E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020772 |
E.1.2 | Term | Hypertension |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of renal denervation by alcohol-mediated neurolysis using the Peregrine Kit in hypertensive subjects, when used in the absence of antihypertensive medications, as evaluated by change in mean 24-hour ambulatory systolic blood pressure (SBP) from baseline to 8 weeks post-treatment. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the acute and chronic safety of renal denervation by alcohol-mediated neurolysis using the Peregrine Kit in hypertensive subjects, up to 2 years post-treatment. • To evaluate the efficacy of renal denervation by alcohol-mediated neurolysis using the Peregrine Kit on blood pressure in hypertensive subjects, up to 1 year post-treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Prior to run-in period: 1. Subject has provided written informed consent. 2. Male or female subject, aged ≥18 and ≤80 years at time of enrollment. 3. If subject has a documented history of uncontrolled hypertension (see definition in Definition of Terms section of protocol) and is currently taking no (0) antihypertensive medications, he/she must: • Have 3 office blood pressure measurements with a mean office systolic blood pressure (SBP) of ≥140 mmHg and ≤180 mmHg AND mean office diastolic blood pressure (DBP) ≥90 mmHg, and • Be willing to adhere to the no-medication regimen for at least 12 weeks (4-week run-in period and 8-week post-treatment period). 4. If subject has a documented history of uncontrolled hypertension (see definition in Definition of Terms section of protocol) and is currently taking 1 or 2 antihypertensive medications, he/she must: • Have 3 office blood pressure measurements with a mean office SBP of ≥120 mmHg and ≤180 mmHg and • Be willing to discontinue his/her antihypertensive medication(s), and to adhere to the no-medication regimen for at least 12 weeks (4-week run-in period and 8-week post-treatment period). 5. Investigator judges that the subject can be discontinued safely from all current antihypertensive medication (where applicable) and managed safely for at least 12 weeks (4-week run-in period and 8-week post-treatment period) without antihypertensive medication intake. 6. 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. 7. 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: 8. Subject has 3 office blood pressure measurements with a mean office SBP of ≥140 mmHg and ≤180 mmHg AND mean office DBP ≥90 mmHg. 9. Subject has a mean 24-hour ambulatory SBP of ≥135 mmHg and ≤170 mmHg with ≥70% valid readings (as determined by ABPM measurement device). |
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E.4 | Principal 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 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 2. Subject has an acute or sub-acute infection that the Investigator judges would pose unacceptable risks to the subject 3. 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) 4. Subject has documented severe untreated obstructive sleep apnea (AHI ≥30 per hour) 5. 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 6. Subject has a history of pre-eclampsia 7. Subject has orthostatic hypotension at screening, or documented history of orthostatic hypotension within 12 months prior to the planned procedure, defined as a drop in blood pressure that is >20mmHg in SBP and/or >10mmHg in DBP within 3 minutes upon standing from sitting or from a lying down face-up (supine) position 8. Subject has Type 1 diabetes mellitus, or uncontrolled Type 2 diabetes mellitus (defined as hemoglobin A1c [HbA1c] ≥9.0%) 9. Subject has an eGFR of ≤45 mL/min/1.73 m2, based on the CKD-EPI equation; or is on chronic renal replacement therapy 10. Subject has nephrotic syndrome 11. Subject has a history of recurrent (>1 episode) kidney stones, or history of kidney stones within 12 months prior to the planned procedure 12. Subject has a history of nephrectomy, a single kidney or kidney tumor, or urinary tract obstruction (with potential for hydronephrosis). 13. Subject has a renal transplant, or is known to have a non-functioning kidney or unequal renal size (>2cm difference in renal length between kidneys associated with a chronic kidney disease or a deterioration of the kidney function) 14. Subject has a history of myocardial infarction, unstable angina pectoris, or stroke/TIA within 6 months prior to the planned procedure 15. Subject has any of the following conditions: severe cardiac valvestenosis, heart failure (NYHA Class III or IV), chronic atrial fibrillation, and known primary pulmonary hypertension (>60mmHg PA or RV systolic pressure) 16. Subject is allergic or intolerant to the neurolytic agent (dehydrated alcohol) 17. Subject 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 18. Any contraindication to the imaging as required per the protocol 19. Subject for whom an ABPM device cannot be used due to arm size (>42cm arm circumference) or other reasons 20. 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 21. Subject has a known history of drug use or alcohol dependency, 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 22. If female, subject is pregnant or lactating at the time of enrollment or planning to become pregnant during the trial time period. 23. Subject 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. 24. Subject is in custody or an institution. 25. Subject has close affiliation with the study site or sponsor (e.g. employee, close relative of an employee). 26. Subject has a history of hypertensive emergency in the previous 3 months (see definition of hypertensive emergencies in Definition of Terms section of protocol). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in mean 24-hour ambulatory SBP |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
from baseline to 8 weeks post-treatment |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints: 1. Change in mean 24-hour, daytime (07:00 to 21:59), and nighttime (22:00 to 06:59) ambulatory SBP and DBP 2. Change in mean office SBP and DBP 3. Percentage of subjects controlled to target blood pressure values 4. Use of antihypertensive medication(s) (emergency use medication) 5. Use of antihypertensive medication(s) (including increases/decreases, titrated according to standardized formula to maintain a target SBP of <140 mmHg and ≥90 mmHg) 6. Compliance with not taking antihypertensive medications
Secondary safety endpoints: 1. Major adverse events (MAEs), as adjudicated by the Clinical Events Committee (CEC) 2. Changes in eGFR 3. Decreases in eGFR >25% 4. Rate of adverse events (serious and non-serious), peri-procedurally 5. Device success (defined as the ability to insert the Peregrine Catheter into the lumen of the renal artery [target vessel], deploy the guide tubes inside the renal artery, deploy the needles through the arterial wall, deliver the intended dose of alcohol, retract the needles and the guide tubes back in the catheter, and remove the catheter from the access site without any related complications or events) 6. Procedure success (defined as device success with freedom from peri-procedural MAEs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary efficacy endpoints: 1 & 2. from baseline to time points post-treatment 3 & 6. throughout the study 4. from time of procedure to 8 weeks post-treatment 5. from 8 week to 6 months and 1 year post-treatment 6. through 8 weeks post-treatment
Secondary safety endpoints: 1 & 6. through 30 days post-treatment 2 & 3. from baseline to 8 weeks, 6 month and 1 year post-treatment 4. at discharge and at each of the follow-up time points 5. at the time of the procedure |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Sham-procedure (only renal angiography performed) |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
Belgium |
France |
Germany |
Ireland |
United Kingdom |
Netherlands |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the date of final database lock for the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |