Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001524189
Ethics application status
Approved
Date submitted
13/09/2019
Date registered
5/11/2019
Date last updated
11/01/2023
Date data sharing statement initially provided
5/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The DeLIVER NZ Study will evaluate the safety of the Integrated Radio Frequency (iRF) Denervation System which is designed to improve blood pressure in patients with hypertnesion.
Scientific title
A Prospective, Single-Arm, Multi-Center Study of the Metavention Integrated Radio Frequency Denervation System to Improve Cardiometabolic Parameters in Hypertensive Subjects in New Zealand
Secondary ID [1] 299280 0
Nil known
Universal Trial Number (UTN)
Trial acronym
DELIVER NZ
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes Mellitus 314413 0
Hypertension 325161 0
Condition category
Condition code
Metabolic and Endocrine 312754 312754 0 0
Diabetes
Cardiovascular 322569 322569 0 0
Hypertension
Metabolic and Endocrine 322570 322570 0 0
Other metabolic disorders
Metabolic and Endocrine 322571 322571 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The iRF System is a percutaneous, catheter-based device which uses RF energy to circumferentially denervate the sympathetic nerves surrounding the common hepatic artery (CHA) and the renal arteries while minimizing injury to the arterial wall. The iRF System consists of the following components:
1. Single-use, monopolar, iRF Catheter that contains four (4) electrodes; provided sterile
2. Reusable, Radiofrequency Generator (RFG) with an Integrated Syringe Pump
3. Single-use, Generator Accessory Kit that contains a Syringe Cassette, two (2) tubing sets, and a waste collection bag, provided sterile
4. Single-use, Extension Cable, provided sterile

This procedure will be completed by an Interventional Cardiologist/Radiologist that has been trained on the device. It will occur in a catheterization laboratory or appropriate surgical setting. Up to 2 ablations will be administered during one procedure which will last no more than 2 hours.

Clinical observation and monitoring by the treating physician of the iRF system will be conducted throughout the procedure. The generator will also display system progress.
Each denervation cycle will provide 6 Watts of energy for 150 seconds to the common hepatic artery. Up to 2 cycles can be administered per procedure.
Intervention code [1] 315561 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 321381 0
The incidence rate of device related serious adverse device effects (SADEs) from time of Index Procedure through 90 days.
Some potential adverse events include but are not limited to: post operative pain, hematoma at the access site, tenderness and swelling at the catheter insertion site, allergic reaction to materials used, high or low blood pressure or damage to the liver. All events will be assessed using a variety of methods including: monitoring of vital signs, blood labs, glucose testing, imaging and self-reporting. Patients will be closely monitored by the study physician throughout study participation.
Timepoint [1] 321381 0
90 days post procedure
Secondary outcome [1] 374824 0
Glycemic control will be measured through blood labs of:
HbA1c
Timepoint [1] 374824 0
30, 90, 180 and 365 days post Index Procedure
Secondary outcome [2] 374825 0
Change in Office Blood Pressure assessed while in the physicians office using their standard method of assessing blood pressure with a sphygmomanometer.
Timepoint [2] 374825 0
30, 90, 180, and 365 days post Index Procedure
Secondary outcome [3] 374826 0
Change in ambulatory blood pressure monitoring (ABPM) measurements as measured by a 24 hour study.
Timepoint [3] 374826 0
30, 90, 180, and 365 days post Index Procedure
Secondary outcome [4] 374827 0
Clinical and laboratory assessment changes in:
Waist circumference measured through clinical examination (using standard of care items, such as a measuring tape).



