Hypertension
Conditions
Brief summary
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 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 hypertension, including seriously elevated blood pressure which does not respond to drug treatment. This study will evaluate the safety and performance of the device.
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 Medtronic Symplicity catheter) was initially shown to be safe and effective for achieving perivascular renal denervation by delivery of radio-frequency energy. The results of early nonrandomized clinical studies (HTN-1, HTN-2) found that perivascular renal denervation by radio-frequency energy delivery was an effective therapy, associated with very low risks. In other contexts, denervation can also be safely and effectively achieved by neurolytic agents. The ASI Peregrine System™ Infusion Catheter and the denervation procedure in general is similar enough to the Medtronic 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 of 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. Previous premarket clinical trials have provided support for the safe and effective use of the Peregrine Catheter for the treatment of patients with hypertension. The Peregrine System Infusion Catheter is currently CE marked and the indication for use is The Peregrine System™ Infusion Catheter is intended for the infusion of a neurolytic agent to achieve a reduction in systemic blood pressure in hypertensive patients. Based upon the literature and previous clinical data, chemical denervation is an appropriate treatment for the specified study population of adults who have hypertension despite taking at least 3 anti-hypertensive drugs of different classes including at least one diuretic. The objectives of this post-market study are to collect additional safety and performance data pertaining to renal denervation by using dehydrated alcohol as a chemical neurolytic agent delivered into the adventitial/peri-adventitial area of the renal arteries for the purpose of renal denervation, using the Peregrine System™ Infusion Catheter, in patients with hypertension. 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 (not less than 95% by volume) for therapeutic neurolysis, therefore all participating sites will use this agent.
Interventions
DEVICEPeregrine System Infusion Catheter
The Peregrine Catheter is inserted bilaterally into the renal arteries and a specified amount of a neurolytic agent is inserted into the vessel walls.
Sponsors
Ablative Solutions, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Adult subject, age 18-80, male or female; 2. Subject has a target treatment vasculature diameter of ≥4 mm and ≤ 7 mm and length of ≥5 mm; 3. Subject has 3 measurements with a mean of office Systolic Blood Pressure of ≥150 mmHg AND office Diastolic Blood Pressure of ≥85 mmHg; 4. Subject has a 24-hour mean systolic Ambulatory Blood Pressure Measurement (ABPM) ≥135 mm Hg with ≥70% valid readings (as determined by measurement device); 5. Subject with hypertension is receiving and adhering to a stable medication regimen of at least 3 anti-hypertensive medications of different classes (for at least 4 consecutive weeks), one of which must be a diuretic; 6. Subject agrees to have all study procedures performed, to comply with medication regimen and is able and willing to comply with all study follow-up visits; 7. Subject has provided written informed consent.
Exclusion criteria
1. Subject has a contraindication known for conventional percutaneous interventional procedures such as: * intolerance for antiplatelet/anticoagulant therapy * known allergy to contrast media * bleeding disorders (such as bleeding diathesis, thrombocytopenia and severe anemia) 2. Subject has documented severe untreated obstructive sleep apnea (Apnea Hypopnea Index \[AHI\] ≥30 per hour); 3. Subjects with nephrotic syndrome; 4. Subjects on immunosuppressive medications or immunosuppressive doses of steroids; 5. Subject has type 1 diabetes mellitus; 6. Subject is pregnant or nursing or planning to become pregnant; 7. Subject has an eGFR ≤20 mL/min/1.73m2 , based on the CKD-EPI equation; 8. Subject has imaging-assessed renal artery anatomy abnormalities or variations based on Investigator's evaluation of the screening images \[i.e. MRA/CTA examination and/or renal angiography\]) meeting one of the following criteria: * Renal artery stenosis \>60% of the normal