Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000562774
Ethics application status
Approved
Date submitted
8/05/2013
Date registered
17/05/2013
Date last updated
23/07/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Renal Sympathectomy in dialysis-dependent patients to reduce cardiovascular risk. A pilot study
Scientific title
Renal endoluminal denervation to reduce sympathetic overdrive in dialysis-dependent patients.
Secondary ID [1] 282467 0
Nil
Universal Trial Number (UTN)
U1111-1142-8219
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
End Stage Kidney Disease 289086 0
Condition category
Condition code
Renal and Urogenital 289426 289426 0 0
Kidney disease
Cardiovascular 289427 289427 0 0
Other cardiovascular diseases
Cardiovascular 289428 289428 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The denervation procedure itself involves an endovascular catheter-based approach to disrupt renal sympathetic nerves using radiofrequency (RF) ablation. This is a single intervention, which takes approximately 40 minutes for the proceedure in the cardiology angiography suite. This procedure will by performed by Assoc Prof G Wilkins. Data will be collected at baseline (over a week prior to the procedure) and following renal denervation at 1, 3, and 12 months. The impact of renal denervation will be measured by changes in blood pressure; cardiac function by way of holter monitoring and echocardiographic measurement of left ventricular function; multiunit postganglionic sympathetic nerve activity (MSNA) will be recorded through the use of microneurography in the peroneal nerve; circulating plasma catecholamines as an indirect marker of sympathetic activity
Intervention code [1] 287113 0
Treatment: Devices
Comparator / control treatment
An open interventional study with each participant acting as their own control. Each individual will have baseline studies of blood pressure, cardiac function (holter monitoring for 48 hours to assess beat to beat variability and echocardiographic measurements of left ventricular function), MSNA studies, blood samples taken to measure circulating plasma catecholamines. Following the baseline measurements, the individual will undergo the endoluminal ablation of their renal sympathetic nerves by radiofrequency ablation. They will then be followed closely for the next 12 months, with repeat measurements of the above parameters at 1 month, 3 months and 12 months.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289529 0
Changes in renal sympathetic nerve activity as measured by multiunit sympathetic nerve activity
Timepoint [1] 289529 0
Baseline prior to the procedure, then at 1month, 3 months and 12 months after the procedure
Secondary outcome [1] 302688 0
Changes in cardiac function as assessed by beat to beat variability on holter monitoring, echocardiographic changes in left ventricular function and volume, and changes in blood pressure.
Timepoint [1] 302688 0
Baseline prior to the procedure and then at 1 month, 3 months, 12 months after the procedure
Secondary outcome [2] 302689 0
Changes in circulating plasma catecholamines and beat to beat variability in heart rate as markers of systemic sympathetic activity after the intervention compared to baseline values.
Timepoint [2] 302689 0
Baseline prior to the procedure and at 1 month. 3 months, 12 months after the procedure.

Eligibility
Key inclusion criteria
Age > 18 and able to give consent.
On dialysis for at least 3 months.
Clinically stable with no evidence of fluid overload, recent myocardial ischaemia or heart attack.
Blood pressure > 130/90 despite medications.
They must have intact native renal kidneys
Minimum age
8 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with significant renovascular abnormalities will not permitted to undergo the intervention. Anatomic abnormalities including multiple main renal arteries, short length main renal arteries, failed renal transplant, are exclusion criteria.
Inability to give consent.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
A pilot feasibility study using the individual as their own control. Participants will be enrolled from the dialysis unit and out patient clinics.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
An open pilot study.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Statistical Assessment: MSNA levels from baseline to the above time points (1,3, 12 months) will be evaluated to calculate mean change, as well as 95% CIs. This change will be assessed by repeated-measures ANOVA with pairwise comparison of significant values. A 2-tailed paired t test of P<0.05 to be regarded as statistically significant. Other measures such as 24 hour BP, holter monitoring, plasma catecholamines, LV Mass, etc will be compared in a similar manner.
This is a pilot study. There has been no such previous interventions in this group of patients. As such there is no data to inform a power calculation. This pilot study is to generate such data to inform a properly conducted randomised intervention trial in the future.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
28/02/2013
Actual
5/03/2013
Date of last participant enrolment
Anticipated
31/07/2013
Actual
23/07/2013
Date of last data collection
Anticipated
Actual
9/12/2014
Sample size
Target
15
Accrual to date
Final
9
Recruitment outside Australia
Country [1] 5069 0
New Zealand
State/province [1] 5069 0
Otago