Timepoint [4] 374827 0
30, 90, 180, and 365 days post Index Procedure
Secondary outcome [5] 374828 0
Adverse Event rate:
Summary of all reported adverse events during the study. At each follow-up visit, the investigator or designee will determine and report any adverse event occurrences using the Adverse Event Case Report From designed for this study. Adverse events can be reported at anytime throughout the study by the patient or study staff.
Timepoint [5] 374828 0
365 days post Index Procedure
Secondary outcome [6] 375641 0
Glycemic control will be measured through blood labs of:
Fasting Plasma Glucose
Timepoint [6] 375641 0
30, 90, 180, and 365 days post Index Procedure
Secondary outcome [7] 375642 0
Clinical and laboratory assessment changes in:
Alkaline phosphatase (ALP)
Timepoint [7] 375642 0
30, 90, 180, and 365 days post Index Procedure
Secondary outcome [8] 375643 0
Change in interstitial glucose measurements as obtained by continous glucose monitor (CGM) over a period of 5 days.
Timepoint [8] 375643 0
30, 90, 180, and 365 days post Index Procedure
Secondary outcome [9] 375644 0
Clinical and laboratory assessment changes in:
Blood levels of Triglycerides
Timepoint [9] 375644 0
30, 90, 180, and 365 days post Index Procedure
Secondary outcome [10] 376552 0
Changes in hepatic function by assessing blood levels of:
Alanine aminotransferase (ALT)
Timepoint [10] 376552 0
30, 90, 180, and 365 days post Index Procedure
Secondary outcome [11] 376553 0
Changes in hepatic functions by assessing blood levels of:
Aspartate aminotransferase (AST)
Timepoint [11] 376553 0
30, 90, 180, and 365 days post Index Procedure
Secondary outcome [12] 376554 0
Changes in hepatic function by assessing blood levels of:
Bilirubin (Total)
Timepoint [12] 376554 0
30, 90, 180, and 365 days post Index Procedure
Secondary outcome [13] 376555 0
Changes in hepatic functions by assessing blood levels of:
Albumin
Timepoint [13] 376555 0
30, 90, 180, and 365 days post Index Procedure
Secondary outcome [14] 376556 0
Changes in hepatic functions by assessing blood levels of:
Total protein (TP)
Timepoint [14] 376556 0
30, 90, 180, and 365 days post Index Procedure
Secondary outcome [15] 376557 0
Changes in hepatic functions by assessing blood levels of:
Globulin
Timepoint [15] 376557 0
30, 90, 180, and 365 days post Index Procedure