diameter segment (diameter stenosis, compared to the angiographically normal proximal or distal segment); * Any renal artery abnormality or disease that, per the physician assessment, precludes the safe insertion of the guiding catheter (such as but not limited to severe renal artery aneurysm, excessive tortuosity, severe renal artery calcification); * 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; 9. Subject has a history of nephrectomy, a single kidney or kidney tumor, or urinary tract obstruction (with potential for hydronephrosis); 10. Subject 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); 11. Subject has a renal transplant; 12. Subject has a history of myocardial infarction, unstable angina pectoris, or stroke/TIA within the last six months from planned procedure; 13. Subject has hemodynamically significant valvular heart disease; 14. Subject has heart failure (NYHA III or IV) or has an ejection fraction ≤30%; 15. Subject with chronic atrial fibrillation; 16. Subjects who are allergic or intolerant of the neurolytic agent (such as dehydrated alcohol); 17. Any contraindication to the imaging as required per the protocol; 18. Subject has a life expectancy of \<12 months; 19. Subject is currently enrolled in other potentially confounding research, i.e., another therapeutic or interventional research trial. Subjects enrolled in observational registries may still be eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With the Absence of Particular Events as Adjudicated by the CEC Through 1-month Post Procedure: | 1-month | The primary safety endpoint is defined by the absence of any of the following events as adjudicated by the CEC through 1-month post procedure: 1. Peri-procedural major vascular complications; 2. Major Bleeding as defined by the TIMI Bleeding Classification; 3. Acute Kidney Injury (AKI) within 1 month of the procedure 4. Peri-procedural death (within 1 month of the procedure) |
| Change in 24-hour Mean Ambulatory Systolic Blood Pressure From Baseline to 6 Months | 6 months | The primary performance endpoint is defined as a reduction of 24-hour mean ambulatory systolic blood pressure following treatment at 6 months, as compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With New Renal Arterial Stenosis > 60% | 6 months | Number of Participants with New renal arterial stenosis \> 60% from the baseline at the 6-month follow-up, to be confirmed by the same imaging method used at baseline. |
| Number of Subjects With Stroke or Transient Ischemic Attack (TIA) With 1 Month of the Procedure | 1 month | Stroke or TIA within 1 month of the procedure |
| Number of Subjects With Myocardial Infarction (MI) Within 1 Month of the Procedure | 1 month | Myocardial Infarction (MI) within 1 month of the procedure |
| Number of Participants With Major Adverse Events (MAE) Through 6 Months Post-Procedure | 6 months | Number of Participants with Major Adverse Events (MAE) through 6-month post-procedure. MAE is defined as the occurrence of any of the following: 1. All-cause death 2. End stage renal failure 3. Significant embolic event resulting in end-organ damage or requiring intervention to prevent it 4. Major Vascular Complications (including major artery dissections) 5. Significant new renal artery stenosis (\>60% diameter stenosis) 6. Hypertensive crisis (hypertensive emergency only) 7. Severe hypotension/syncope |
| Changes in Antihypertensive Medications at 7 Days, and 1, 3, 6 and 12 Months Post-Procedure | 7-day, 1, 3, 6 and 12 months | Changes in antihypertensive medications at 7-day, 1, 3, 6 and 12 months post procedure; |
| Changes in Systolic and Diastolic Clinic/Office Blood Pressure | 7-day, 1, 3, 6 and 12 months | Changes in systolic and diastolic clinic/office blood pressure following treatment compared to baseline, assessed at 7-day, 1, 3, 6 and 12 months post-procedure. |
| Changes in Systolic and Diastolic 24-hour Mean Daytime and Nighttime Ambulatory Blood Pressure | 1, 3, 6 and 12-months | Changes in systolic and diastolic 24-hour mean daytime and nighttime ambulatory blood pressure, assessed at 1, 3, 6 and 12-month post-procedure. |
| Numbr of Subjects With a Decline in eGFR by >25% From Baseline to 6 Months | 6 months | Proportion of subjects with a decline in eGFR by \>25% from baseline to 6-month follow-up; |
| Changes in Systolic 24-hour Mean Ambulatory Blood Pressure | 1, 3 and 12 months | Changes in systolic 24-hour mean ambulatory blood pressure assessed at 1, 3 and 12 months postprocedure; |
