First-In-Human Study Evaluating a Novel Catheter Device in Subjects With Treatment-Resistant Hypertension

First-In-Human Study for Ultrasound Based Endovascular Carotid Body Ablation in Subjects With Treatment-Resistant Hypertension: A Safety and Feasibility Study

The carotid body is located at the bifurcation of the internal and external carotid arteries. It is a chemoreceptor that plays a role in the sympathetic nervous system and in the development and maintenance of hypertension. Hypertension is a major cardiovascular risk factor and is associated with coronary artery disease, stroke, chronic kidney disease, and heart failure.

The objective of this study is to assess the effectiveness and safety of a catheter-based system to ablate the carotid body and reduce blood pressure (BP) in patients with resistant hypertension and to confirm sustainability of the treatment benefits long-term as seen following surgical CB removal.

Study Overview

• Status: Unknown
• Conditions: Hypertension,Essential
• Intervention / Treatment: Device: Catheter-Based Carotid Body Ablation

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• Czechia
  • Prague, Czechia, 15030
    • Na Homolce Hospital
• Germany
  • Bad Krozingen, Germany
    • Clinic Cardiology and Angiology II
  • Frankfurt, Germany, 60389
    • Cardiovascular Center Frankfurt (CVC Frankfurt)
  • Homburg, Germany, 66421
    • Klinik fur Innere Medizin III

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Mean office SBP ≥160 mmHg and DBP ≥90 mmHg during screen-in period
• Mean daytime systolic ABPM ≥135 mmHg during screen-in period
• Adherent to a stable drug regimen of three (3) or more anti-hypertensive medications of different classes (including one (1) diuretic), with no medication changes expected for at least six (6) months post-procedure
• No change in anti-hypertensive drug prescription (dose, number of medications, or class of medication) for at least six (6) weeks prior to enrollment
• Negative pregnancy test for women of child-bearing age
• Willingness and able to comply with follow-up requirements
• Signed informed consent

Exclusion Criteria:

• Secondary causes of hypertension
• Calculated eGFR <30mL/min/1.73m2
• History of repeated episodes of hypoglycemic unawareness
• Morbid obesity, defined as Body Mass Index >40 kg/m2
• Severe obstructive sleep apnea (AHI > 35/hr.)
• Pacemaker and/or implantable defibrillators
• History of transient ischemic accident or cerebrovascular accident during six (6) months prior to screening
• History of acute heart failure, congestive heart failure (NYHA class III-IV), myocardial infarction, unstable angina, coronary bypass or coronary angioplasty during six (6) months prior to screening
• History of ipsilateral carotid endarterectomy treatment or ipsilateral carotid artery stenting

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Catheter-Based Carotid Body Ablation; All subjects undergo catheter-based ablation of the carotid body using the Cibiem Transvenous Ultrasound System (CTUS).

Device: Catheter-Based Carotid Body Ablation; The Cibiem Transvenous Ultrasound System (CTUS) is a catheter based device delivering ultrasound energy to ablate the carotid body. The procedure is done via a percutaneous insertion of the CTUS and advancement through the femoral vein to the jugular vein in subjects with difficult to control hypertension. The procedure duration is expected to range between 60 to 90 minutes and is performed under fluoroscopic and ultrasound image guidance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as assessed by incidence of major adverse events	Safety assessed as the combined rate of major adverse events defined as all-causes of death, hospitalization for hypertensive crisis not related to confirmed non-adherence with anti-hypertensive medications, and any device or procedure-related serious adverse event.	From procedure to one month post-procedure
Mean reduction in 24-hour ambulatory systolic and diastolic blood pressure		Baseline versus six months post-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite rate of major adverse events	Safety assessed as the combined rate of major adverse events defined as all-causes of death and hospitalization for hypertensive crisis not related to confirmed non-adherence with anti-hypertensive medications	At 6, 12, 18, and 24 months post-procedure
Mean reduction in office systolic and diastolic blood pressure, and home systolic and diastolic blood pressure		Baseline versus 3, 6, 12, 18, and 24 months
Proportion of subjects with controlled blood pressure at 6, 12, 18, and 24 months post-procedure	Controlled blood pressure is defined as office blood pressure <140/90 mmHg, mean 24-hr ABP <130/80 mmHg, daytime ABP <135/85 mmHg, and mean nighttime ABP <120/70 mmHg	At 6, 12, 18, and 24 months
Ventricular morphometric improvements from cardiac MRI measurements		Screening versus 12 and 24 months

Collaborators and Investigators

• Sponsor: Cibiem, Inc.
• Investigators: Principal Investigator: Markus Schlaich, Professor, Royal Perth Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2015
• Primary Completion (Anticipated): August 1, 2018
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: October 15, 2017
• First Submitted That Met QC Criteria: October 15, 2017
• First Posted (Actual): October 19, 2017

Study Record Updates

• Last Update Posted (Actual): April 10, 2018
• Last Update Submitted That Met QC Criteria: April 6, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension
• Other Study ID Numbers: CL1008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes