TARGET BP I Clinical Trial (TARGET BP I)

• ClinicalTrials.gov Identifier: NCT02910414
• Recruitment Status: Active, not recruiting
• First Posted: September 22, 2016
• Last Update Posted: April 7, 2023
• Sponsor: Ablative Solutions, Inc.
• Information provided by (Responsible Party): Ablative Solutions, Inc.

Tracking Information

• First Submitted Date: September 16, 2016
• First Posted Date: September 22, 2016
• Last Update Posted Date: April 7, 2023
• Actual Study Start Date: July 22, 2019
• Estimated Primary Completion Date: August 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 5, 2019)

Change in mean systolic ABPM [ Time Frame: 3 months ]

The change in mean 24-hour ambulatory SBP from baseline to 3 months post-procedure

Original Primary Outcome Measures (submitted: September 20, 2016)

Change in mean systolic ABPM [ Time Frame: 8 weeks ]

The change in 24-hour mean systolic ambulatory blood pressure (ABPM) from baseline to 8 weeks

Current Secondary Outcome Measures (submitted: February 5, 2019)

• Proportion of subjects with major adverse events [ Time Frame: 30 days ]
  Major Adverse Events as defined in the clinical protocol
• Major Adverse Events [ Time Frame: 3, 6, and 12 months and 2 and 3 years ]
  Major Adverse Events as defined in the clinical protocol
• Decrease in eGFR > 25% [ Time Frame: 3 and 6 months ]
  Decrease in eGFR > 25% at 3 and 6 months
• Changes in eGFR [ Time Frame: 3 and 6 months ]
  Changes in eGFR at 3 and 6 months
• Adverse event rate [ Time Frame: 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 ]
  Adverse event rate at procedure, discharge, and at all follow-up visits
• Device success [ Time Frame: Procedure date (day 0) ]
  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 success [ Time Frame: Hospital discharge date (an average of 1 day) ]
  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.
• Change of office systolic blood pressure [ Time Frame: 8 weeks ]
  Change of office systolic blood pressure from baseline to 8 weeks
• Change of diastolic office blood pressure [ Time Frame: 3 and 6 months ]
  Change of diastolic office blood pressure from baseline to 3 and 6 months
• Change of 24-hour mean diastolic ABPM [ Time Frame: 3 and 6 months ]
  Change of 24-hour mean diastolic ABPM from baseline to 3 and 6 months
• Change of 24-hour mean systolic ABPM [ Time Frame: 6 months ]
  Change of 24-hour mean systolic ABPM from baseline to 6 months
• Changes in antihypertensive regimen [ Time Frame: 3 months ]
  Changes in antihypertensive regimen from procedure to 3 months post-procedure
• ABPM responders (5 mmHg) [ Time Frame: 3 months ]
  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.
• Office BP responders (10 mmHg) [ Time Frame: 3 months ]
  Office BP Responders, defined as the proportion of subjects with a drop of ≥10 mmHg in office SBP at 3 months compared with baseline.
• Change in mean office SBP [ Time Frame: 6 months ]
  Change in mean office SBP from baseline to 6 months post-procedure
• Change in mean daytime ambulatory SBP [ Time Frame: 3 months ]
  Change in mean daytime ambulatory SBP from baseline to 3 months post procedure.
• Change in mean daytime ambulatory SBP [ Time Frame: 6 months ]
  Change in mean daytime ambulatory SBP from baseline to 6 months post procedure.
• Change in mean daytime ambulatory DBP [ Time Frame: 3 and 6 months ]
  Change in mean daytime ambulatory DBP from baseline to 3 months and then 6 months post procedure.
• Changes (decreases or increases) in antihypertensive medication regimen from 3 months to 6 months post-procedure [ Time Frame: 3 and 6 months ]
  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).
• Changes (decreases or increases) in antihypertensive medication regimen from procedure to 6 months post-procedure [ Time Frame: 6 months ]
  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)
• Change in mean nighttime ambulatory SBP [ Time Frame: 3 and 6 months ]
  Change in mean nighttime ambulatory SBP from baseline to 3 months and then 6 months post procedure.
• Change in mean nighttime ambulatory DBP [ Time Frame: 3 and 6 months ]
  Change in mean nighttime ambulatory DBP from baseline to 3 months and then 6 months post procedure.
• Reduction of office SBP and DBP to normal [ Time Frame: 3, 6, and 12 months ]
  Reduction of office SBP and DBP to normal (<140/90 mmHg) at 3, 6 and 12 months as compared to baseline.

