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

• ClinicalTrials.gov Identifier: NCT02029885
• Recruitment Status: Unknown
• First Posted: January 8, 2014
• Last Update Posted: January 8, 2016
• Sponsor: Kona Medical Inc.
• Information provided by (Responsible Party): Kona Medical Inc.

Tracking Information

• First Submitted Date: January 6, 2014
• First Posted Date: January 8, 2014
• Last Update Posted Date: January 8, 2016
• Study Start Date: August 2014
• Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 11, 2014)

• Safety at 6 weeks follow-up [ Time Frame: 6 weeks ]
  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 [ Time Frame: 6 months ]
  Change in Office Systolic Blood Pressure (OBP) as measured from screening visit one to the 6 month post randomization follow-up visit.

Original Primary Outcome Measures (submitted: January 6, 2014)

Safety at 3 weeks follow-up [ Time Frame: 3 weeks ]

Safety will be assessed by incidence of Major Adverse Events (MAE), defined as a composite of the following events at 3-weeks follow-up.

Current Secondary Outcome Measures (submitted: June 11, 2014)

Change in ABPM [ Time Frame: 6 months ]

Change in average 24-hour ambulatory blood pressure from screening to the 6 month follow-up visit

Original Secondary Outcome Measures (submitted: January 6, 2014)

Efficacy [ Time Frame: 24 months ]

Long term performance (efficacy) is evaluated by comparing the change in Office Systolic blood pressure from screening through the 24-month evaluation

Current Other Pre-specified Outcome Measures (submitted: June 11, 2014)

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

Original Other Pre-specified Outcome Measures (submitted: January 6, 2014)

Long term Safety [ Time Frame: 24 months ]

Chronic safety is assessed by incidence and evaluation by any serious adverse events associated with the Kona Medical Surround Sound non-invasive system through the 24 week follow-up period

Descriptive Information

• Brief Title: Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension
• Official Title: Wave IV Study: Phase II Randomized Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension
• 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.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Hypertension

Intervention

• Device: Investigational Therapy (Surround Sound)
• Device: Sham Control

Study Arms

• Experimental: Investigational Therapy (Surround Sound)
  Investigational Therapy using external focused ultrasound
  Intervention: Device: Investigational Therapy (Surround Sound)
• Sham Comparator: Sham Control
  Blinded Sham Control Arm
  Intervention: Device: Sham Control

• 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). pii: e009151. doi: 10.1161/JAHA.118.009151.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: September 23, 2014): 132
• Original Estimated Enrollment (submitted: January 6, 2014): 50
• Estimated Study Completion Date: March 2018
• Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Colombia, Czech Republic, Germany, New Zealand, Poland, United Kingdom

Administrative Information

• NCT Number: NCT02029885
• Other Study ID Numbers: KM14-001
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Kona Medical Inc.
• Study Sponsor: Kona Medical Inc.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Roland Schmieder, MD; University Hospital of University of Erlangen-Nuremberg

• PRS Account: Kona Medical Inc.
• Verification Date: January 2016