This study has been transitioned to CTIS with ID 2024-512525-83-00 check the CTIS register for the current data. Primary Objective (Randomized Controlled Trial [RCT] Cohort): to evaluate the efficacy of renal denervation by alcohol-mediated…
ID
Source
Brief title
Condition
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint is defined as the change in mean 24-hour
ambulatory (SBP) from baseline to 3 months post-procedure.
Secondary outcome
Secondary efficacy endpoints:
1. Change in mean office SBP from baseline to 3 months post-procedure.
2. Change in mean office SBP from baseline to 4 weeks post-procedure.
3. Change in mean 24-hour ambulatory SBP from baseline to 6 months
post-procedure.
4. Change in mean office SBP from baseline to 6 months post-procedure.
5. Changes (decreases or increases) in antihypertensive medication regimen from
procedure to 6 months post-procedure (titrated according to standardized
formula to maintain a target office SBP of <140 mmHg and >=90 mmHg).
6. Change in mean daytime (07:00 to 21:59) ambulatory SBP from baseline to 3
months post-procedure.
7. Change in mean daytime ambulatory SBP from baseline to 6 months
post-procedure.
8. Change in mean office DBP from baseline to 3 months and then 6 months
post-procedure.
9. Change in mean 24-hour ambulatory DBP from baseline to 3 months and then 6
months post-procedure.
10. Change in mean daytime ambulatory DBP from baseline to 3 months and then 6
months post-procedure.
11. Changes (decreases or increases) in antihypertensive medication regimen
from 3 months to 6 months post-procedure (titrated according to standardized
formula to maintain a target office SBP of <140 mmHg and >=90 mmHg).
12. Change in mean nighttime (22:00 to 06:59) ambulatory SBP from baseline to 3
months and then 6 months post-procedure.
13. Change in mean nighttime ambulatory DBP from baseline to 3 months and then
6 months post-procedure.
14. ABPM Responders, defined as the proportion of subjects with a drop of >=5
mmHg in 24-hour ambulatory SBP at 3 months compared with baseline.
15. Office BP Responders, defined as the proportion of subjects with a drop of
>=10 mmHg in office SBP at 3 months compared with baseline.
16. Reduction of both office SBP and DBP to normal (<140/90 mmHg) at 3, 6 and
12 months as compared to baseline.
17. Changes (any decrease or increase) in antihypertensive medication regimen
from procedure to 3 months post-procedure.
Secondary safety endpoints:
• Major adverse events (MAEs) through 30 days post-procedure, as adjudicated by
the Clinical Events Committee (CEC). An MAE is defined as any of the following:
o All-cause death
o Myocardial infarction
o End-stage renal disease (ESRD) (eGFR <15 mL/min/1.73 m2 or need for renal
replacement therapy)
o Significant embolic event resulting in end-organ damage or requiring
intervention
o Major vascular complications, including major renal artery dissection
(including main and accessory arteries), renal artery aneurysm or
pseudoaneurysm that required intervention or led to renal artery stenosis (>60%
diameter stenosis)
o Major bleeding related to renal denervation within the renal arteries, or
related to the Peregrine Catheters when in the body (per bleeding definition in
the protocol)
o Significant acute (post-procedural) renal artery stenosis (>60% diameter
stenosis) as indicated by the renal angiogram post renal denervation, and
confirmed by the angiography core laboratory, which led to one of the
following: (i) acute kidney injury per modified Risk, Injury, Failure, Loss of
kidney function, and End-stage kidney disease (RIFLE) definition, as confirmed
by renal function blood test, or (ii) percutaneous intervention.
o Hypertensive crisis (hypertensive emergency only)
o Hypotensive crisis
o Symptomatic hypotension that required a change in antihypertensive
medications, or medications to increase blood pressure (e.g. persistent
syncope, lightheadedness)
• MAEs at 3, 6, and 12 months and 2 and 3 years.
• Renal artery stenosis >60% diameter as indicated by imaging at 6 months.
