TARGET BP I Clinical Trial

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Dehydrated alcohol
* Device: Peregrine System Kit (Sham Procedure)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Has a mean 24-hour ambulatory SBP of ≥135 mmHg and ≤170 mmHg with ≥70% valid readings Exclusion Criteria: Subject has renal artery anatomy abnormalities. 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. Subject has documented sleep apnea. 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). Subject is pregnant or lactating at the time of enrollment or planning to become pregnant during the trial time period (female subjects only). 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. Subject has a history of myocardial infarction, unstable angina pectoris, or stroke/TIA within 6 months prior to the planned procedure.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treated with Peregrine System Kit<br>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<br>* Dehydrated Alcohol Injection, USP is used in the study.<br>* Other names: Ethanol;|
| Sham Comparator: Renal Angiography Only (Sham Procedure)<br>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)<br>* Pre-procedural diagnostic renal angiography only, performed for confirmation of anatomical eligibility prior to randomization<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal Denervation, Alcohol