Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension (WAVE_IV)
Primary Purpose
Hypertension
Status
Unknown status
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Investigational Therapy (Surround Sound)
Sham Control
Sponsored by

About this trial
This is an interventional treatment trial for Hypertension focused on measuring Hypertension, Renal Denervation
Eligibility Criteria
Inclusion Criteria:
- Subject is at least 18 years of age and no more than 90 years of age
- Average SBP ≥ 160 mmHg
- 24 hour average ABPM daytime SBP ≥ 135 mmHg.
- No medication changes for a minimum of 1 months prior to screening.
At minimum, subject must be on at least three antihypertensive medications, with one being a diuretic, and each must meet one or more of the following full dose criteria:
- Highest labeled dose according to medication's labeling;
- Highest usual dose per clinical guidelines JNC-7;
- Highest tolerated dose; and/or
- Highest appropriate dose for the subject per the PI's clinical judgment.
- Subject has two functioning kidneys.
- Subject has an eGFR value of ≥ 30 ml/min/1.73 m² (MDRD formula).
Exclusion Criteria:
- Subject has any secondary cause of hypertension
- Subject has evidence of clinically significant renal artery stenosis as determined by flow rate, velocity and Doppler analysis on ultrasound
- Subject has kidney stones that are of a size and location that are determined at discretion of the investigator to potentially interfere with treatment
- Subject has a history of intra-abdominal surgery within the past six months
- Subject has heterogeneities in the kidney such as large cysts or tumors that are determined at discretion of the investigator to potentially interfere with treatment.
- Stenotic valvular heart disease for which BP reduction would be hazardous as determined by referring physician.
- MI, unstable angina, or CVA in the prior 6 months.
- Known severe primary pulmonary HTN
- Subject has a history of myocardial infarction, unstable angina pectoris, or cerebrovascular accident within the last six months.
- Subject has hemodynamically significant valvular heart disease.
- Subject has BMI over 40 km/m^2
- Subject has a target treatment depth over 13 cm.
- Subject has anatomy that precludes treatment with the Kona Medical Surround Sound System.
- Subject is pregnant, nursing, or intends to become pregnant during the trial period.
- Subject is currently enrolled in other potentially confounding research.
- Subject has any condition that, at the discretion of the investigator, would preclude participation in the trial.
- Subject is unable, or unwilling, to comply with the protocol-required follow-up schedule
Sites / Locations
- Monash Medical Centre
- Medizinischen Universität Wien -UK für Klinische PharmakologieRecruiting
- Angiografia de Occidente, S.A.
- CHD Cardio Centro de Excelencia SAS
- St. Anne's University Hospital
- University Hospital Brno
- Městská Nomocnice Ostrava
- General University Hospital
- Nemocnice Na Homolee Hospital
- University Hospital BonnRecruiting
- University Hospital of the University of Erlangen-NurembergRecruiting
- CardioVascular Center Frankfurt - Sankt Katharinen HospitalRecruiting
- University Hospital Hamburg-EppendorfRecruiting
- Uniklinik KölnRecruiting
- Universitaetsklinikum LeipzigRecruiting
- Sana CardioMed NordRecruiting
- Deutsches Herzzentrum MuenchenRecruiting
- Clemens Hospital GmbHRecruiting
- Mercy Angiography
- Oddział Kliniczny II Kliniki KardiologiiRecruiting
- Institute Of CardiologyRecruiting
- Birmingham Heartlands HospitalRecruiting
- University Hospital WalesRecruiting
- Royal Devon and Exeter HospitalRecruiting
- University of GlasgowRecruiting
- St. Bartholomew's HospitalRecruiting
- University College London
- Southampton University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Investigational Therapy (Surround Sound)
Sham Control
Arm Description
Investigational Therapy using external focused ultrasound
Blinded Sham Control Arm
Outcomes
Primary Outcome Measures
Safety at 6 weeks follow-up
Safety will be assessed by incidence of Major Adverse Events (MAE), defined as a composite of the following events at 6-weeks follow-up.