Eligibility
Key inclusion criteria
1) Age greater than or equal to 22 and less than or equal to 70 years old
2) Waist circumference greater than or equal to 102 cm (male) and greater than or equal to 88 cm (female)
3) Office systolic blood pressure (SBP) greater than or equal to 140 mmHg and less than 180 mmHg on a stable dose of antihypertensive medication(s) for at least 30 days
4) Documented daytime systolic ambulatory blood pressure (ABP) greater than or equal to 135 and less than 175 mmHg
5) Documented status of stable lifestyle modifications
6) Willing to comply with study requirements, including follow-up visits
7) Women of childbearing potential (WOCBP) must be using at least one acceptable method of contraception throughout the study
Minimum age
22 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
8) BMI of greater than 40 kg/m2
9) Type 1 diabetes mellitus or uncontrolled Type 2 diabetes (uncontrolled defined as HbA1c greater than 8.5 % / 69 mmol/mol)
10) One or more documented hyperglycemia episodes (requiring hospitalization) in the 90 days prior to Index Procedure
11) One or more severe hypoglycemic events (severe cognitive impairment requiring external assistance for recovery) in the 90 days prior to Index Procedure
12) One or more documented severe hypertensive crisis (persistent or elevated hypertension greater than 180 mmHg accompanied by clinical symptoms) in the 90 days prior to Index Procedure
13) A history of bariatric surgery, renal denervation, baroreflex activation therapy, or liver transplant, or these procedures are planned in the 365 days following Index Procedure
14) Any surgical procedure within 30 days prior to Index Procedure
15) History of or current symptomatic gallstones (e.g., cholecystitis, bile duct dilatation) without a cholecystectomy being performed(Note: subjects who have had a cholecystectomy are not excluded)
16) Previous hepatobiliary surgery/intervention that in the opinion of the investigator could preclude the ability to perform denervation of the common hepatic artery
17) Use of anticoagulation therapy which cannot be discontinued from 7 days before to 14 days after the Index Procedure
18) Any other condition(s) that would compromise the safety of the Subject or compromise study quality as judged by the Investigator
19) eGFR less than 45 mL/min/1.73 m2
20) History or diagnosis of proliferative retinopathy or advanced autonomic neuropathy (e.g., orthostatic hypotension attributable to autonomic neuropathy, a diagnosis of gastroparesis, or a clinical history strongly suggestive of delayed gastric emptying)
21) Myocardial infarction, unstable angina, stroke, or transient ischemic attack within the 180 days prior to Baseline, or has widespread atherosclerosis, with documented intravascular thrombosis or unstable plaques
22) Heart failure (New York Heart Association [NYHA] Class III-IV) at time of consent
23) Documented history of persistent or permanent atrial tachyarrhythmia
24) Chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnea
25) Night shift workers
26) Chronic regular use (e.g., daily use) of NSAIDs for 6 months or greater. Aspirin therapy is allowed.
27) Active implantable medical device (e.g., ICD or CRT-D, neuromodulator/spinal stimulator, baroreflex stimulator)
28) Known primary pulmonary HTN (greater 60 mmHg pulmonary artery or right ventricular systolic pressure)
29) Evidence of active infection within 7 days prior to Index Procedure
30) Documented history of chronic active inflammatory bowel disorders such as Crohn’s disease or ulcerative colitis
31) Individual has known pheochromocytoma, Cushing syndrome, primary hyperaldosteronism, coarctation of the aorta, untreated hyperthyroidism, untreated hypothyroidism, or primary hyperparathyroidism. (Note: Treated hyperthyroidism and treated hypothyroidism are permissible.)
32) Uncorrectable bleeding diathesis, platelet dysfunction, thrombocytopenia with platelet count <100,000/microliter, or documented coagulopathy
33) Any known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or for any reason in the opinion of the investigator, would be unlikely or unable to comply with study protocol requirements or whose participation may result in data analysis confounders
34) Significant weight loss within the last 6 months (e.g., greater than 10% total body weight loss)
35) Hepatic decompensation defined as the presence of any of the following:
a) Serum albumin less than 3.5 g/dL
b) International normalized ratio (INR) greater than 1.4 (unless due to therapeutic anticoagulants)
c) Total bilirubin greater than 2 mg/dL with the exception of Gilbert syndrome
d) History of esophageal varices, ascites, or hepatic encephalopathy
36) ALT or AST greater than 200 U/L
37) Diagnosis of liver cirrhosis
38) Chronic liver or biliary disease of the following etiology:
a) Evidence of Hepatitis B note: subjects who have recovered from a past Hepatitis B infection and demonstrated negative for Hepatitis B surface antigen are not excluded
b) History or evidence of Hepatitis C
c) History or evidence of current active autoimmune hepatitis
d) History or evidence of primary biliary cholangitis
e) History or evidence of primary sclerosing cholangitis
f) History or evidence of Wilson's disease
g) History or evidence of alpha-1-antitrypsin deficiency
h) History or evidence of hemochromatosis
i) History or evidence of drug-induced liver disease, as defined on the basis of typical exposure and history
j) Known bile duct obstruction
k) Suspected or proven liver cancer
39) History of acute or chronic pancreatitis
40) Subjects unable to undergo CT for any reason
41) Currently enrolled in any other investigational trial (participation in non-interventional registries is acceptable)
42) History of epilepsy
43) Iliac/femoral artery stenosis precluding insertion of the catheter
44) Human Immunodeficiency Virus (HIV)
45) Pregnant, nursing, or planning to become pregnant (documented negative pregnancy test result required documented within a maximum of 7 days before Index Procedure for all women of childbearing potential)
46) Limited life expectancy of less than 1 year at the discretion of the investigator

