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Trial registered on ANZCTR


Registration number
ACTRN12613000360718
Ethics application status
Approved
Date submitted
31/03/2013
Date registered
5/04/2013
Date last updated
4/04/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Neuromodulation for Uncontrolled Hypertension
Scientific title
For Adults with Uncontrolled Hypertension, is Neuromodulation an Effective Adjunct to Pharmaceutical Intervention for Reduction in Systolic Blood Pressure.
Secondary ID [1] 282219 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Uncontrolled hypertension 288736 0
Condition category
Condition code
Cardiovascular 289093 289093 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1 (Treatment Arm): Implanted with Subcutaneous Neuromodulation System (SNS) and fitted within 2 weeks of implantation. The bilateral implantation procedure is done under local anesthesia in an outpatient setting. Each device takes approximately 10 to 15 minutes per arm.
SNS therapy for hypertension provides electrical stimulation to the median nerve from a small self-contained implant placed in the subcutaneous space over the median nerve in the forearm. Subjects receive bilateral implants in a simple procedure under local anesthetic. The implant is programmed in manufacturing to provide once weekly 30 minute stimulation sessions. In between sessions, the implant is dormant. The implant is set in manufacturing to provide low rate stimulation. Amplitude is settable with a programming controller, and is ramped up to the highest comfortable level for the subject during a fitting session that lasts approximately 45 minutes which includes the initial 30 minute therapy session. The device contains a battery that will operate for approximately2-3 years, before the device requires replacement. Next generation systems are expected to last 5 years.
Intervention code [1] 286832 0
Treatment: Devices
Comparator / control treatment
Arm 2(Control Arm): Implanted with Subcutaneous Neuromodulation System and fitted after 6 months of data collection when only treated with drug regimen. The control arm will have the SNS in place but the stimulation will not be activated. Note that they will have a "sham fitting" by the sponsor technician that will allow the subjects and physicians to be blinded.
Control group
Active

Outcomes
Primary outcome [1] 289202 0
The primary endpoint is change in Office Systolic Blood Pressure (SBP) using an automatic sphygmomanometer and following the American Heart Association guidelines.
Timepoint [1] 289202 0
From baseline to six months post implant and activation in total patient cohort.
Secondary outcome [1] 302025 0
Difference in office systolic blood pressure in those in whom the SNS is implanted and activated compared with those in whom it is implanted and not activated using an automatic sphygmomanometer and following the American Heart Association Guidelines.
Timepoint [1] 302025 0
Difference in office systolic blood pressure at 6 months in those in whom the SNS is implanted and activated compared with those in whom it is implanted and not activated

Eligibility
Key inclusion criteria
1. Individual has a systolic blood pressure measured at greater than or equal to 140mmHg in the most recent medical history and which is confirmed with in-office blood pressure measured at both an initial screening and baseline screening visit and also with a 24 hour Ambulatory blood pressure, despite adhering to a stable anti-hypertensive drug regimen for a minimum of two weeks prior to enrollment of three or more anti- hypertensive medications including a diuretic

OR

2. Individual has a systolic blood pressure measured at greater than or equal to 160mmHg in the most recent medical history and which is confirmed with in-office blood pressure measured at both an initial screening and baseline screening visit and also with a 24 hour Ambulatory blood pressure, despite adhering to a stable anti-hypertensive drug regimen for a minimum of two weeks prior to enrollment of two or more anti- hypertensive medications and has documented allergy to or intolerance of additional antihypertensive medications.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Individual in whom medications are expected to change during the next 12 months
2. Individual does not agree to have all study procedures performed, and is not competent and willing to provide written, informed consent to participate in this clinical study.
3. Individual has type 1 diabetes mellitus.
4. Individual has experienced a myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within six months of the screening visit.
5. Individual has a scheduled or planned surgery, cardiovascular intervention, or dialysis in the next six months.
6. Individual has hemodynamically significant valvular heart disease for which reduction of blood pressure would be considered hazardous.
7. Individual has any serious medical condition with a prognosis of <2 years.
8. Individual has significant anemia (hemoglobin <100g/L), thrombocytopenia (platelets <100x109/L) or a severe bleeding disorder eg. hemophilia.
9. Individual has secondary hypertension (other than associated with obstructive sleep apnea)
10. Individual is pregnant, nursing or planning to be pregnant.
11. Individual has known or suspected history of medication non-compliance
12. Individual has known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or would be unlikely or unable to comply with study follow-up requirements.
13. Patient has undergone renal denervation.
14. Individual has severe renal dysfunction (CKD V, eGFR <15)
15. Individual has another implantable stimulation device including a cardiac pacemaker, ICD, spinal cord stimulator, brain stimulator, vagus nerve stimulator, peripheral nerve stimulator, or cochlear implant.
16. Patient is scheduled to have an MRI.
17. Individual is currently enrolled in another investigational drug or device trial that has not reached its primary endpoint.

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)
Interested adults who are known or present at the research site with uncontrolled hypertension may be initially screened for inclusion in the study. Patients’ medical records will be reviewed for inclusion/exclusion criteria. The patient’s medication regimen will also be reviewed.