All cause mortality;
End-stage Renal Disease defined as eGFR < 15 ml/min or need for renal replacement therapy
Hospitalization for hypertensive crisis not related to confirmed non-adherence with medications as assessed by toxicological and other medical analyses and testing.
OR
- New renal artery stenosis > 70% confirmed by angiography within 6 months of randomization
Change in OBP
Change in Office Systolic Blood Pressure (OBP) as measured from screening visit one to the 6 month post randomization follow-up visit.
Secondary Outcome Measures
Change in ABPM
Change in average 24-hour ambulatory blood pressure from screening to the 6 month follow-up visit
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02029885
Brief Title
Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension
Acronym
WAVE_IV
Official Title
Wave IV Study: Phase II Randomized Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Unknown status
Study Start Date
August 2014 (undefined)
Primary Completion Date
March 2016 (Anticipated)
Study Completion Date
March 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kona Medical Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To demonstrate that non-invasive renal denervation is safe and shows a net difference in blood pressure reduction when compared to sham in subjects with uncontrolled hypertension.
Detailed Description
This study is a sham controlled, double blind study of subjects with uncontrolled hypertension consisting of two arms, sham and therapy. Bilateral renal denervation will be performed non-invasively using the Kona Medical Surround Sound System which delivers focused ultrasound therapy to ablate the nerves surrounding the renal artery utilizing real time ultrasound for targeting and tracking.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension
Keywords
Hypertension, Renal Denervation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
132 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Investigational Therapy (Surround Sound)
Arm Type
Experimental
Arm Description
Investigational Therapy using external focused ultrasound
Arm Title
Sham Control
Arm Type
Sham Comparator
Arm Description
Blinded Sham Control Arm
Intervention Type
Device
Intervention Name(s)
Investigational Therapy (Surround Sound)
Intervention Type
Device
Intervention Name(s)
Sham Control
Primary Outcome Measure Information:
Title
Safety at 6 weeks follow-up
Description
Safety will be assessed by incidence of Major Adverse Events (MAE), defined as a composite of the following events at 6-weeks follow-up.
All cause mortality;
End-stage Renal Disease defined as eGFR < 15 ml/min or need for renal replacement therapy
Hospitalization for hypertensive crisis not related to confirmed non-adherence with medications as assessed by toxicological and other medical analyses and testing.
OR
- New renal artery stenosis > 70% confirmed by angiography within 6 months of randomization
Time Frame
6 weeks
Title
Change in OBP
Description
Change in Office Systolic Blood Pressure (OBP) as measured from screening visit one to the 6 month post randomization follow-up visit.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Change in ABPM
Description
Change in average 24-hour ambulatory blood pressure from screening to the 6 month follow-up visit
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Chronic Safety
Description
Chronic safety is assessed and compared between the control and treatment groups at 6 months post-randomization as follows:
Cardiovascular/Renal Death;
End stage Renal Disease
Increase in serum creatinine of > 50%; and
Hospitalization for hypertensive crisis not confirmed non-adherence with medications.
Time Frame
6 months
Title
Reduction in blood pressure
Description
Reduction in systolic and diastolic blood pressure as compared between groups at time points through the 6 month follow-up period for interval differences of 10,15 and 20 mmHg.
Time Frame
6 months
Title
Incidence of achieving target OBP
Description
Incidence of achieving target OBP (< 140 mmHg) through the 6 month follow-up period.
Time Frame
6 months
Title
Reduction in anti-hypertensive medications
Description
Incidence of reductions in the number of anti-hypertensive medications and reductions in the doses of anti-hypertensive medications.
Time Frame
6 months
Title
Changes in OBP
Description
Changes in OBP from screening to the 12, 18, and 24 month follow-up periods.
Time Frame
24 months
Title
Changes in HR
Description
Changes in HR (as measured by OBP and ABPM) through the 6 month follow-up period.
