heart and circulation this treatment has promise in HF. The investigators will compare effects of RDN and standard medical treatment on heart function, exercise capacity and quality of life in 144 patients with HFPEF

Detailed description

Rationale for Research:- Heart failure (HF) is common and lethal. It is the most common diagnosis for medical admissions over 60 years of age, carries a \>50% 5 year mortality and accounts for 1-2% of the total national health care budget. HF with preserved ejection fraction (HFPEF) includes over a third of HF cases presenting to New Zealand and Singapore Hospitals and has no treatment proven to reduce mortality or recurrent admissions. Renal denervation (RDN) has proven efficacy in refractory hypertension and its array of effects upon haemodynamic status, neurohumoral activity and renal function make it a rational candidate therapy in HFPEF. Aims:- The investigators aim to conduct a phase 2 randomized controlled trial of RDN in HFPEF to determine effects upon cardiac structure and function, exercise capacity, and quality of life. Primary Hypothesis: RDN will reduce left atrial volume index (LAVi) and/or left ventricular mass index (LVMi) on cardiac magnetic resonance imaging (cMRI). Secondary Hypotheses: RDN will: 1. improve exercise capacity and functional status. 2. reduce E/e' and echocardiographic grade of diastolic dysfunction. 3. reduce circulating biomarkers of cardiac load, interstitial fibrosis and inflammation. 4. improve ventricular-vascular function. 5. improve Minnesota Living with Heart Failure (MLWHF) scores. 6. reduce the composite end-point of death or re-admission with HF. Design and Methods:- Renal denervation will be tested as a therapy for HFPEF in a multi-centre open, randomized controlled trial of bilateral renal artery denervation compared with ongoing medical management. Sample size (n=144) will be sufficient to provide 90% power to detect clinically relevant effects on the primary endpoints of change in left atrial volume and left ventricular mass over 6 months post-RDN. Secondary end-points will include assessment of exercise capacity, ventricular-vascular coupling, biomarkers (of cardiac haemodynamic load, fibrosis, inflammation and cardiomyocyte loss), quality of life and cardiovascular events. Research Impact:- Heart Failure with Preserved Ejection Fraction (HFPEF) is common, triggers recurrent hospital admissions has a high mortality and carries a high burden of health care costs. There is currently no treatment which reduces admissions or improves survival in this condition. If efficacy is proven, renal nerve denervation represents a simple, cost-effective, one time only, approach that will find rapid uptake potentially for thousands of cases.If the current proposal generates positive results (followed by positive phase 3 trials) the investigators conservatively estimate RDN may reduce both mortality and HF admissions in HFPEF by at least 30%.

Conditions

• Heart Failure

Interventions

Type	Name	Description
DEVICE	Renal Denervation

Timeline

• Start date: 2013-10-01
• Primary completion: 2015-12-01
• Completion: 2016-12-01
• First posted: 2014-01-20
• Last updated: 2015-01-16

Locations

7 sites across 3 countries: Australia, New Zealand, Singapore