Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension (WAVE_IV)

Wave IV Study: Phase II Randomized Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension

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.

Study Overview

• Status: Unknown
• Conditions: Hypertension
• Intervention / Treatment: Device: Sham Control; Device: Investigational Therapy (Surround Sound)

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.

• Study Type: Interventional
• Enrollment (Anticipated): 132
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Clayton, Australia
    • Terminated
    • Monash Medical Centre
• Austria
  • Vienna, Austria
    • Recruiting
    • Medizinischen Universität Wien -UK für Klinische Pharmakologie
    • Principal Investigator: Michael Wolzt, MD
• Colombia
  • Cali, Colombia
    • Terminated
    • Angiografia de Occidente, S.A.
  • Cali, Colombia
    • Terminated
    • CHD Cardio Centro de Excelencia SAS
• Czech Republic
  • Brno, Czech Republic
    • Active, not recruiting
    • St. Anne's University Hospital
  • Brno, Czech Republic
    • Active, not recruiting
    • University Hospital Brno
  • Ostrava, Czech Republic
    • Active, not recruiting
    • Městská Nomocnice Ostrava
  • Prague, Czech Republic
    • Withdrawn
    • General University Hospital
  • Prague, Czech Republic
    • Active, not recruiting
    • Nemocnice Na Homolee Hospital
• Germany
  • Bonn, Germany
    • Recruiting
    • University Hospital Bonn
  • Erlangen, Germany
    • Recruiting
    • University Hospital of the University of Erlangen-Nuremberg
    • Contact: Sabine Thuemmler; Email: sabine.thuemmler@uk-erlangen.de
    • Principal Investigator: Roland Schmieder, MD
  • Frankfurt, Germany
    • Recruiting
    • CardioVascular Center Frankfurt - Sankt Katharinen Hospital
  • Hamburg, Germany
    • Recruiting
    • University Hospital Hamburg-Eppendorf
    • Contact: Ulrich Wenzel Oberarzt, MD; Phone Number: +49(40) 7410-50026; Email: wenzel@uke.de
    • Principal Investigator: Ulrich Wenzel Oberarzt, MD
  • Koln, Germany
    • Recruiting
    • Uniklinik Köln
    • Contact: Tatjana Schewior; Phone Number: +49 (221) 478 88273; Email: tatjana.schewior@uk-koeln.de
    • Principal Investigator: Hannes Reuter
  • Leipzig, Germany
    • Recruiting
    • Universitaetsklinikum Leipzig
    • Contact: Ursula Banning-Eichenseer; Phone Number: +49 341 9720657; Email: ursula.banning-eichenseer@med.uni-leipzig.de
  • Luebeck, Germany
    • Recruiting
    • Sana CardioMed Nord
    • Contact: Anke Constantz; Phone Number: +49 451 585 1951; Email: anke.constantz@sana.de
  • Munich, Germany
    • Recruiting
    • Deutsches Herzzentrum Muenchen
    • Contact: Ilka Ott, MD; Phone Number: +49 (89) 1218-4578; Email: ott@dhm.mhn.de
  • Münster, Germany
    • Recruiting
    • Clemens Hospital GmbH
    • Principal Investigator: Peter Baumgart, MD
• New Zealand
  • Aukland, New Zealand
    • Active, not recruiting
    • Mercy Angiography
• Poland
  • Krakow, Poland
    • Recruiting
    • Oddział Kliniczny II Kliniki Kardiologii
    • Contact: Dariusz Dudek, MD; Phone Number: +48 12 42 47 181; Email: mcdudek@cyfronet.pl
  • Warsaw, Poland
    • Recruiting
    • Institute of Cardiology
    • Contact: Adam Witkowski, MD; Phone Number: +48 22 34 34 127; Email: witkowski@hbz.pl
• United Kingdom
  • Birmingham, United Kingdom
    • Recruiting
    • Birmingham Heartlands Hospital
    • Principal Investigator: Indranil Desgupta, MD, DM, FRCP
  • Cardiff, United Kingdom
    • Recruiting
    • University Hospital Wales
    • Contact: James Coulson, MD; Phone Number: +44 (0) 7968 366691; Email: coulsonjm@cardiff.ac.uk
    • Principal Investigator: James Coulson, MD
  • Exeter, United Kingdom
    • Recruiting
    • Royal Devon and Exeter Hospital
    • Contact: Andrew Sharp, MD; Email: andrew.sharp5@nhs.net
    • Principal Investigator: Andrew Sharp, MD
  • Glasgow, United Kingdom
    • Recruiting
    • University of Glasgow
    • Principal Investigator: Alan Jardine
  • London, United Kingdom
    • Recruiting
    • St. Bartholomew's Hospital
    • Contact: Mel Lobo, PhD; Phone Number: +44 (0) 7780 700440; Email: m.d.lobo@qmul.ac.uk
    • Principal Investigator: Mel Lobo, MD, PhD
  • London, United Kingdom
    • Withdrawn
    • University College London
  • Southampton, United Kingdom
    • Recruiting
    • Southampton University Hospital
    • Contact: James Wilkinson; Phone Number: +44 (0) 7931 703058; Email: james.wilkinson@uhs.nhs.uk
    • Principal Investigator: James Wilkinson, PhD FRCP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject is at least 18 years of age and no more than 90 years of age
2. Average SBP ≥ 160 mmHg
3. 24 hour average ABPM daytime SBP ≥ 135 mmHg.
4. No medication changes for a minimum of 1 months prior to screening.

