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Trial registered on ANZCTR


Registration number
ACTRN12615000203550
Ethics application status
Approved
Date submitted
7/11/2013
Date registered
3/03/2015
Date last updated
12/01/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Renal Denervation in Heart Failure
Scientific title
A phase II randomised, controlled pilot study to evaluate the safety and feasibility of renal denervation in heart failure patients on maximal medical treatment
Secondary ID [1] 283344 0
Nil
Universal Trial Number (UTN)
Trial acronym
Renal Denervation in Heart Failure (RDN HF)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Failure 290237 0
Condition category
Condition code
Cardiovascular 290628 290628 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Catheter-based renal denervation which is a medical procedure using a device. In this study, a multi-electrode catheter-based renal denervation system known as the EnligHTN System, is used. The renal denervation catheter delivers radiofrequency (RF) energy through the wall of the blood vessels supplying the kidneys (renal arteries) in order to disrupt the sympathetic nerves that lead to the kidneys. Each electrode on the catheter may independently administer 8 W of power over 60 seconds per ablation set. The number of ablation sets is determined by the number and area of vessels to be treated. The average duration of the overall procedure is 1 to 2 hours.
Intervention code [1] 288065 0
Treatment: Devices
Intervention code [2] 291268 0
Treatment: Surgery
Comparator / control treatment
Standard Treatment. The standard treatment employed in this study for people experiencing heart failure will be in accordance with the 2013 ACCF/AHA Heart Failure Guidelines. All participants will continue to receive optimal medical therapy for heart failure including anti-congestive heart failure (CHF) medications and lifestyle counselling.

Control group participants will be maintained on medical therapy for 6 months. Once 6 month follow-up is complete, participants will have the option to undergo treatment with catheter-based renal denervation.
Control group
Active

Outcomes
Primary outcome [1] 290641 0
Safety of renal denervation in heart failure patients using a multi-electrode catheter-based renal denervation system.

The primary safety endpoint is the occurrence of any serious adverse events (SAEs) attributed to the renal denervation procedure. Such SAEs will include: renal artery dissection or perforation; serious groin site complication; reduced renal function or new renal artery stenosis.
Timepoint [1] 290641 0
The primary safety analysis will be performed on acute procedural Safety (incidence of renal artery dissection or perforation requiring intervention and incidence of serious groin complications); incidence of “new” renal artery stenosis at 6 months post procedure and reduction in renal function (defined as eGFR drop of >25% in comparison to baseline) at 6 months post procedure.
Primary outcome [2] 294391 0
Feasibility of renal denervation in heart failure patients using a multi-electrode catheter-based renal denervation system.

The feasibility of performing renal denervation in heart failure patients will be determined by analysis of any overall health benefit/s (improvements in any secondary outcomes)as opposed to the emergence of any health risk/s, as determined by the occurence of adverse procedural and/or safety events.
Timepoint [2] 294391 0
12 months
Secondary outcome [1] 304965 0
Change in functional status.




Timepoint [1] 304965 0
Changes in functional status will be measured using the NYHA Classification and 6-Minute Hall Walk test. Comparison between the groups will occur at baseline, 6 months post-randomisation (Control only) and 6 months post RDN (Treatment and Control).
Secondary outcome [2] 304966 0
Change in left ventricular function.

Timepoint [2] 304966 0
This will be assessed using trans-thoracic echocardiography measurements such as: LVEF, LVESV and diastolic function.
Comparison between the groups will occur at baseline, 6 months post-randomisation (Control only) and 6 months post RDN (Treatment and Control).
Secondary outcome [3] 304967 0
Change in renal function.
Timepoint [3] 304967 0
Comparison between groups at 6 months post-randomisation (Control only) and 6 months post RDN (Treatment and Control) for reduction in renal function (defined as eGFR drop of >25% in comparison to baseline).
Secondary outcome [4] 313184 0
Change in blood pressure.
Timepoint [4] 313184 0
Comparison between groups at 6 months post-randomisation (Control only) and 6 months post RDN (Treatment and Control) for changes in blood pressure.
Secondary outcome [5] 313187 0
Change in Quality of Life questionnaire responses.
Timepoint [5] 313187 0
Comparison between groups at 6 months post-randomisation (Control only) and 6 months post RDN (Treatment and Control) for changes in Kansas City Cardiomyopathy Questionnaire responses.
Secondary outcome [6] 313188 0
Change in biomarker Pro-BNP.
Timepoint [6] 313188 0
Comparison between groups at 6 months post-randomisation (Control only) and 6 months post RDN (Treatment and Control) for change in bio-marker Pro-BNP which is measured by serum assay.
Secondary outcome [7] 313191 0
Change in metabolic function.
Timepoint [7] 313191 0
Change in metabolic function will be measured by biochemistry (UEC, glucose, HbA1c) with comparison between groups at 6 months post-randomisation (Control only) and 6 months post RDN (Treatment and Control).