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject is at least 18 years of age and no more than 90 years of age
Average SBP ≥ 160 mmHg
24 hour average ABPM daytime SBP ≥ 135 mmHg.
No medication changes for a minimum of 1 months prior to screening.
At minimum, subject must be on at least three antihypertensive medications, with one being a diuretic, and each must meet one or more of the following full dose criteria:
Highest labeled dose according to medication's labeling;
Highest usual dose per clinical guidelines JNC-7;
Highest tolerated dose; and/or
Highest appropriate dose for the subject per the PI's clinical judgment.
Subject has two functioning kidneys.
Subject has an eGFR value of ≥ 30 ml/min/1.73 m² (MDRD formula).
Exclusion Criteria:
Subject has any secondary cause of hypertension
Subject has evidence of clinically significant renal artery stenosis as determined by flow rate, velocity and Doppler analysis on ultrasound
Subject has kidney stones that are of a size and location that are determined at discretion of the investigator to potentially interfere with treatment
Subject has a history of intra-abdominal surgery within the past six months
Subject has heterogeneities in the kidney such as large cysts or tumors that are determined at discretion of the investigator to potentially interfere with treatment.
Stenotic valvular heart disease for which BP reduction would be hazardous as determined by referring physician.
MI, unstable angina, or CVA in the prior 6 months.
Known severe primary pulmonary HTN
Subject has a history of myocardial infarction, unstable angina pectoris, or cerebrovascular accident within the last six months.
Subject has hemodynamically significant valvular heart disease.
Subject has BMI over 40 km/m^2
Subject has a target treatment depth over 13 cm.
Subject has anatomy that precludes treatment with the Kona Medical Surround Sound System.
Subject is pregnant, nursing, or intends to become pregnant during the trial period.
Subject is currently enrolled in other potentially confounding research.
Subject has any condition that, at the discretion of the investigator, would preclude participation in the trial.
Subject is unable, or unwilling, to comply with the protocol-required follow-up schedule
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Omar Dawood
Email
odawood@konamedical.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roland Schmieder, MD
Organizational Affiliation
University Hospital of University of Erlangen-Nuremberg
Official's Role
Principal Investigator
Facility Information:
Facility Name
Monash Medical Centre
City
Clayton
Country
Australia
Individual Site Status
Terminated
Facility Name
Medizinischen Universität Wien -UK für Klinische Pharmakologie
City
Vienna
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Wolzt, MD
Facility Name
Angiografia de Occidente, S.A.
City
Cali
Country
Colombia
Individual Site Status
Terminated
Facility Name
CHD Cardio Centro de Excelencia SAS
City
Cali
Country
Colombia
Individual Site Status
Terminated
Facility Name
St. Anne's University Hospital
City
Brno
Country
Czech Republic
Individual Site Status
Active, not recruiting
Facility Name
University Hospital Brno
City
Brno
Country
Czech Republic
Individual Site Status
Active, not recruiting
Facility Name
Městská Nomocnice Ostrava
City
Ostrava
Country
Czech Republic
Individual Site Status
Active, not recruiting
Facility Name
General University Hospital
City
Prague
Country
Czech Republic
Individual Site Status
Withdrawn
Facility Name
Nemocnice Na Homolee Hospital
City
Prague
Country
Czech Republic
Individual Site Status
Active, not recruiting
Facility Name
University Hospital Bonn
City
Bonn
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Georg Nickenig, MD
Facility Name
University Hospital of the University of Erlangen-Nuremberg
City
Erlangen
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sabine Thuemmler
Email
sabine.thuemmler@uk-erlangen.de
First Name & Middle Initial & Last Name & Degree
Roland Schmieder, MD
Facility Name