Funding & Sponsors
Funding source category [1] 287247 0
Self funded/Unfunded
Name [1] 287247 0
Country [1] 287247 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
PO Box 56
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 285998 0
None
Name [1] 285998 0
Address [1] 285998 0
Country [1] 285998 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289226 0
Lower South Regional Ethics Committee
Ethics committee address [1] 289226 0
C/- Ministry of Health
PO Box 5013
Wellington 6145
Ethics committee country [1] 289226 0
New Zealand
Date submitted for ethics approval [1] 289226 0
Approval date [1] 289226 0
17/05/2012
Ethics approval number [1] 289226 0
LRS/12/05/012

Summary
Brief summary
Sudden cardiac death accounts for 26-45% of cardiovascular deaths in patients on dialysis. Sympathetic overactivity from the diseased kidneys is thought to contribute substantially to the high risk of cardiac events. The Australasian Kidney Trials Network (AKTN) have initiated a feasibility study of beta blocker therapy (BLOCADE) to test the tolerability of carvidolol in dialysis patients, with the view to a full study investigating sympathetic blockade on cardiac events in dialysis patients. Renal sympathetic denervation by radiofrequency ablation is a new novel alternative to medical therapy to reduce sympathetic overactivity. It would be logical to compare ß blocker therapy to renal denervation in dialysis patients in a head to head study. However, it is necessary to test the feasibility of renal denervation in this high risk group and to obtain appropriate data that would accurately inform end points and surrogate markers of the endpoints. The surrogate end points are changes in blood pressure, reduction in anti-hypertensive medications, changes in heart rate, changes in sympathetic nerve activity measured directly by microneurography and indirectly by changes in circulating neuro-hormones.
This application is for a feasibility study to inform scientific committee of the AKTN to allow a well designed intervention study to reduce sudden cardiac death in a very high risk population, that is patients on dialysis.
Trial website
Trial related presentations / publications
Endovascular renal denervation in end-stage kidney disease patients: Cardiovascular
protection – A proof-of-concept study
Neil A. Hoye, MBBS, Luke C. Wilson, PhD, Gerard T. Wilkins, MBChB, FRACP,
David L. Jardine, MBChB, FRACP, Tracey T. Putt, MBChB, MMed Sci, FRACP,
Ari Samaranayaka, PhD, John B.W. Schollum, MBChB, FRACP, Robert J. Walker,
MBChB, MD, FRACP
PII: S2468-0249(17)30111-0
DOI: 10.1016/j.ekir.2017.04.012
Reference: EKIR 154
To appear in: Kidney International Reports
Received Date: 5 February 2017
Revised Date: 17 April 2017
Accepted Date: 26 April 2017
Public notes

Contacts
Principal investigator
Name 39878 0
Prof Robert Walker
Address 39878 0
Department of Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country 39878 0
New Zealand
Phone 39878 0
+64274359552
Fax 39878 0
Email 39878 0
[email protected]
Contact person for public queries
Name 39879 0
Prof Robert Walker
Address 39879 0
Department of Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country 39879 0
New Zealand
Phone 39879 0
+64274359552
Fax 39879 0
Email 39879 0
[email protected]
Contact person for scientific queries
Name 39880 0
Prof Robert Walker
Address 39880 0
Department of Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country 39880 0
New Zealand
Phone 39880 0
+64274359552
Fax 39880 0
Email 39880 0
[email protected]

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