Eligibility
Key inclusion criteria
1. Able to comprehend requirements and provide consent.
2. Males or females greater than or equal to 18years.
3. Established congestive heart failure with NYHA Class II-III
4. Left Ventricular Ejection Fraction (LVEF) less than or equal to 35% on echocardiography.
5. Adequate renal function with estimated GFR greater than or equal to 30 mL/min.
6. Optimal stable medical therapy for heart failure for at
least 3 months prior to study entry as per ACCF/AHA
guidelines.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Renal artery abnormalities (i.e. too small, presence of significant stenosis, prior angioplasty procedure, multiple main renal arteries).
2. Single functioning kidney.
3. End Stage Renal Disease requiring haemo-dialysis or
renal transplant.
4. Unstable vascular syndromes, such as myocardial
infarction, unstable angina pectoris or cerebro-vascular
accident, within 3 months.
5. Systolic blood pressure less than 100mmHg.
6. Haemodynamically significant valvular heart disease.
7. Pregnant, nursing or planning on becoming pregnant
during the course of the study.
8. Enrolled in, or intend to participate in, another
investigational drug or device trial.
9. Any concurrent disease or condition that, in the opinion
of the investigator, would make the subject unsuitable
for participation in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Approximately 20 participants, with symptomatic congestive heart failure despite maximal medical treatment, will be enrolled in the study. Eligible participants will undergo screening procedures to determine individual suitability to undergo renal denervation. Those who meet all selection criteria following screening will proceed to randomisation.

Assignment to the study group (treatment or control) will be 1:1 with concealed allocation using numbered sealed opaque envelopes. The envelopes will be prepared and allocated in sequence by staff who are independent of the research team.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation sequence will be according to a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Approximately 50% of the participants will be randomised to receive up-front treatment whilst the remaining 50% of participants act as the control group. After 6 months, the control group participants may cross-over to receive renal denervation treatment.
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
As a pilot study, the sample size is limited to 20 patients. The study is designed to provide initial evidence of safety and demonstration of physiologic response. The data from this 20 patient study may be used to provide information to design and conduct a larger multi-center, controlled clinical trial, which will be performed to provide valid scientific and clinical evidence and reasonable assurance that the device is safe and effective.

All clinical test results will be listed and summarized by treatment and time with appropriate descriptive statistics (number of observations, mean and standard deviation (SD) or median with minimum and maximum) for continuous measures. Nominal and ordinal scale measures will be summarized with frequency tables, and percentages, as appropriate.

Demographic data, medical history, concomitant disease and concomitant medication will be summarized by means of descriptive statistics (number, mean, SD, median, minimum and maximum) or frequency tables, stratified by treatment.

Review of safety tables, listings and figures will be performed by a designated medical monitor. The safety tables will allow a view of changes from baseline in findings from 12-lead ECGs, vital signs, clinical laboratory values, and adverse events. No statistical testing will be executed for safety measures.

The efficacy endpoints of TTE parameters, time to MACCE, 6-Minute Hall Walk, NYHA class, metabolic and renal function, Pro BNP, blood pressure and quality of life survey scores will be compared at baseline and at 6 months using a paired t-test.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
19/01/2016
Actual
Date of last participant enrolment
Anticipated
19/01/2017
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 3467 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment postcode(s) [1] 9243 0
2305 - New Lambton Heights

Funding & Sponsors
Funding source category [1] 288075 0
Charities/Societies/Foundations
Name [1] 288075 0
JHH Charitable Trust Fund
Country [1] 288075 0
Australia
Funding source category [2] 290765 0
Commercial sector/Industry
Name [2] 290765 0
St Jude Medical
Country [2] 290765 0
Australia
Primary sponsor type
Individual
Name
Dr Suku Thambar
Address
Cardiology Department
John Hunter Hospital
Lookout Road
New Lambton Heights
NSW 2305
Country
Australia
Secondary sponsor category [1] 286799 0
None
Name [1] 286799 0
Address [1] 286799 0
Country [1] 286799 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290002 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 290002 0
Locked Bag 1
New Lambton
NSW 2305
Ethics committee country [1] 290002 0
Australia
Date submitted for ethics approval [1] 290002 0
25/09/2013
Approval date [1] 290002 0
04/12/2013
Ethics approval number [1] 290002 0
13/10/16/3.02

Summary
Brief summary
Renal Denervation in Heart Failure (RDN HF) is a physician-initiated pilot study involving staff of the Cardiology, Radiology and Nephrology Departments of the John Hunter Hospital, Newcastle, NSW.

RDN HF is a first-in-human clinical trial of catheter-based renal denervation in heart failure patients. It uses a TGA approved device called the EnligHTN System, manufactiured by St Jude Medical.

The study aims to evaluate the safety of renal denervation using the device and the effectiveness of the technique in improving the symptoms of heart failure.

This is a prospective, randomised, controlled single centre study that will enrol approximately 20 participants with symptomatic congestive heart failure despite maximal medical treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 43418 0
Dr Suku Thambar
Address 43418 0
Cardiology Department
John Hunter Hospital
Lookout Road
New Lambton Heights
NSW 2305
Country 43418 0
Australia
Phone 43418 0
+61-2-4921 4204
Fax 43418 0
+61-2-4921 4210
Email 43418 0
[email protected]
Contact person for public queries
Name 43419 0
Ms Melissa Chaplin
Address 43419 0
Clinical Trials Coordinator
Cardiology Department
John Hunter Hospital
Lookout Road
New Lambton Heights NSW 2305
Country 43419 0
Australia
Phone 43419 0
+61-2-4921 4216
Fax 43419 0
+61-2-4921 4210
Email 43419 0
[email protected]
Contact person for scientific queries
Name 43420 0
Dr Suku Thambar
Address 43420 0
Cardiology Department
John Hunter Hospital
Lookout Road
New Lambton Heights
NSW 2305
Country 43420 0
Australia
Phone 43420 0
+61-2-4921 4204
Fax 43420 0
+61-2-4921 4210
Email 43420 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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