The Peregrine Study: A Safety and Performance Study of Renal Denervation

A Safety and Performance Study of Renal Denervation by Neurolysis Using the Ablative Solutions Inc. Peregrine System™ Infusion Catheter

The Ablative Solutions, Inc. Peregrine System Infusion Catheter is a catheter-based device which is intended to be used to ablate the afferent and efferent sympathetic nerves serving the kidneys. The catheter is typically inserted via the femoral artery, steered into the renal artery, and then delivers, by infusion from its distal end, a neurolytic agent. This targets the nerve bundles, which are in the adventitia - a sheath surrounding the artery. The aim is to reduce blood pressure in cases of resistant hypertension - seriously elevated blood pressure which does not respond to drug treatment.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Device: The Peregrine System Infusion Catheter

Detailed Description

There is strong evidence in the published literature that the renal nerves are important contributors to hypertension, and that their ablation does not have adverse side-effects. The literature provides technical, clinical and scientific evidence supporting the use of perivascular renal denervation for a carefully defined patient group.

An existing device (the Ardian Symplicity catheter) has been shown to be safe and effective for achieving perivascular renal denervation by delivery of radiofrequency energy. Perivascular renal denervation by radio-frequency energy delivery is an effective therapy, associated with very low risks. In other contexts, denervation can also be safely and effectively achieved by neurolytic agents.

The objectives of the study are to evaluate the safety and performance of renal denervation by a chemical neurolytic agent delivered into the advential/ periadventitial area of the renal arteries for the purpose of neurolysis, using the Peregrine System Infusion Catheter, in patients with refractory hypertension.

The ASI Peregrine System Infusion Catheter is similar enough to the Ardian Symplicity catheter to enable the use of published data to establish the validity of the design concept of the Peregrine System and estimate the likely levels of risk from side effects. It can be concluded from the literature that the ASI Peregrine System will achieve percutaneous renal denervation with a low risk of procedural complications (comparable to accepted percutaneous interventional therapies) and without long-term impairment of renal artery or kidney function or other serious adverse events.

Chemical denervation is an appropriate treatment for the specified study population of adults who have resistant hypertension despite taking at least 3 anti-hypertensive drugs of different classes including at least one diuretic. In order for the study to be valid, only one chemical neurolytic agent can be used. The Coordinating Investigator has chosen to use dehydrated alcohol (96 - 98% by volume) for therapeutic neurolysis, therefore all participating sites will use this agent. This clinical investigation is intended to provide clinical data that demonstrates the safety and performance of the ASI Peregrine System Infusion Catheter.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia, 15030
    • Na Homolce Hospital
• Poland
  • Tychy, Poland
    • American Heart of Poland
  • Ustron, Poland, 43-450
    • American Heart of Poland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult patient, age 18-75, male or female;
2. Patient has a clinic systolic blood pressure ≥ 160 mm Hg (or ≥ 150 mm Hg in type 2 diabetic patients) based on an average of 3 office/clinic measurements taken manually;
3. Patient has a daytime mean systolic pressure ≥135 mm Hg based on 24 hours ambulatory blood pressure monitoring, with >85% valid readings.
4. Patient with resistant hypertension is receiving and adhering to a stable medication regimen of at least 3 anti-hypertensive medications of different classes (for at least 4 weeks), one of which must be a diuretic. The three (or more) - medication regimen must be maximal in terms of dose and tolerability in the judgement of the investigator, such that the next step in blood pressure management would be the addition of a further medication.
5. Patient has an eGFR ≥ 45 mL/min, based on the CKD-EPI equation;
6. Patient has no implanted ICD, pacemaker or neurostimulator or any metallic implant which is not compatible with magnetic resonance imaging. THis is applicable to sites were MRI is planned. Implanted devices are acceptable at sites where CT will be used

7. Patient has optimal renal artery anatomy (no clear abnormalities) based on Investigator's evaluation of CT-angiogram/ or as alternative MR-angiogram and /or renal angiogram including:

   • Single or two renal arteries, if each has a 5-7 mm diameter, respectively (accessory renal arteries are acceptable if diameter is is ≤ 2 mm, which will not be treated)
   • No aneurysms
   • No excessive tortuosity
   • No previous stenting or balloon angioplasty of the renal arteries
   • No previous renal denervation;
8. Patient has provided written informed consent

Exclusion Criteria:

