TARGET BP I Clinical Trial (TARGET BP I)

A Pivotal, Multicenter, Blinded, Sham Procedure-Controlled Trial of Renal Denervation by the Peregrine System™ Kit, in Subjects With Hypertension

The TARGET BP I Trial is a randomized, blinded, multi-center, international, sham-procedure controlled trial, comparing renal denervation performed with the Peregrine System Kit in the treatment group to the sham control group (without renal denervation - no alcohol infusion). Subjects will be randomized in a 1:1 fashion to treatment versus sham control via central randomization.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypertension
• Intervention / Treatment: Drug: Dehydrated alcohol; Device: Peregrine System Kit (Sham Procedure)

Detailed Description

The TARGET BP I Trial is a randomized, blinded, multi-center, international, sham-procedure controlled trial, comparing renal denervation performed with the Peregrine System Kit in the treatment group to the sham control group (without renal denervation - no alcohol infusion). Subjects will be randomized in a 1:1 fashion to treatment versus sham control via central randomization.

The TARGET BP I clinical trial uses a percutaneous catheter to deliver very small amounts of alcohol (neurolytic agent). The patient population for this trial is comparable to those used in other renal denervation studies, but also incorporates lessons learned from recent trials of renal denervation. This is to enable the study of an optimized patient population who stands to benefit from the intervention, in a manner that reduces possible study bias.

This trial is intended to evaluate the safety and efficacy of the Peregrine Catheter when used to deliver a 0.6 mL volume of alcohol to the perivascular area of the respective renal arteries while patients are adequately managed with oral antihypertensive medications.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Kristine Canavan; Phone Number: +1 (650) 688-9743; Email: kcanavan@ablativesolutions.com
• Study Contact Backup: Name: Debbie Reynolds, PhD; Phone Number: +1 (650) 688-9743; Email: dreynolds@ablativesolutions.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Cardiology PC
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Heart Institute
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • NC Heart and Vascular Research
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Has 3 office blood pressure measurements with a mean office systolic blood pressure (SBP) of ≥150 mmHg and ≤180 mmHg, AND a mean office diastolic blood pressure (DBP) of ≥90 mmHg when receiving 2 to 5 antihypertensive medications.
2. Has a mean 24-hour ambulatory SBP of ≥135 mmHg and ≤170 mmHg with ≥70% valid readings

Exclusion Criteria:

1. Subject has renal artery anatomy abnormalities.
2. Subject has an estimated glomerular filtration rate (eGFR) of ≤45 mL/min/1.73 m2, based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation; or is on chronic renal replacement therapy.
3. Subject has documented sleep apnea.
4. Subject has any of the following conditions: severe cardiac valve stenosis, heart failure (New York Heart Association [NYHA] Class III or IV), chronic atrial fibrillation, and known primary pulmonary hypertension (>60 mmHg pulmonary artery or right ventricular systolic pressure).
5. Subject is pregnant or lactating at the time of enrollment or planning to become pregnant during the trial time period (female subjects only).
6. Subject is being treated chronically (e.g. daily use) with NSAIDs, immunosuppressive medications, or immunosuppressive doses of steroids. Aspirin therapy and nasal pulmonary inhalants are allowed.
7. Subject has a history of myocardial infarction, unstable angina pectoris, or stroke/TIA within 6 months prior to the planned procedure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treated with Peregrine System Kit; The experimental group will receive an infusion of Dehydrated Alcohol Injection, USP into the perivascular space of the renal arteries with the Peregrine Catheter. A total of 0.6mL of the alcohol will be delivered to the perivascular space of each renal artery. The drug will only be delivered once to each renal artery during the treatment procedure.	Drug: Dehydrated alcohol; Dehydrated Alcohol Injection, USP is used in the study.; Other Names: Ethanol
Sham Comparator: Renal Angiography Only (Sham Procedure); The sham control group will only have diagnostic renal angiography performed. There will be no insertion of the Peregrine Catheter and no alcohol infusion (i.e. no renal denervation).	Device: Peregrine System Kit (Sham Procedure); Pre-procedural diagnostic renal angiography only, performed for confirmation of anatomical eligibility prior to randomization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mean systolic ABPM	The change in mean 24-hour ambulatory SBP from baseline to 3 months post-procedure	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with major adverse events	Major Adverse Events as defined in the clinical protocol	30 days
Major Adverse Events	Major Adverse Events as defined in the clinical protocol	3, 6, and 12 months and 2 and 3 years
Decrease in eGFR > 25%	Decrease in eGFR > 25% at 3 and 6 months	3 and 6 months
Changes in eGFR	Changes in eGFR at 3 and 6 months	3 and 6 months
Adverse event rate	Adverse event rate at procedure, discharge, and at all follow-up visits	Procedure date, discharge date (an average of 1 day), 5-day, 4 weeks, 8 weeks, 3 months, 4 months, 5 months, 6 months, 1 year, 2 years and 3 years
Device success	Device success, defined as successful introduction of the catheter, navigation to the treatment site, deployment of the needles, and infusion of the alcohol to the intended area via the Peregrine Catheter as intended for use	Procedure date (day 0)
Procedure success	Procedure success defined as device success and freedom from serious adverse events related to the product or the procedure, during the procedure and prior to hospital discharge from the index procedure.	Hospital discharge date (an average of 1 day)
Change of office systolic blood pressure	Change of office systolic blood pressure from baseline to 8 weeks	8 weeks
Change of diastolic office blood pressure	Change of diastolic office blood pressure from baseline to 3 and 6 months	3 and 6 months
Change of 24-hour mean diastolic ABPM	Change of 24-hour mean diastolic ABPM from baseline to 3 and 6 months	3 and 6 months
Change of 24-hour mean systolic ABPM	Change of 24-hour mean systolic ABPM from baseline to 6 months	6 months
Changes in antihypertensive regimen	Changes in antihypertensive regimen from procedure to 3 months post-procedure	3 months
ABPM responders (5 mmHg)	ABPM Responders, defined as the proportion of subjects with a drop of ≥5 mmHg in 24-hour ambulatory SBP at 3 months compared with baseline.	3 months
Office BP responders (10 mmHg)	Office BP Responders, defined as the proportion of subjects with a drop of ≥10 mmHg in office SBP at 3 months compared with baseline.	3 months
Change in mean office SBP	Change in mean office SBP from baseline to 6 months post-procedure	6 months
Change in mean daytime ambulatory SBP	Change in mean daytime ambulatory SBP from baseline to 3 months post procedure.	3 months
Change in mean daytime ambulatory SBP	Change in mean daytime ambulatory SBP from baseline to 6 months post procedure.	6 months
Change in mean daytime ambulatory DBP	Change in mean daytime ambulatory DBP from baseline to 3 months and then 6 months post procedure.	3 and 6 months
Changes (decreases or increases) in antihypertensive medication regimen from 3 months to 6 months post-procedure	Changes (decreases or increases) in antihypertensive medication regimen from 3 months to 6 months post-procedure (titrated according to standardized formula to maintain a target office SBP of < 140 mmHg and ≥ 90 mmHg).	3 and 6 months
Changes (decreases or increases) in antihypertensive medication regimen from procedure to 6 months post-procedure	Changes (decreases or increases) in antihypertensive medication regimen from procedure to 6 months post-procedure (titrated according to standardized formula to maintain a target office SBP of <140 mmHg and ≥90 mmHg)	6 months
Change in mean nighttime ambulatory SBP	Change in mean nighttime ambulatory SBP from baseline to 3 months and then 6 months post procedure.	3 and 6 months
Change in mean nighttime ambulatory DBP	Change in mean nighttime ambulatory DBP from baseline to 3 months and then 6 months post procedure.	3 and 6 months
Reduction of office SBP and DBP to normal	Reduction of office SBP and DBP to normal (<140/90 mmHg) at 3, 6 and 12 months as compared to baseline.	3, 6, and 12 months

Collaborators and Investigators

• Sponsor: Ablative Solutions, Inc.
• Investigators: Principal Investigator: Michael Weber, MD, SUNY Downstate Medical; Principal Investigator: Atul Pathak, MD, Clinique Pasteur; Principal Investigator: Felix Mahfoud, MD, Klinik fur Innere Medizin III; Principal Investigator: David Kandzari, MD, Piedmont Heart Institute

Publications and helpful links

General Publications

• Bertog S, Sharma A, Mahfoud F, Pathak A, Schmieder RE, Sievert K, Papademetriou V, Weber MA, Haratani N, Lobo MD, Saxena M, Kandzari DE, Fischell TA, Sievert H. Alcohol-Mediated Renal Sympathetic Neurolysis for the Treatment of Hypertension: The Peregrine Infusion Catheter. Cardiovasc Revasc Med. 2021 Mar;24:77-86. doi: 10.1016/j.carrev.2020.09.003. Epub 2020 Sep 7.

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2019
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: September 16, 2016
• First Submitted That Met QC Criteria: September 20, 2016
• First Posted (Estimated): September 22, 2016

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Alcohol; Renal Denervation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Ethanol
• Other Study ID Numbers: CR0002

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: Yes
• Studies a U.S. FDA-regulated device product: Yes