Evaluation of Renal Denervation via Ethanol-Mediated Neurolysis Using the Peregrine System™ Kit in Patients with Uncontrolled Hypertension
- Trial ID
- 2024-512525-83-00
- Protocol
- CR0002
- Sponsor
- Ablative Solutions Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of renal denervation by alcohol-mediated neurolysis using the Peregrine Kits in subjects with uncontrolled **hypertension** when used in combination with antihypertensive medications. This is clinically relevant as it aims to determine the potential of this intervention to effectively manage blood pressure in patients who do not achieve adequate control with medication alone.
Secondary objectives include:
- Evaluating the acute and chronic **safety** of renal denervation by alcohol-mediated neurolysis using the Peregrine Kits in combination with antihypertensive medications.
- Assessing the sustained efficacy of this procedure in the same patient population.
- Evaluating the performance of the Peregrine Kits, which is a co-packaged combination of alcohol and the Peregrine Systems, for its intended use.
Participants
The clinical trial involves a total of **938 participants** diagnosed with **hypertension**. The study population includes both male and female subjects, aged between 18 and 80 years. Participants are required to be on a regimen of 2 to 5 antihypertensive medications, with specific requirements regarding the types and dosages of these medications. The trial population was selected based on their uncontrolled hypertensive status despite medication, with a mean office systolic blood pressure (SBP) of 150-180 mmHg and a diastolic blood pressure (DBP) of at least 90 mmHg. Participants must maintain a stable medication regimen and meet specific blood pressure criteria throughout the study. The trial includes individuals who are able to comply with study procedures and follow-up visits, and female participants of childbearing potential must use acceptable contraception methods. The study does not exclude vulnerable populations, indicating a broad inclusion of individuals who meet the specified criteria.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **renal denervation** by alcohol-mediated neurolysis using the Peregrine System™ Kit in subjects with **hypertension**. This is a pivotal, multicenter, blinded, sham procedure-controlled trial. The trial employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The estimated duration of the trial is from February 18, 2020, to September 30, 2025, with participant involvement expected to last approximately 12 months from the procedure date.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, including age, medication regimen, and blood pressure levels. Following the screening, there is a 4-week run-in period during which participants must maintain a stable antihypertensive medication regimen. The procedure visit will involve the administration of the investigational product, a **solution for injection** containing ethanol, anhydrous, delivered perivascularly using the Peregrine System™ Infusion Catheter. This catheter is a percutaneous device with microneedles for precise delivery.
Post-procedure, participants will have follow-up visits at 3, 6, and 12 months to monitor changes in blood pressure and any adjustments in antihypertensive medication. The primary endpoint is the change in mean 24-hour ambulatory systolic blood pressure (SBP) from baseline to 3 months post-procedure. Secondary endpoints include changes in mean office SBP and diastolic blood pressure (DBP) at various intervals, as well as the assessment of major adverse events and renal artery stenosis.
Participants may be terminated early from the study if they experience significant adverse events, fail to adhere to the medication regimen, or withdraw consent. The trial aims to provide comprehensive data on the safety and efficacy of the Peregrine System™ Kit in managing hypertension, contributing to the understanding of renal denervation as a therapeutic option.
Treatment
The clinical trial involves the use of the **Peregrine System™ Kit**, which is an experimental treatment designed for renal denervation in subjects with hypertension. The active substance in this treatment is **ethanol, anhydrous**, which is of chemical origin. The pharmaceutical form of the Peregrine System™ Kit is a **solution for injection**. The administration route is **perivascular**, and the maximum daily dose is 2.4 ml, with the same amount being the maximum total dose. The treatment period is limited to a single day. The Peregrine System™ Kit is not a pediatric formulation and is not classified as an orphan drug. The solution is administered using the Peregrine System™ Infusion Catheter, a percutaneous catheter equipped with three distal microneedles that are deployed via a control handle. This device has received a CE mark, indicating compliance with European health, safety, and environmental protection standards.
In addition to the experimental treatment, the study includes a sham procedure-controlled group to serve as a comparator. This group will undergo a procedure that mimics the experimental treatment without the administration of the active substance, ensuring that any observed effects can be attributed to the ethanol-mediated neurolysis. Participants in both groups will continue to receive standard-of-care antihypertensive medications as part of their treatment regimen. Compliance with the dosing schedule and administration procedures will be closely monitored throughout the trial to ensure adherence to the protocol and to accurately assess the efficacy and safety of the experimental treatment.
Efficacy
The efficacy of the renal denervation procedure using the Peregrine System™ Kit in subjects with **hypertension** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the change in mean 24-hour ambulatory systolic blood pressure (SBP) from baseline to 3 months post-procedure. Secondary endpoints include changes in mean office SBP and diastolic blood pressure (DBP) at various time points, such as 4 weeks, 3 months, and 6 months post-procedure. Additionally, changes in antihypertensive medication regimens and the proportion of subjects achieving specific blood pressure reductions will be evaluated.
Measurements will be collected using validated ambulatory blood pressure monitoring (ABPM) devices and office blood pressure measurements. The schedule for these assessments includes baseline, 4 weeks, 3 months, and 6 months post-procedure, with further evaluations at 12 months and beyond. The trial will also monitor major adverse events (MAEs) and changes in estimated glomerular filtration rate (eGFR) to assess safety alongside efficacy. The success of the procedure will be determined by the ability to perform the renal denervation without complications, as well as achieving the intended blood pressure reductions.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Prior to run-in period : Subject has provided written informed consent.
- Prior to run-in period : Male or female subject, aged ≥18 and ≤80 years at time of enrollment.
- Prior to run-in period : Subject is taking 2-5 antihypertensive medications (labeled for hypertension) at time of enrollment, and is willing to adhere to a stable (no change) medication regimen during the 4-week run-in period and 3 months post-procedure. Antihypertensive medications must be as follows: Two of the antihypertensive medications must be at least at 50% of their maximally labelled dose prior to the planned procedure; In subjects on 2 medications, one should be an ACE inhibitor or ARB, except where subjects have documented intolerance to each of these drug classes. All subjects must currently be taking, or have documentation that they failed or cannot tolerate, a diuretic. In the case of the thiazide agents hydrochlorothiazide and chlorthalidone, 12.5 mg would be acceptable as a minimum dose when used in combination with one or more other antihypertensive medications. For subjects on 2 non-diuretic antihypertensive medications, because they either failed or have been unable to tolerate a diuretic, the 2 medications should consist of any of the classes of antihypertensive agents listed below, with the preferred choice of an ACE inhibitor or ARB and a CCB. In the latter case, if both ACE inhibitor/ARB and CCB are contraindicated or not tolerated, such reasons must be documented. Note: The following classes of antihypertensive agents that would count towards the minimum number of agents are: ACE inhibitors, ARBs, CCBs, thiazide diuretics, loop diuretics, aldosterone antagonists, beta-blockers, centrally active agents, alpha receptor blockers, direct vasodilators, direct renin inhibitors, and hydralazine.
- Prior to run-in period : Subject meets blood pressure criteria at time of enrollment and prior to the 4-week run-in period: has 3 office blood pressure measurements with a mean office SBP of ≥150 mmHg and ≤180 mmHg, AND a mean office DBP ≥90 mmHg.
- Prior to run-in period : Investigator judges that the subject can be managed safely during the 4-week run-in period and 3 months post-procedure period without any changes to their current antihypertensive medication regimen.
- Prior to run-in period : Female subjects of childbearing potential must agree to use acceptable methods of contraception (as defined in the protocol), from the time of informed consent through to the last follow-up visit.
- Prior to run-in period : Subject agrees to have all study procedures performed and is able and willing to comply with all study follow-up visits and protocol requirements.
- End of run-in period : Subject has maintained the same antihypertensive medication regimen for at least 4 weeks (28 days) prior to the procedure.
- End of run-in period : Subject meets blood pressure criteria: Has 3 office blood pressure measurements with a mean office SBP of ≥ 150 mmHg and ≤180 mmHg AND mean office DBP ≥90 mmHg AND Has a mean 24-hour ambulatory SBP of ≥135 mmHg and ≤170 mmHg with ≥70% valid readings (as determined by ABPM measurement device)
Exclusion Criteria
- Subject has documented severe untreated obstructive sleep apnea (apnea-hypopnea index [AHI] ≥30 per hour).
- Subject has documented diagnosis of the following causes of hypertension: Cushing's disease or Cushing's Syndrome, hyperaldosteronism, pheochromocytoma, thyroid and parathyroid abnormalities, or onset of hypertension prior to the age of 18.
- Subject has a history of pre-eclampsia within the 5 years prior to study entry.
- Subject has orthostatic hypotension at baseline, or documented history of orthostatic hypotension within 12 months prior to the planned procedure, defined as a drop in blood pressure that is >20 mmHg in SBP and/or >10 mmHg in DBP within 3 minutes upon standing from sitting or from a lying down face-up (supine) position.
