Heart FailurePhase 2RESPECT-HFNCT02041130
Renal Denervation in Heart Failure Patients With Preserved Ejection Fraction (RESPECT-HF)
A Phase 2 study testing Renal Denervation in people with Heart Failure, run by National University Hospital, Singapore at 7 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Renal Denervation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 144 participants
- Where
- 7 sitesin 3 countries
- Study dates
- Oct 2013to Dec 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
7 sites in 3 countries.
Mark Richards Arthur, MBChB, MD (Distinction), PhD contact
7 sites in 3 countries
New Zealand3 sites, 3 recruiting
- Recruiting
The University of Auckland
Auckland
- Recruiting
University of Otago
Christchurch
- Recruiting
Wellington Hospital
Wellington
Singapore3 sites, 3 recruiting
- Recruiting
Changi General Hospital
Singapore
- Recruiting
National University Heart Centre
Singapore
- Recruiting
Tan Tock Seng Hospital
Singapore
About this study
Official title: Renal Sympathectomy in Heart Failure (the RESPECT-HF Study) - a Study of Renal Denervation for Heart Failure With Preserved Ejection Fraction
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
Read the 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:
- improve exercise capacity and functional status.
- reduce E/e' and echocardiographic grade of diastolic dysfunction.
- reduce circulating biomarkers of cardiac load, interstitial fibrosis and inflammation.
- improve ventricular-vascular function.
- improve Minnesota Living with Heart Failure (MLWHF) scores.
- 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
- Being tested
- Renal Denervation
- Keywords
- Heart Failure, Heart Failure with Preserved Ejection Fraction
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Renal DenervationDevice
Also called Symplicity Catheter System, renal sympathetic denervation, renal ablation
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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).
Measured: baseline, 6 months
Compare the changes in biomarkers of cardiac load and interstitial fibrosis as assessed by plasma assays of relevant biomarkers
The biomarkers of cardiac load and interstitial fibrosis as assessed by plasma assays of markers of ventricular and atrial haemodynamic load, other neurohormones contributing to HF pathophysiology, cytokine markers of inflammation and remodelling, markers of cardiac fibrosis, a marker of cardiomyocyte loss.
Measured: 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
Measured: baseline, 6 months
Compare the changes of Quality of life as assessed by the Minnesota Living with Heart Failure between baseline and 6 months.
Measured: baseline, 6 months
Compare the difference in composite end-point of death or hospitalization with Heart Failure between control arm and treatment arm
Measured: baseline, 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2014 (estimated)
- Study startOct 2013
- Primary completionDec 2015 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 144 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- University of Otago, Wellington Hospital, University of Auckland, New Zealand, Monash University, Tan Tock Seng Hospital, Changi General Hospital, Singapore Clinical Research Institute
- Responsible party
- Sponsor
- Investigators
- Arthur Mark Richards, MBChB, MD (Distinction), PhD, Study chair, University of Otago, ChristchurchHenry Krum, MBBS, PhD, FRACP, FCSANZ, Principal investigator, Monash UniversityCarolyn Lam Su Ping, MBBS, MRCP, MS, Principal investigator, National University Heart Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02041130
- Sponsor's protocol ID
- DSRB: 2013/00457
- Acronym
- RESPECT-HF
- Status last verified
- Jan 2015
- First submitted
- 28 Oct 2013
- Last updated
- 16 Jan 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Renal Sympathectomy in Heart Failure (the RESPECT-HF Study) - a Study of Renal Denervation for Heart Failure With Preserved Ejection Fraction
- ClinicalTrials.gov ID
- NCT02041130
- Acronym / sponsor ID
- RESPECT-HF / DSRB: 2013/00457
- Conditions
- Heart Failure
- Keywords
- Heart Failure, Heart Failure with Preserved Ejection Fraction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 144 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Collaborators
- University of Otago, Wellington Hospital, University of Auckland, New Zealand, Monash University, Tan Tock Seng Hospital, Changi General Hospital, Singapore Clinical Research Institute
- Study start
- Oct 2013
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 20 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- improve exercise capacity and functional status.
- reduce E/e' and echocardiographic grade of diastolic dysfunction.
- reduce circulating biomarkers of cardiac load, interstitial fibrosis and inflammation.
- improve ventricular-vascular function.
- improve Minnesota Living with Heart Failure (MLWHF) scores.
- 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%.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Renal Denervation and standard medical management | Experimental | Device: Renal DenervationRenal 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. |
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with HFPEF (based upon ESC diagnostic criteria9)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Renal DenervationAlso: Symplicity Catheter System, renal sympathetic denervation, renal ablation | Device | Renal Denervation and standard medical management |
Primary outcome
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
Time frame: baseline, 6 months
6 secondary outcomes
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
Time frame: 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).
Time frame: baseline, 6 months
Compare the changes in biomarkers of cardiac load and interstitial fibrosis as assessed by plasma assays of relevant biomarkers
Time frame: 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
Time frame: baseline, 6 months
Compare the changes of Quality of life as assessed by the Minnesota Living with Heart Failure between baseline and 6 months.
Time frame: baseline, 6 months
Compare the difference in composite end-point of death or hospitalization with Heart Failure between control arm and treatment arm
Time frame: baseline, 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Richards Arthur, MBChB, MD (Distinction), PhD contact
Arthur Mark Richards, MBChB, MD (Distinction), PhD study chair
University of Otago, Christchurch
Henry Krum, MBBS, PhD, FRACP, FCSANZ principal investigator
Monash University
Carolyn Lam Su Ping, MBBS, MRCP, MS principal investigator
National University Heart Centre, Singapore
7 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Renal Denervation in people with Heart Failure, run by National University Hospital, Singapore at 7 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in New Zealand, Singapore, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mark Richards Arthur, MBChB, MD (Distinction), PhD (mdcarthu@nus.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: baseline, 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2015.