• Changes in eGFR from baseline to 3 months and 6 months post-procedure.
• Decreases in eGFR >25% from baseline to 3 months and 6 months post-procedure.
• Rate of adverse events (serious and non-serious), peri-procedurally, at
discharge, and at each of the follow-up time points.
• 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).
• Procedure success (defined as device success with freedom from
peri-procedural MAEs).
Background summary
To obtain an assessment of the efficacy and safety of renal denervation by
alcohol-mediated neurolysis using the Peregrine System Kits (also referred to
as Peregrine Kits) in uncontrolled hypertensive subjects when used in
combination with antihypertensive medications.
Study objective
This study has been transitioned to CTIS with ID 2024-512525-83-00 check the CTIS register for the current data.
Primary Objective (Randomized Controlled Trial [RCT] Cohort): to evaluate the
efficacy of renal denervation by alcohol-mediated neurolysis using the
Peregrine Kits in uncontrolled hypertensive subjects when used in combination
with antihypertensive medications.
Secondary Objectives
• To evaluate the acute and chronic safety of renal denervation by
alcohol-mediated neurolysis using the Peregrine Kits in uncontrolled
hypertensive subjects when used in combination with antihypertensive
medications.
• To evaluate the sustained efficacy of renal denervation by alcohol-mediated
neurolysis using the Peregrine Kits in uncontrolled hypertensive subjects when
used in combination with antihypertensive medications.
• To evaluate the performance of the Peregrine Kits (co-packaged combination of
the alcohol and the Peregrine Systems) for its intended use.
Study design
The study comprises 2 sequential cohorts:
RCT Cohort:
This is a Phase 3, prospective, randomized, blinded, sham procedure-controlled,
multicenter trial to assess the efficacy and safety of renal denervation by
alcohol-mediated neurolysis using the Peregrine Kit. Subjects with uncontrolled
hypertension, who are taking 2, 3, 4, or 5 antihypertensive medications at
enrollment will be recruited. Following screening, eligible subjects will enter
a 4-week run-in period during which they will remain on a stable regimen of
antihypertensive medications (i.e. no changes) before the procedure.
Subjects who continue to be eligible at the end of the run-in period will
attend the study site for the day of procedure. All subjects will receive
sedation and analgesia and undergo a diagnostic renal angiogram per standard
procedures. Subjects will be randomized in a 1:1 ratio to 1 of the following 2
groups via central randomization (stratified by study site):
- Treatment Arm: renal denervation (using the Peregrine Kit) performed with
alcohol (0.6 mL per treated renal artery) infused through the
Peregrine Catheter (minimum treatment: the 2 main renal arteries [1 per side];
physician is also permitted to treat up to 1 additional accessory artery on
each side. Thus, the planned maximum total dose is 4 x 0.6 mL = 2.4 mL)
- Sham Control Arm: only diagnostic renal angiography performed. No renal
denervation and no alcohol infusion will be performed.
After 3 months, changes in antihypertensive medications are permitted according
to the protocol-defined criteria and proposed titration scheme.
Follow-up visits will be performed at 4 weeks, 8 weeks, 3 months, 4 months, 5
months, 6 months, 1 year, 2 years, and 3 years.
The RCT Cohort will be unblinded after the last subject has reached the 6-month
visit.
Safety Cohort:
The Safety Cohort will be initiated following unblinding of the RCT Cohort when
the last subject has reached the 6-month follow-up and only if the primary
efficacy endpoint of the RCT Cohort is met. This will be an open-label study to
assess the safety of renal denervation by alcohol-mediated neurolysis using the
Peregrine Kit. All subjects will undergo renal denervation using the Peregrine
Kit. The investigational product and entry criteria are the same as for the RCT
Cohort.
Subjects will enter the Safety Cohort either (i) from the Sham Control Arm in
the RCT Cohort* or (ii) as new subjects.
Follow-up visits in the Safety Cohort will be performed at 30 days, 8 weeks, 3
months, 6 months, and 1 year.
