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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Ablative Solutions, Inc.
Sponsor:
Information provided by (Responsible Party):
Ablative Solutions, Inc.
ClinicalTrials.gov Identifier:
NCT02155790
First received: May 27, 2014
Last updated: May 4, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention
Hypertension
Device: The Peregrine System Infusion Catheter

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Safety and Performance Study of Renal Denervation by Neurolysis Using the Ablative Solutions Inc. Peregrine System™ Infusion Catheter

Resource links provided by NLM:


Further study details as provided by Ablative Solutions, Inc.:

Primary Outcome Measures:
  • Vessel dissection or perforation [ Time Frame: Immediate post procedure ] [ Designated as safety issue: Yes ]
    Vessel dissection or perforation on immediate post-procedural fluoroscopy

  • Grade 3 or Grade 4 hemorrhage [ Time Frame: During or immediately after procedure ] [ Designated as safety issue: Yes ]
    Grade 3 hemorrhage requiring transfusion or Grade 4 hemorrhage

  • Cerebrovascular accident [ Time Frame: Time of procedure ] [ Designated as safety issue: Yes ]
    Cerebrovascular accident at the time of procedure

  • Myocardial infarction [ Time Frame: Time of procedure ] [ Designated as safety issue: Yes ]
    Myocardial infarction at the time of the procedure

  • Sudden cardiac death [ Time Frame: Time of procedure ] [ Designated as safety issue: Yes ]
    Sudden cardiac death at the time of the procedure

  • Reduction in the systolic blood pressure [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The primary performance endpoint is a reduction in the clinic systolicand diastolic blood pressure following treatment compared to baseline, assessed at 6 months.


Secondary Outcome Measures:
  • Change in eGFR (reduction >25%) [ Time Frame: baseline to 6 months ] [ Designated as safety issue: Yes ]
    Proportion of patients with a decline in eGFR by >25% from baseline to 6 months follow-up

  • New renal arterial stenosis >60% [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    New renal arterial stenosis >60% from baseline confirmed by the same method used at baseline

  • Mean change in serum creatinine [ Time Frame: post baseline visits at 7d,1 mo,3mo,6mo,12mo,24mo ] [ Designated as safety issue: Yes ]
    Change in serum creatinine

  • Adverse events [ Time Frame: post baseline visits at 7d,1 mo,3mo,6mo,12mo,24moprocedure and each of the follow-up time periods ] [ Designated as safety issue: Yes ]
    Adverse events - device and non-device related

  • Changes in antihypertensive medications [ Time Frame: post baseline visits at 7d,1 mo,3mo,6mo,12mo,24moeach of the follow-up visits ] [ Designated as safety issue: No ]

    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.


  • Changes in ambulatory blood pressure measurements [ Time Frame: post baseline visits at 7d,1 mo,3mo,6mo,12mo,24mo ] [ Designated as safety issue: No ]
    Ambulatory blood pressures will be reported to determine if they follow a similar patter to the clinic blood pressures.


Estimated Enrollment: 50
Study Start Date: July 2014
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Renal denervation using a neurolytic agent

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02155790

Contacts
Contact: Wojciech Wojakowski, Prof.MD.PhD +48 (604) 188 669 wojtek.wojakowski@gmail.com

Locations
Czech Republic
Na Homolce Hospital Recruiting
Prague, Czech Republic, 15030
Contact: Dana Veselá, Mgr.    +42 257272 ext 391    dana.vesela@homolka.cz   
Contact: Jitka Hofmanová       jitka.hofmanova@homolka.cz   
Principal Investigator: Petr Neuzil, Prof.MUDr         
Poland
American Heart of Poland Recruiting
Tychy, Poland
Contact: Adam Janas, MD.PhD    +48 322279826    adamjjanas@gmail.com   
Contact: Bartlomeiej Orlik, MD.PhD    +48 609523231    orlik.bartek@gmail.com   
Principal Investigator: Mariusz Hochul, MD.PhD         
Sub-Investigator: Wojciech Wojakowski, Prof.MD.PhD         
Sub-Investigator: Janas Adam, MD.PhD         
Sub-Investigator: Orlik Bartlomiej, MD.PhD         
American Heart of Poland Recruiting
Ustron, Poland, 43-450
Contact: Wojciech Wojakowski, Prof.MD.PhD    +48 604 188 669    wojtek.wojakowski@gmail.com   
Principal Investigator: Wojciech Wojakowski, Prof.MD.PhD         
Sponsors and Collaborators
Ablative Solutions, Inc.
Investigators
Principal Investigator: Wojciech Wojakowski, Prof.MD.PhD American Hospitals Poland
  More Information

No publications provided

Responsible Party: Ablative Solutions, Inc.
ClinicalTrials.gov Identifier: NCT02155790     History of Changes
Other Study ID Numbers: ASI 12-001
Study First Received: May 27, 2014
Last Updated: May 4, 2015
Health Authority: Poland: Main Pharmaceutical Inspectorate
Czech Republic: State Institute for Drug Control

Keywords provided by Ablative Solutions, Inc.:
safety, performance, hypertension, renal denervation

ClinicalTrials.gov processed this record on May 21, 2015