CardioVascular Center Frankfurt - Sankt Katharinen Hospital
City
Frankfurt
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Horst Sievert, MD
Facility Name
University Hospital Hamburg-Eppendorf
City
Hamburg
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ulrich Wenzel Oberarzt, MD
Phone
+49(40) 7410-50026
Email
wenzel@uke.de
First Name & Middle Initial & Last Name & Degree
Ulrich Wenzel Oberarzt, MD
Facility Name
Uniklinik Köln
City
Koln
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tatjana Schewior
Phone
+49 (221) 478 88273
Email
tatjana.schewior@uk-koeln.de
First Name & Middle Initial & Last Name & Degree
Hannes Reuter
Facility Name
Universitaetsklinikum Leipzig
City
Leipzig
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ursula Banning-Eichenseer
Phone
+49 341 9720657
Email
ursula.banning-eichenseer@med.uni-leipzig.de
First Name & Middle Initial & Last Name & Degree
Dierk Scheinert, MD
Facility Name
Sana CardioMed Nord
City
Luebeck
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anke Constantz
Phone
+49 451 585 1951
Email
anke.constantz@sana.de
First Name & Middle Initial & Last Name & Degree
Joachim Weil, MD
Facility Name
Deutsches Herzzentrum Muenchen
City
Munich
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ilka Ott, MD
Phone
+49 (89) 1218-4578
Email
ott@dhm.mhn.de
First Name & Middle Initial & Last Name & Degree
Ilka Ott, MD
Facility Name
Clemens Hospital GmbH
City
Münster
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Baumgart, MD
Facility Name
Mercy Angiography
City
Aukland
Country
New Zealand
Individual Site Status
Active, not recruiting
Facility Name
Oddział Kliniczny II Kliniki Kardiologii
City
Krakow
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dariusz Dudek, MD
Phone
+48 12 42 47 181
Email
mcdudek@cyfronet.pl
First Name & Middle Initial & Last Name & Degree
Dariusz Dudek, MD, PhD
Facility Name
Institute Of Cardiology
City
Warsaw
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adam Witkowski, MD
Phone
+48 22 34 34 127
Email
witkowski@hbz.pl
First Name & Middle Initial & Last Name & Degree
Adam Witkowski, MD, PhD
Facility Name
Birmingham Heartlands Hospital
City
Birmingham
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Indranil Desgupta, MD, DM, FRCP
Facility Name
University Hospital Wales
City
Cardiff
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
James Coulson, MD
Phone
+44 (0) 7968 366691
Email
coulsonjm@cardiff.ac.uk
First Name & Middle Initial & Last Name & Degree
James Coulson, MD
Facility Name
Royal Devon and Exeter Hospital
City
Exeter
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew Sharp, MD
Email
andrew.sharp5@nhs.net
First Name & Middle Initial & Last Name & Degree
Andrew Sharp, MD
Facility Name
University of Glasgow
City
Glasgow
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alan Jardine
Facility Name
St. Bartholomew's Hospital
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mel Lobo, PhD
Phone
+44 (0) 7780 700440
Email
m.d.lobo@qmul.ac.uk
First Name & Middle Initial & Last Name & Degree
Mel Lobo, MD, PhD
Facility Name
University College London
City
London
Country
United Kingdom
Individual Site Status
Withdrawn
Facility Name
Southampton University Hospital
City
Southampton
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
James Wilkinson
Phone
+44 (0) 7931 703058
Email
james.wilkinson@uhs.nhs.uk
First Name & Middle Initial & Last Name & Degree
James Wilkinson, PhD FRCP
12. IPD Sharing Statement
Citations:
PubMed Identifier
29895590
Citation
Saxena M, Shour T, Shah M, Wolff CB, Julu POO, Kapil V, Collier DJ, Ng FL, Gupta A, Balawon A, Pheby J, Zak A, Rull G, O'Brien B, Schmieder RE, Lobo MD. Attenuation of Splanchnic Autotransfusion Following Noninvasive Ultrasound Renal Denervation: A Novel Marker of Procedural Success. J Am Heart Assoc. 2018 Jun 12;7(12):e009151. doi: 10.1161/JAHA.118.009151.
Results Reference
derived
Learn more about this trial
Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension
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