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

NCT02041130 | Unknown Phase 2 DMC

• 1 other identifier: DSRB: 2013/00457
• Study Type: interventional
• Target: 144
• Locations: 3 countries
• Sites: 7

Brief 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

Conditions

Heart Failure

Keywords

Heart Failure; Heart Failure with Preserved Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Compare the changes in left atrial volume index (LAVi) and/or left ventricular mass index (LVMi) on cardiac magnetic resonance imaging (cMRI) between baseline and 6 months

  baseline, 6 months

Secondary Outcomes (6)

• Compare the changes in exercise capacity and functional status as assessed by maximal oxygen consumption (VO2max) on cardiopulmonary exercise testing and by 6-minute walk test between baseline and 6 months

  baseline, 6 months

• Compare the changes in chocardiographic grade of diastolic dysfunction as assessed by Tissue Doppler E/e', (a non-invasive estimate of left atrial filling pressure).

  baseline, 6 months

• Compare the changes in biomarkers of cardiac load and interstitial fibrosis as assessed by plasma assays of relevant biomarkers

  baseline, 6 months

• Compare the changes in ventricular-vascular function as evaluated by echocardiographic measures of arterial elastance, Left Ventricular (LV) end-systolic elastance, LV filling pressure, and LV diastolic stiffness between baseline and 6 months

  baseline, 6 months

• Compare the changes of Quality of life as assessed by the Minnesota Living with Heart Failure between baseline and 6 months.

  baseline, 6 months

Study Arms (2)

Renal Denervation and standard medical management

EXPERIMENTAL

Renal Denervation (RDN) is a simple catheter procedure removing excess nerve signals to and from the kidneys. The renal denervation system consists of a small steerable treatment catheter and an automatically-controlled treatment delivery generator. A guiding catheter is inserted through a tiny incision in the groin into the femoral artery to direct the treatment catheter to the renal arteries. The treatment catheter delivers high -frequency radio waves, called radiofrequency wavees, to 4-6 locations within each of the two renal arteries. the energy delivered is about 8 watts and aims to disrupt the nerves and lower blood pressure over a period of months. The procedure takes 40-60 minutes.

Device: Renal Denervation

Contorl and Standard Medical Management

NO INTERVENTION

Continued medical management will comprise management of all cardiovascular risk factors (hypertension, diabetes, dyslipidaemia) in accord with international guidelines. Lifestyle and dietary counselling will also be part of the patient management. As there is no established evidence-based pharmacotherapy for HFPEF per se, therapy aimed at HF specifically will adopt treatments recommended for HFREF with prescription of diuretic, ACE inhibitor/ARB, beta blocker and mineralocorticoid antagonist accordingly.

Interventions

Renal Denervation DEVICE

Also known as: Symplicity Catheter System, renal sympathetic denervation, renal ablation

Renal Denervation and standard medical management

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with HFPEF (based upon ESC diagnostic criteria9)
• Symptoms and signs of heart failure; NYHA Class II or higher
• Left ventricular ejection fraction 50% or greater on echocardiography
• Echocardiographic evidence of left ventricular diastolic dysfunction (echo-Doppler E/e' \> 15 )AND/OR plasma NTproBNP \> 220pg/ml.
• Episode of acute decompensation (ADHF)
• Patients with and without background hypertension may be recruited. In the case of patients with background hypertension (ie history of fulfilling the diagnostic WHO criteria for hypertension: SBP \> 140 mmHg and/or DBP \> 90 mmHg) those with both controlled (\<140/90mmHg by 24 hour ambulatory BP) and inadequately controlled BP (on 3 anti-hypertensive drugs including a diuretic) can be recruited.

You may not qualify if:

• Known secondary cause of hypertension
• Renal artery stenosis \>30% or anatomy otherwise unsuitable for RDN.
• Heart failure with reduced LV ejection fraction (LVEF \< 50%).
• Estimated glomerular filtration rate (eGFR) of \< 30mL/min/1.73m2 (MDRD calculation).
• Systolic blood pressure \< 105mmHg.
• Implanted pacemaker, prosthetic heart valve or other precluding cMR scanning.
• Medical condition adversely affecting safety and/or effectiveness of the participant (including peripheral vascular disease, abdominal aortic aneurysm, thrombocytopenia or atrial fibrillation).
• Pregnant, nursing or planning to be pregnant.
• Uncontrolled atrial fibrillation, ie with heart rate over 120 bpm

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• University of Otago: collaborator
• Wellington Hospital: collaborator
• University of Auckland, New Zealand: collaborator
• Monash University: collaborator
• Tan Tock Seng Hospital: collaborator
• Changi General Hospital: collaborator
• Singapore Clinical Research Institute: collaborator

Study Sites (7)

Monash University

Melbourne, Australia

NOT YET RECRUITING

The University of Auckland

Auckland, New Zealand

RECRUITING

University of Otago

Christchurch, New Zealand

RECRUITING

Wellington Hospital

Wellington, New Zealand

RECRUITING

Changi General Hospital

Singapore, Singapore

RECRUITING

National University Heart Centre

Singapore, Singapore

RECRUITING

Tan Tock Seng Hospital

Singapore, Singapore

RECRUITING

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Arthur Mark Richards, MBChB, MD (Distinction), PhD

  University of Otago, Christchurch

  STUDY CHAIR

• Henry Krum, MBBS, PhD, FRACP, FCSANZ

  Monash University

  PRINCIPAL INVESTIGATOR

• Carolyn Lam Su Ping, MBBS, MRCP, MS

  National University Heart Centre, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark Richards Arthur, MBChB, MD (Distinction), PhD

CONTACT

mdcarthu@nus.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2013
• First Posted: January 20, 2014
• Study Start: October 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2016
• Last Updated: January 16, 2015

Record last verified: 2015-01

Locations

NZ (3); SG (3); AU (1)