- Any contraindication to the imaging as required per the protocol.
- Subject has imaging-assessed renal artery anatomy abnormalities or variations based on investigator's evaluation of the screening images (i.e. MRA/CTA examination) meeting one of the following criteria: • Main renal artery that has a diameter of <3 mm or >7 mm and length of <5 mm • Accessory renal arteries with diameter <3mm, which supply >20% of the whole kidney parenchyma on that side, per the investigator's judgment • Subjects with more than one accessory renal artery per side supplying >20% of the whole kidney parenchyma. • Renal artery stenosis >50% of the normal diameter segment • Any renal artery abnormality or disease that, per the physician assessment, precludes the safe insertion of the guiding catheter • Previous renal angioplasty associated with stenting or other implants, that, per the physician's assessment, precludes the safe deployment of the Peregrine Catheter components in the target treatment segment of the renal artery • Previous renal denervation • Fibromuscular dysplasia of the renal arteries
- Subject has a renal transplant, or is known to have a non-functioning kidney or unequal renal size (>2 cm difference in renal length between kidneys associated with a chronic kidney disease or a deterioration of the kidney function).
- Subject has a history of nephrectomy, a single kidney or kidney tumor, or urinary tract obstruction (with potential for hydronephrosis). Note: Simple renal cysts are not an exclusion.
- Subject has a history of recurrent (>1 episode) kidney stones, or history of kidney stones within 12 months prior to the planned procedure.
- Subject has an 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 nephrotic syndrome
- Subject for whom an ABPM device cannot be used due to arm size (>42 cm arm circumference) or other reasons as identified by the investigator.
- Subject has any of the following conditions: severe cardiac valve stenosis, heart failure (New York Heart Association [NYHA] Class III or IV), atrial fibrillation (defined as at least one documented episode in the 12 months before study entry), or known primary pulmonary hypertension (>60 mmHg pulmonary artery or right ventricular systolic pressure).
- Subject has an acute or sub-acute infection that the investigator judges would pose unacceptable procedural risks to the subject
- Subject has Type 1 diabetes mellitus, or uncontrolled Type 2 diabetes mellitus (defined as hemoglobin A1c [HbA1c] ≥9.0%).
- Subject has a contraindication known for conventional percutaneous interventional procedures such as: • Intolerance for antiplatelet/anticoagulant therapy • Known hypersensitivity to contrast media that cannot be adequately pre-medicated • Bleeding/coagulation disorders (such as bleeding diathesis, thrombocytopenia, and severe anemia). • Occlusive peripheral vascular disease that would preclude percutaneous femoral access for the procedure
- Subject has a known hypersensitivity to the neurolytic agent (i.e. dehydrated alcohol).
- Subject has a known history of substance (drug) use or alcohol dependence, or lacks the ability to comprehend or follow instructions, or for any reason, in the opinion of the investigator, would be unlikely or unable to comply with study protocol requirements.
- Subject is being treated chronically (e.g. daily use) with nonsteroidal anti-inflammatory drugs (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/transient ischemic attack (TIA) within 6 months prior to the planned procedure.
- If female, subject is pregnant or lactating at the time of enrollment or planning to become pregnant during the trial time period.
- Subject has any other acute or chronic condition that the investigator believes will adversely affect the ability to interpret the data or will prevent the subject from completing the trial procedures, or has a life expectancy of <12 months.
- Subject is participating or has participated in another clinical study involving an investigational drug or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational drug or investigational device during the course of this study. Subjects enrolled in observational registries not involving renal denervation may still be eligible.
- Subject is in custody or in an institution.
- Subject has close affiliation with the study site or sponsor (e.g., Principal Investigator, Study Nurse, sponsor employee, close relative of study personnel or sponsor employee).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Recruiting | 18 Feb 2020 | 39 |
 Belgium | Not Recruiting | 18 Feb 2020 | 63 |
 France | Not Recruiting | 18 Feb 2020 | 41 |
 Germany | Not Recruiting | 18 Feb 2020 | 176 |
 Ireland | Not Recruiting | 18 Feb 2020 | 40 |
 The Netherlands | Not Recruiting | 18 Feb 2020 | — |
 Poland | Not Recruiting | 18 Feb 2020 | 54 |
| Netherlands | — | — | 52 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Peregrine System™ Kit | Test | SOLUTION FOR INJECTION | PERIVASCULAR | 2.4 | 1 | PRD6415283 |