| Change in eGFR | 1, 3, 6 and 12 months | Change in eGFR from baseline, to evaluate the progression of Chronic Kidney Disease (CKD) after 1, 3, 6 and 12 months; |
| The Progression of Kidney Disease | 1, 3, 6, and 12 months | The progression of kidney disease in subjects with ≤60 mL/min/1.73m2 will be evaluated by comparing the change in eGFR during the study to the historical loss (reduction) of eGFR during the 3 years prior to renal denervation for each individual subject; |
| Change in Albuminuria | 3, 6, and 12 months | Change in albuminuria from baseline to 3 months post-procedure, with additional assessments at each study time point; |
| Change in Albuminuria Categorization | 3, 6, and 12 months | Change in albuminuria categorization from baseline to 3 months post-procedure, with additional assessments at each study time point; |
| Change in Serum Creatinine and Cystatin-C | 3, 6, and 12 months | Change in serum creatinine and cystatin-C from baseline to 3 months postprocedure, with additional assessments at each study time point. |
| Changes in Diastolic 24-hour Mean Ambulatory Blood Pressure | 1, 3, 6 and 12-months | Changes in systolic and diastolic 24-hour mean ambulatory blood pressure assessed at 1, 3, 6 and 12-month post-procedure. |
| Change in Serum Creatinine From Baseline to 6 Months | 6 months | Change in serum creatinine from baseline to 6-month follow-up |
Countries
Belgium, Czechia, Germany, Poland
Participant flow
Recruitment details
Withdrawal of consent (N=3)
Participants by arm
| Arm | Count |
|---|---|
| Renal Denervation by Neurolysis Infusion of 0.6 ml of dehydrated alcohol (not less than 95% by volume) 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.
Peregrine System Infusion Catheter: The Peregrine Catheter is inserted bilaterally into the renal arteries and a specified amount of a neurolytic agent is inserted into the vessel walls. | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Renal Denervation by Neurolysis | — |
|---|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 10 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Europe | 45 Participants | — |
| Sex: Female, Male Female | 17 Participants | — |
| Sex: Female, Male Male | 28 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 45 |
| other Total, other adverse events | 42 / 45 |
| serious Total, serious adverse events | 11 / 45 |
Outcome results
Primary
Change in 24-hour Mean Ambulatory Systolic Blood Pressure From Baseline to 6 Months
The primary performance endpoint is defined as a reduction of 24-hour mean ambulatory systolic blood pressure following treatment at 6 months, as compared to baseline.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Denervation by Neurolysis | Change in 24-hour Mean Ambulatory Systolic Blood Pressure From Baseline to 6 Months | -11 mmHg | Standard Deviation 14 |
Primary
Number of Subjects With the Absence of Particular Events as Adjudicated by the CEC Through 1-month Post Procedure:
The primary safety endpoint is defined by the absence of any of the following events as adjudicated by the CEC through 1-month post procedure: 1. Peri-procedural major vascular complications; 2. Major Bleeding as defined by the TIMI Bleeding Classification; 3. Acute Kidney Injury (AKI) within 1 month of the procedure 4. Peri-procedural death (within 1 month of the procedure)
Time frame: 1-month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Denervation by Neurolysis | Number of Subjects With the Absence of Particular Events as Adjudicated by the CEC Through 1-month Post Procedure: | 43 participants |
Secondary
Change in Albuminuria
Change in albuminuria from baseline to 3 months post-procedure, with additional assessments at each study time point;
Time frame: 3, 6, and 12 months
Secondary
Change in Albuminuria Categorization
Change in albuminuria categorization from baseline to 3 months post-procedure, with additional assessments at each study time point;
Time frame: 3, 6, and 12 months
Secondary
Change in eGFR
Change in eGFR from baseline, to evaluate the progression of Chronic Kidney Disease (CKD) after 1, 3, 6 and 12 months;
Time frame: 1, 3, 6 and 12 months
Secondary
Change in Serum Creatinine and Cystatin-C
Change in serum creatinine and cystatin-C from baseline to 3 months postprocedure, with additional assessments at each study time point.