1. Patient has known or suspected secondary hypertension;
2. Patient has type 1 diabetes mellitus;
3. Patient requires chronic oxygen support;
4. Patient has primary or secondary pulmonary hypertension;
5. Patient has a known bleeding diathesis.
6. Patient has thrombocytopenia (platelet count <100,000 platelets/µL;
7. Patient is pregnant or nursing or planning to become pregant;
8. Patient has significant imaging-assessed renovascular abnormalities including short length main renal artery (< 10mm) and renal artery stenosis >60% of the normal diameter segment;
9. Patient has history of nephrectomy, a single kidney, kidney tumor or urinary tract obstruction (with potential for hydronephrosis);
10. Patient is known to have a unilateral non-functioning kidney or unequal renal size (>2 cm difference in renal length between kidneys);
11. Patient has a renal transplant;
12. Patient has a history of kidney stones;
13. Patient has a history of heterogeneities in the kidney such as cysts or tumors;
14. Patient has a history of pyelonephritis;
15. Patient has a history of myocardial infarction, unstable angina pectoris, or cerebrovascular accident within the last six months;
16. Patient has hemodynamically significant valvular heart disease;
17. Patient has heart failure (NYHA III or IV) or has an ejection fraction ≤ 30%;
18. Patient has a known allergy to contrast media;
19. Patient has a life expectancy of <12 months;
20. Patient is currently enrolled in other potentially confounding research, i.e., another therapeutic or interventional research trial. Patients enrolled in observational registries may still be eligible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Renal Denervation by Neurolysis; Infusion of 0.3 ml of dehydrated alcohol (96%-98%) into the peri-adventitial space of the renal artery, to achieve renal denervation by Neurolysis, via three simultaneous deployed needles, situated at the distal end of the Peregrine System Infusion Catheter.	Device: The Peregrine System Infusion Catheter; The ASI catheter is inserted bilaterally into the renal arteries and a specified amount of a neurolytic agent is inserted into the vessel walls.; Other Names: Renal denervation using a neurolytic agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vessel dissection or perforation	Vessel dissection or perforation on immediate post-procedural fluoroscopy	Immediate post procedure
Grade 3 or Grade 4 hemorrhage	Grade 3 hemorrhage requiring transfusion or Grade 4 hemorrhage	During or immediately after procedure
Cerebrovascular accident	Cerebrovascular accident at the time of procedure	Time of procedure
Myocardial infarction	Myocardial infarction at the time of the procedure	Time of procedure
Sudden cardiac death	Sudden cardiac death at the time of the procedure	Time of procedure
Reduction in the systolic blood pressure	The primary performance endpoint is a reduction in the clinic systolicand diastolic blood pressure following treatment compared to baseline, assessed at 6 months.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in eGFR (reduction >25%)	Proportion of patients with a decline in eGFR by >25% from baseline to 6 months follow-up	baseline to 6 months
New renal arterial stenosis >60%	New renal arterial stenosis >60% from baseline confirmed by the same method used at baseline	6 months
Mean change in serum creatinine	Change in serum creatinine	post baseline visits at 7d,1 mo,3mo,6mo,12mo,24mo
Adverse events	Adverse events - device and non-device related	post baseline visits at 7d,1 mo,3mo,6mo,12mo,24moprocedure and each of the follow-up time periods
Changes in antihypertensive medications	The addition of new antihypertensive drugs will be considered an intensification of the antihypertensive regimen. Discontinuation of one or more of the baseline antihypertensive medications without an increase in dose of remaining drugs or addition of new drugs will be considered a reduction in antihypertensive drug regimen.	post baseline visits at 7d,1 mo,3mo,6mo,12mo,24moeach of the follow-up visits
Changes in ambulatory blood pressure measurements	Ambulatory blood pressures will be reported to determine if they follow a similar patter to the clinic blood pressures.	post baseline visits at 7d,1 mo,3mo,6mo,12mo,24mo

Collaborators and Investigators

• Sponsor: Ablative Solutions, Inc.
• Investigators: Principal Investigator: Wojciech Wojakowski, Prof.MD.PhD, American Hospitals Poland

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): September 4, 2017

Study Registration Dates

• First Submitted: May 27, 2014
• First Submitted That Met QC Criteria: June 2, 2014
• First Posted (Estimate): June 4, 2014

Study Record Updates

• Last Update Posted (Actual): June 14, 2018
• Last Update Submitted That Met QC Criteria: June 13, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: safety, performance, hypertension, renal denervation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: ASI 12-001