5. 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:

   1. Highest labeled dose according to medication's labeling;
   2. Highest usual dose per clinical guidelines JNC-7;
   3. Highest tolerated dose; and/or
   4. Highest appropriate dose for the subject per the PI's clinical judgment.
6. Subject has two functioning kidneys.
7. Subject has an eGFR value of ≥ 30 ml/min/1.73 m² (MDRD formula).

Exclusion Criteria:

1. Subject has any secondary cause of hypertension
2. Subject has evidence of clinically significant renal artery stenosis as determined by flow rate, velocity and Doppler analysis on ultrasound
3. Subject has kidney stones that are of a size and location that are determined at discretion of the investigator to potentially interfere with treatment
4. Subject has a history of intra-abdominal surgery within the past six months
5. 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.
6. Stenotic valvular heart disease for which BP reduction would be hazardous as determined by referring physician.
7. MI, unstable angina, or CVA in the prior 6 months.
8. Known severe primary pulmonary HTN
9. Subject has a history of myocardial infarction, unstable angina pectoris, or cerebrovascular accident within the last six months.
10. Subject has hemodynamically significant valvular heart disease.
11. Subject has BMI over 40 km/m^2
12. Subject has a target treatment depth over 13 cm.
13. Subject has anatomy that precludes treatment with the Kona Medical Surround Sound System.
14. Subject is pregnant, nursing, or intends to become pregnant during the trial period.
15. Subject is currently enrolled in other potentially confounding research.
16. Subject has any condition that, at the discretion of the investigator, would preclude participation in the trial.
17. Subject is unable, or unwilling, to comply with the protocol-required follow-up schedule

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational Therapy (Surround Sound); Investigational Therapy using external focused ultrasound	Device: Investigational Therapy (Surround Sound)
Sham Comparator: Sham Control; Blinded Sham Control Arm	Device: Sham Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	6 weeks
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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ABPM	Change in average 24-hour ambulatory blood pressure from screening to the 6 month follow-up visit	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chronic Safety	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.	6 months
Reduction in blood pressure	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.	6 months
Incidence of achieving target OBP	Incidence of achieving target OBP (< 140 mmHg) through the 6 month follow-up period.	6 months
Reduction in anti-hypertensive medications	Incidence of reductions in the number of anti-hypertensive medications and reductions in the doses of anti-hypertensive medications.	6 months
Changes in OBP	Changes in OBP from screening to the 12, 18, and 24 month follow-up periods.	24 months
Changes in HR	Changes in HR (as measured by OBP and ABPM) through the 6 month follow-up period.	6 months

Collaborators and Investigators

• Sponsor: Kona Medical Inc.
• Investigators: Principal Investigator: Roland Schmieder, MD, University Hospital of University of Erlangen-Nuremberg

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Anticipated): March 1, 2016
• Study Completion (Anticipated): March 1, 2018

Study Registration Dates

• First Submitted: January 6, 2014
• First Submitted That Met QC Criteria: January 6, 2014
• First Posted (Estimate): January 8, 2014

Study Record Updates

• Last Update Posted (Estimate): January 8, 2016
• Last Update Submitted That Met QC Criteria: January 6, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Hypertension; Renal Denervation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: KM14-001