Time frame: 3, 6, and 12 months
Secondary
Change in Serum Creatinine From Baseline to 6 Months
Change in serum creatinine from baseline to 6-month follow-up
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Denervation by Neurolysis | Change in Serum Creatinine From Baseline to 6 Months | 0.01 mg/dL | Standard Deviation 0.13 |
Secondary
Changes in Antihypertensive Medications at 7 Days, and 1, 3, 6 and 12 Months Post-Procedure
Changes in antihypertensive medications at 7-day, 1, 3, 6 and 12 months post procedure;
Time frame: 7-day, 1, 3, 6 and 12 months
Secondary
Changes in Diastolic 24-hour Mean Ambulatory Blood Pressure
Changes in systolic and diastolic 24-hour mean ambulatory blood pressure assessed at 1, 3, 6 and 12-month post-procedure.
Time frame: 1, 3, 6 and 12-months
Secondary
Changes in Systolic 24-hour Mean Ambulatory Blood Pressure
Changes in systolic 24-hour mean ambulatory blood pressure assessed at 1, 3 and 12 months postprocedure;
Time frame: 1, 3 and 12 months
Secondary
Changes in Systolic and Diastolic 24-hour Mean Daytime and Nighttime Ambulatory Blood Pressure
Changes in systolic and diastolic 24-hour mean daytime and nighttime ambulatory blood pressure, assessed at 1, 3, 6 and 12-month post-procedure.
Time frame: 1, 3, 6 and 12-months
Secondary
Changes in Systolic and Diastolic Clinic/Office Blood Pressure
Changes in systolic and diastolic clinic/office blood pressure following treatment compared to baseline, assessed at 7-day, 1, 3, 6 and 12 months post-procedure.
Time frame: 7-day, 1, 3, 6 and 12 months
Secondary
Number of Participants With Major Adverse Events (MAE) Through 6 Months Post-Procedure
Number of Participants with Major Adverse Events (MAE) through 6-month post-procedure. MAE is defined as the occurrence of any of the following: 1. All-cause death 2. End stage renal failure 3. Significant embolic event resulting in end-organ damage or requiring intervention to prevent it 4. Major Vascular Complications (including major artery dissections) 5. Significant new renal artery stenosis (\>60% diameter stenosis) 6. Hypertensive crisis (hypertensive emergency only) 7. Severe hypotension/syncope
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation by Neurolysis | Number of Participants With Major Adverse Events (MAE) Through 6 Months Post-Procedure | 3 Participants |
Secondary
Number of Participants With New Renal Arterial Stenosis > 60%
Number of Participants with New renal arterial stenosis \> 60% from the baseline at the 6-month follow-up, to be confirmed by the same imaging method used at baseline.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation by Neurolysis | Number of Participants With New Renal Arterial Stenosis > 60% | 0 Participants |
Secondary
Number of Subjects With Myocardial Infarction (MI) Within 1 Month of the Procedure
Myocardial Infarction (MI) within 1 month of the procedure
Time frame: 1 month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation by Neurolysis | Number of Subjects With Myocardial Infarction (MI) Within 1 Month of the Procedure | 0 Participants |
Secondary
Number of Subjects With Stroke or Transient Ischemic Attack (TIA) With 1 Month of the Procedure
Stroke or TIA within 1 month of the procedure
Time frame: 1 month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation by Neurolysis | Number of Subjects With Stroke or Transient Ischemic Attack (TIA) With 1 Month of the Procedure | 0 Participants |
Secondary
Numbr of Subjects With a Decline in eGFR by >25% From Baseline to 6 Months
Proportion of subjects with a decline in eGFR by \>25% from baseline to 6-month follow-up;
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation by Neurolysis | Numbr of Subjects With a Decline in eGFR by >25% From Baseline to 6 Months | 2 Participants |
Secondary
The Progression of Kidney Disease
The progression of kidney disease in subjects with ≤60 mL/min/1.73m2 will be evaluated by comparing the change in eGFR during the study to the historical loss (reduction) of eGFR during the 3 years prior to renal denervation for each individual subject;
Time frame: 1, 3, 6, and 12 months