Anatomic Exclusions from CT Angiogram
47) Renal artery (RA) anatomy on either side or Common hepatic artery (CHA) anatomy, ineligible for treatment including the following:
a) CHA or RA diameter less than 4.0 mm or greater than 7.0 mm
b) CHA or RA length less than 20.0 mm
c) Only one functioning kidney
d) Presence of abnormal kidney tumors
e) CHA or RA with aneurysm
f) Pre-existing stent or history of angioplasty in target arteries
g) Fibromuscular dysplasia of the CHA or renal arteries
h) Presence of CHA or RA diameter stenosis greather than 30%
i) Individual lacks appropriate arterial anatomy for effective treatment or for maneuvering of the device from the femoral artery to the target location(s)

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive Statistics

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
23/01/2020
Actual
5/03/2020
Date of last participant enrolment
Anticipated
1/07/2023
Actual
Date of last data collection
Anticipated
1/07/2024
Actual
Sample size
Target
30
Accrual to date
17
Final
Recruitment outside Australia
Country [1] 21857 0
New Zealand
State/province [1] 21857 0

Funding & Sponsors
Funding source category [1] 303812 0
Commercial sector/Industry
Name [1] 303812 0
Metavention, Inc.
Country [1] 303812 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Metavention, Inc.
Address
10900 73rd Avenue North
Suite 101
Maple Grove, MN 55369
Country
United States of America
Secondary sponsor category [1] 303933 0
None
Name [1] 303933 0
Address [1] 303933 0
Country [1] 303933 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304327 0
New Zealand Northern B Health and Disabilities Ethics Committee
Ethics committee address [1] 304327 0
Ministry of Health
Health and Disabilities Ethics Committee
P.O. Box 5013
Wellington, NZ 6140
Ethics committee country [1] 304327 0
New Zealand
Date submitted for ethics approval [1] 304327 0
19/09/2019
Approval date [1] 304327 0
15/11/2019
Ethics approval number [1] 304327 0
19/NTB/164

Summary
Brief summary
Overactive SNS signaling to central metabolic organs, the kidneys and liver, can play a pivotal role in the development and progression of conditions associated with the MetS, including HTN and diabetes. Inhibition of this overactive sympathetic signaling, through intravascular denervation, is a proposed therapy to address these sympathetically mediated disorders. The purpose of the DeLIVER Study is to evaluate the safety of renal and hepatic denervation, in one procedure, using the Integrated Radio Frequency (iRF) Denervation System and to detect any improvement in controlling hypertension, blood sugar and other parameters involved in your metabolism following the denervation procedure.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96554 0
Dr Mark Webster
Address 96554 0
Consultant Interventional Cardiologist
Green Lane Cardiovascular Service
Auckland City Hospital
Private Bag 92-024
Park Road, Grafton
Auckland 1142
New Zealand
Country 96554 0
New Zealand
Phone 96554 0
+6493670000
Fax 96554 0
Email 96554 0
[email protected]
Contact person for public queries
Name 96555 0
Mr Adam Ahlstrom
Address 96555 0
Metavention, Inc
10900 73rd Avenue North
Country 96555 0
United States of America
Phone 96555 0
+1 612 814 8208
Fax 96555 0
Email 96555 0
[email protected]
Contact person for scientific queries
Name 96556 0
Dr Mark Webster
Address 96556 0
Consultant Interventional Cardiologist
Green Lane Cardiovascular Service
Auckland City Hospital
Private Bag 92-024
Park Road, Grafton
Auckland 1142
New Zealand
Country 96556 0
New Zealand
Phone 96556 0
+6493670000
Fax 96556 0
Email 96556 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
EmbaseExtra-cardiac targets in the management of cardiometabolic disease: Device-based therapies.2021https://dx.doi.org/10.1002/ehf2.13361
N.B. These documents automatically identified may not have been verified by the study sponsor.