Original Secondary Outcome Measures (submitted: September 20, 2016)

• Major Adverse Events [ Time Frame: 30 days ]
  Major Adverse Events as defined in the clinical protocol
• Decrease in eGFR > 25% [ Time Frame: 8 weeks ]
  Decrease in eGFR > 25% at 8 weeks
• Changes in eGFR [ Time Frame: 8 weeks and 6 months ]
  Changes in eGFR at 8 weeks and 6 months
• Adverse event rate [ Time Frame: 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 ]
  Adverse event rate at procedure, discharge, and at all follow-up visits
• Device success [ Time Frame: Procedure date (day 0) ]
  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 success [ Time Frame: Hospital discharge date (an average of 1 day) ]
  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.
• Change of office systolic blood pressure [ Time Frame: 8 weeks ]
  Change of office systolic blood pressure from baseline to 8 weeks
• Change of diastolic office blood pressure [ Time Frame: 8 weeks ]
  Change of diastolic office blood pressure from baseline to 8 weeks
• Change of 24-hour mean diastolic ABPM [ Time Frame: 8 weeks ]
  Change of 24-hour mean diastolic ABPM from baseline to 8 weeks
• Changes in antihypertensive regimen [ Time Frame: 8 weeks ]
  Changes in antihypertensive regimen from treatment to 8 weeks
• Changes in antihypertensive regimen [ Time Frame: 6 months ]
  Changes in antihypertensive regimen from 8 weeks to 6 months
• ABPM responders (2 mmHg) [ Time Frame: 8 weeks ]
  ABPM Responders, defined as the proportion of subjects with a drop of greater than or equal to 2 mmHg in 24-hour ABPM systolic blood pressure at 8 weeks when compared to baseline
• Office BP responders (5 mmHg) [ Time Frame: 8 weeks ]
  Office BP Responders, defined as the proportion of subjects with a drop of greater than or equal to 5 mmHg in office-based systolic blood pressure at 8 weeks when compared to baseline
• ABPM responders (5 mmHg) [ Time Frame: 8 weeks ]
  ABPM Responders, defined as the proportion of subjects with a drop of greater than or equal to 5 mmHg in 24-hour ABPM systolic blood pressure at 8 weeks when compared to baseline
• Office BP responders (10 mmHg) [ Time Frame: 8 weeks ]
  Office BP Responders, defined as the proportion of subjects with a drop of greater than or equal to 10 mmHg in office-based systolic blood pressure at 8 weeks when compared to baseline

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: TARGET BP I Clinical Trial
• Official Title: A Pivotal, Multicenter, Blinded, Sham Procedure-Controlled Trial of Renal Denervation by the Peregrine System™ Kit, in Subjects With Hypertension
• Brief Summary: 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.

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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Hypertension

Intervention

• Drug: Dehydrated alcohol
  Dehydrated Alcohol Injection, USP is used in the study.
  Other Name: Ethanol
• Device: Peregrine System Kit (Sham Procedure)
  Pre-procedural diagnostic renal angiography only, performed for confirmation of anatomical eligibility prior to randomization

Study Arms

• 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.
  Intervention: Drug: Dehydrated alcohol
• 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).
  Intervention: Device: Peregrine System Kit (Sham Procedure)

• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 13, 2019): 300
• Original Estimated Enrollment (submitted: September 20, 2016): 100
• Estimated Study Completion Date: May 2026
• Estimated Primary Completion Date: August 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02910414
• Other Study ID Numbers: CR0002
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ablative Solutions, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Ablative Solutions, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: David Kandzari, MD; Piedmont Heart Institute
• 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

• PRS Account: Ablative Solutions, Inc.
• Verification Date: April 2023