Hypertension, Hypertension,Essential
Conditions
Keywords
Renal denervation, Neurolysis
Brief summary
To obtain an assessment of the efficacy and safety of renal denervation by dehydrated alcohol injection, USP administered via the Peregrine System™ Infusion Catheter in hypertensive subjects in the absence of antihypertensive medications.
Detailed description
This Phase 3, prospective, randomized, blinded, sham procedure-controlled, multicenter study will assess the efficacy and safety of renal denervation by alcohol-mediated neurolysis using the Peregrine Catheter in hypertensive subjects in the absence of antihypertensive medications. Subjects with a documented history of uncontrolled hypertension who are taking 0, 1, or 2 antihypertensive medications at enrollment will be recruited. After providing written informed consent, subjects will undergo screening assessments to assess eligibility for the study. Eligible subjects will then enter a run-in period during which they will take no antihypertensive medications. Subjects who continue to be eligible at the end of the run-in period will complete the study Baseline visit and remain without taking antihypertensive medications. Subjects who continue to be eligible after the completion of the Baseline visit will attend the study site and will be randomized to either the Treatment Arm (renal denervation using the Peregrine Catheter) or the Sham Control Arm (renal angiography only). After study unblinding, crossover from the Sham Control Arm to the Treatment Arm may be allowed, at the discretion of the treating investigator.
Interventions
DRUGDehydrated Alcohol Injection, USP
Alcohol is directly infused/delivered to the adventitial and periadventitial space of the renal arteries
PROCEDURESham procedure
Endovascular, renal angiography
Sponsors
Ablative Solutions, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Treatment arm: renal denervation performed with dehydrated alcohol injection, USP administered via the Peregrine System™ Infusion Catheter. Sham Control Arm: only renal angiography performed
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Has 2 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. 2. Documented history of uncontrolled hypertension and is currently taking 0, 1, or 2 antihypertensive medications. 3. Is willing to discontinue any current antihypertensive medications for at least 13 weeks (5-week pre-procedure and 8-week post-procedure). 4. Has a mean 24-hour ambulatory SBP of ≥140 mmHg and ≤170 mmHg with required valid readings.
Exclusion criteria
1. Has renal artery anatomy abnormalities. 2. Has previously undergone renal denervation. 3. 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. 4. Has documented untreated sleep apnea. 5. Has any of the following conditions: severe cardiac valve stenosis, heart failure (New York Heart Association \[NYHA\] Class III or IV), chronic atrial fibrillation (defined as at least one documented episode in the 12 months before study entry), and known primary pulmonary hypertension (\>60 mmHg pulmonary artery or right ventricular systolic pressure). 6. Is pregnant or lactating at the time of enrollment or planning to become pregnant during the trial time period (female subjects only). 7. 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. 8. Has a history of myocardial infarction, unstable angina pectoris, or stroke/TIA within 6 months prior to the planned procedure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Systolic Ambulatory Blood Pressure at 8 weeks | Baseline to 8 weeks post-treatment | Change from baseline in mean 24-hour ambulatory systolic blood pressure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Office SBP at 8 Weeks | Baseline to 8 weeks post-treatment | Change from Baseline in mean office SBP to Week 8 |
| Change in Office DBP at 8 Weeks | Baseline to 8 weeks post-treatment | Change from Baseline in mean office DBP to Week 8 |
| Changes in Diastolic Ambulatory Blood Pressure at 8 Weeks | Baseline to 8 weeks post-treatment | Change from baseline in mean 24-hour ambulatory diastolic blood pressure at 8 weeks post-procedure |
| Changes in Systolic Ambulatory Blood Pressure at 6 Months | Baseline to 6 months post-treatment | Change from baseline in mean 24-hour ambulatory systolic blood pressure at 6 months post-procedure |
| Changes in Diastolic Ambulatory Blood Pressure at 6 Months | Baseline to 6 months post-treatment | Change from baseline in mean 24-hour ambulatory diastolic blood pressure at 6 months post-procedure |
| Changes in Mean Daytime Ambulatory SBP at 8 Weeks | Baseline to 8 weeks post-treatment | Change from baseline in mean daytime systolic blood pressure at 8 weeks post-procedure |
| Changes in Mean Daytime Ambulatory SBP at 6 Months | Baseline to 6 months post-treatment | Change from baseline in mean daytime systolic blood pressure at 6 months post-procedure |
| Changes in Mean Daytime Ambulatory DBP at 8 Weeks | Baseline to 8 weeks post-treatment | Change from baseline in mean daytime diastolic blood pressure at 8 weeks post-procedure |
| Changes in Mean Daytime Ambulatory DBP at 6 Months | Baseline to 6 months post-treatment | Change from baseline in mean daytime diastolic blood pressure at 6 months post-procedure |
| Changes in Mean Nighttime Ambulatory SBP at 8 Weeks | Baseline to 8 weeks post-treatment | Change from baseline in mean nighttime systolic blood pressure at 8 weeks post-procedure |
| Changes in Mean Nighttime Ambulatory SBP at 6 Months | Baseline to 6 months post-treatment | Change from baseline in mean nighttime systolic blood pressure at 6 months post-procedure |
| Changes in Mean Nighttime Ambulatory DBP at 8 Weeks | Baseline to 8 weeks post-treatment | Change from baseline in mean nighttime diastolic blood pressure at 8 weeks post-procedure |
| Changes in Mean Nighttime Ambulatory DBP at 6 Months | Baseline to 6 months post-treatment | Change from baseline in mean nighttime DBP at 6 months post-procedure |
| Change in Office SBP at 6 Months | Baseline to 6 months post-treatment | Change from Baseline in mean office SBP at 6 months post-procedure |
| Change in Office DBP at 6 Months | Baseline to 6 months post-treatment | Change from Baseline in mean office DBP to Week 8 at 6 months post-procedure |
| Use of Antihypertensive Medication(s) at 8 Weeks | 8 weeks post-treatment | Use of antihypertensive medication at 8 weeks post-procedure |
| Use of antihypertensive medication(s) from 8 Weeks to 6 Months | 6 months post-treatment | Change in use of antihypertensive medication(s) from 8 Weeks to 6 Months post procedure (titrated according to standardized formula to maintain a target SBP of \<140 mmHg and ≥90 mmHg) |
| Number of Participants With Major Adverse Events (MAEs) | 30 days post-treatment | Number of participants with major adverse events (MAEs) 30 days post-procedure |
| Change in Home SBP at 8 Weeks | 8 weeks post-treatment | Change from Baseline in mean home SBP at 8 weeks post-procedure |
| Change in Home SBP at 6 months | 6 months post-treatment | Change from Baseline in mean home SBP at 6 months post-procedure |
| Change in Home DBP at 8 Weeks | 8 weeks post-treatment | Change from Baseline in mean home DBP at 8 weeks post-procedure |
| Change in Home DBP at 6 months | 6 months post-treatment | Change from Baseline in mean home DBP at 6 months post-procedure |
Countries
United States
Contacts
CONTACTMissy Broich
CONTACTDebbie Reynolds, PhD
STUDY_CHAIRMichael Weber, MD
SUNY Downstate Medical Center and College of Medicine
STUDY_CHAIRDavid Kandzari, MD
Piedmont Healthcare
STUDY_CHAIRFelix Mahfoud, Prof.Dr. med
University of Basel
STUDY_CHAIRAtul Pathak, Prof.
Princess Grace Hospital, Monaco
PRINCIPAL_INVESTIGATORGregg Stone, MD
The Mount Sinai Hospital
Outcome results
None listed