Patients who initially qualify will be scheduled for a screening visit to assess general health and hypertension. An in-office blood pressure measured at the screening visit should be taken according to American Heart Association guidelines confirming systolic hypertension of greater than or equal to 140 mmHg. Patients will also be questioned for inclusion/exclusion criteria in addition to medical record review. General health to participate in the study we be further evaluated by the investigator at the screening visit.
The informed consent will be presented to the individual for consideration at the screening visit. The individual will be given adequate time to have all questions answered and to carefully consider participation. If, after understanding the purpose, potential risk, potential benefits, and requirements of the study, as well as his or her rights as a research participant, the individual agrees to participate as evidenced by providing written informed consent, the subject will be enrolled to enter the baseline period. The subject should be allowed to take informed consent documents home for further consideration, if needed, and scheduled with an additional visit to complete the screening visit. Informed Consent shall be included in the patient’s medical record file and noted in the screening CRF. At this time, the subject will be provided and trained to use a 24 hour ambulatory blood pressure monitor (ABPM) and provided a medication log to keep for 2 weeks. Subjects who continue to be eligible after completing baseline will be scheduled for implantation. Two weeks after implantation, subjects will return for fitting and be randomized into control or treatment groups. Randomization will be stratified by study center and will be at a 1:1 ratio to treatment or control. Investigators, medical staff and subjects will not be informed of subjects’ randomization, and thus are blinded. Randomization will be provided to the programming technician, and marked on the fitting CRF. This will be placed into a closed envelope for inclusion in the study file, and can be viewed by the study coordinator, programming technician, and study monitors until completion of the subject’s completion of the 3 month follow up (control period).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomization will be used to ensure balance in numbers during the trial. Patients will be divided into blocks per randomization region. The block sizes and sequences are not delineated in the protocol in order to ensure that there is no selection bias and the blind is maintained.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Efficacy (BP) analyses will be generated for the ITT, PP, Treated and Responder analysis sets, with the analysis on the ITT set being the primary analysis. Safety analysis will be performed on the safety analysis set:

a) Intent-to-Treat (ITT): All randomized patients meeting the inclusion criteria of the study who are not ineligible because of exclusion criteria; this is the primary analysis population for the efficacy analysis on blood pressures. Subjects are analyzed according to the treatment to which they were randomized.

b) Per-Protocol (PP): The subset of ITT subjects who complete the three months of follow-up and who received the treatment to which they were randomized. Subjects meeting these criteria will be part of the PP population regardless of whether or not they have had medication changes for low BP or high BP.

c) Safety (through three months post-randomization): All subjects randomized to Control and all subjects randomized to Treatment who received electrical stimulation through implantation of the SNS.

d) Treated: All subjects who received 3 months of electrical stimulation through implantation of the SNS.

e) Responder Subsets: Subjects who received electrical stimulation through implantation of the SNS and who achieve at least a 10mmHg reduction in office systolic BP from baseline to three or six months post treatment within a treated set.

An apriori analysis of treatment cohort compared with the control as well as the whole subject population assuming an approximate mean differential of 20 mm HG and a standard deviation of 25 yielded a study sample size of approximately 102 to achieve a minimum of 80% power.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/07/2013
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
102
Accrual to date
Final
Recruitment outside Australia
Country [1] 4962 0
New Zealand
State/province [1] 4962 0
Country [2] 5963 0
Canada
State/province [2] 5963 0
Country [3] 5964 0
Taiwan, Province Of China
State/province [3] 5964 0

Funding & Sponsors
Funding source category [1] 286979 0
Commercial sector/Industry
Name [1] 286979 0
Valencia Technologies, Corp.
Country [1] 286979 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Valencia Technologies, Corp.
Address
28464 Westinghouse
Valencia, CA 91355
Country
United States of America
Secondary sponsor category [1] 285768 0
None
Name [1] 285768 0
Address [1] 285768 0
Country [1] 285768 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289029 0
Health and Disability Ethics Committee
Ethics committee address [1] 289029 0
Ethics committee country [1] 289029 0
New Zealand
Date submitted for ethics approval [1] 289029 0
26/04/2013
Approval date [1] 289029 0
29/07/2013
Ethics approval number [1] 289029 0
HDECS 13/STH/60

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 38870 0
Dr Mark Webster
Address 38870 0
Consultant Cardiologist
Director, Cardiac Catheterisation Laboratories
Auckland City Hospital
Private Bag 92-024
Auckland 1023

Country 38870 0
New Zealand
Phone 38870 0
+6493074949
Fax 38870 0
Email 38870 0
MWebster@adhb.govt.nz
Contact person for public queries
Name 38871 0
Karen Jaffe
Address 38871 0
Manager, Clinical Research and Regulatory Affairs
28464 Westinghouse
Valencia, CA 91355
Country 38871 0
United States of America
Phone 38871 0
+19492327045
Fax 38871 0
Email 38871 0
kjaffe@valenciatechnologies.com
Contact person for scientific queries
Name 38872 0
Jeff Greiner
Address 38872 0
Manager, Clinical Research and Regulatory Affairs
28464 Westinghouse
Valencia, CA 91355
Country 38872 0
United States of America
Phone 38872 0
+16617751414
Fax 38872 0
Email 38872 0
jgreiner@valenciatechnologies.com

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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseFeasibility of a Fully Implanted, Nickel Sized and Shaped Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome with Urgency Urinary Incontinence.2019https://dx.doi.org/10.1016/j.juro.2018.10.017
EmbaseTwelve-month Durability of a Fully-implanted, Nickel-sized and Shaped Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome with Urgency Urinary Incontinence: A Single-Arm, Prospective Study.2021https://dx.doi.org/10.1016/j.urology.2021.04.039
N.B. These documents automatically identified may not have been verified by the study sponsor.