Intervention
In this protocol, *treatment* is a general term that refers to the renal
denervation procedure (i.e. Treatment Arm) or control renal angiography (i.e.
Sham Control Arm).
Each subject will be randomized to either the Treatment Arm or Sham Control Arm
whilst part of the RCT Cohort.
Subjects who are in the Sham Control Arm may be offered the possibility to
undergo renal denervation in a crossover phase
Treatment Arm:
The test product in this study is a co-packaged combination product, the
Peregrine Kits, which includes the Peregrine Systems and alcohol for injection.
The catheter will be used to deliver a dose of 0.6 mL alcohol by direct
infusion to the perivascular space of each renal artery in a single treatment
session (i.e. a target dose of 1.2 mL). The 2 main renal arteries (1 on each
side) will be treated. However, the treating physician is permitted to treat up
to 1 additional accessory renal artery on each side (during the same treatment
session) as well (depending on individual subject anatomy). Thus, the planned
maximum total dose per subject is 4 x 0.6 mL = 2.4 mL.
Sham Control Arm:
The sham control in this study is renal angiography only. There will be no
insertion of the Peregrine Systems and no alcohol infusion (i.e. no renal
denervation).
For subjects who are in the sham control arm, the amount of contrast used
during the renal angiography will not exceed 100 mL.
Study burden and risks
The burden and risks of the subjects are different in both arms. Subjects in
the procedure arm will have more- and higher burden and risks based on the fact
that they will have a renal denervation while the subject in the control arm
will not have the denervation, but will have to undergo a renal angiography.
But the investigator and sponsors of the study are providing mitigation for
every potential risk, and after assessing the risks vs. the benefits, have
concluded that the potential benefits outweigh the known and potential risks
associated with the participation in this study. ( see protocol page 46 - 49).
Potential Risks
Subjects in this study will be exposed to potential risks and burden as follows:
1. The exposure to risks related to the percutaneous procedure and the use of a
novel catheter and the infusion of a drug in a location that has not been
previously approved.
2. Exposure to risks associated with renal angiography (injection of contrast
without receiving treatment)
3. The exposure to radiation and contrast and any risks associated with
sedation while not receiving the treatment
4. The burden of having a blood pressure monitor and a cuff around the arm for
24-hours, with blood pressure measurements taken every 30 minutes.
Potential Benefits
1. Subjects will be on a very close medical monitoring to ensure their safety.
2. If the renal denervation is ultimately proven to be effective, the patients
who are taking 2, 3, 4, or 5 antihypertensive medications will have fewer risks
associated with the administration of medications and their side effects or
intolerance. In addition, there will be no concerns of non-compliance with
taking the medications.
3. Although subjects in the sham group will not receive the potential benefit
of the renal denervation, they will benefit from close medical monitoring and
tests by their treating physicians to ensure their safety. These subjects will
also be offered to receive the same treatment if they choose to, after the Data
Safety Monitoring Board (DSMB) has reviewed the 6-month data from all subjects,
the study has been unblinded, and the subject has completed the 1-year
follow-up visit.
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US
Listed location countries
Age
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. 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.
4. 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
5. 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
6. Female subjects of childbearing potential must agree to use acceptable
methods of contraception, 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 maintained the same antihypertensive medication regimen for at
least 4 weeks (28 days) prior to the procedure
9. 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
1. Subject has documented severe untreated obstructive sleep apnea
2. 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
3. Subject has a history of pre-eclampsia within the 5 years prior to study
entry.
4. Subject has orthostatic hypotension at baseline, or documented history of
orthostatic hypotension within 12 months prior to the planned procedure
5. Any contraindication to the imaging as required per the protocol.
6. 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 <3 mm 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
7. Subject has a renal transplant, or is known to have a non-functioning kidney
or unequal renal size
8. Subject has a history of nephrectomy, a single kidney or kidney tumor, or
urinary tract obstruction
9. Subject has a history of recurrent kidney stones, or history of kidney
stones within 12 months prior to the planned procedure
10. Subject has an eGFR of <=45 mL/min/1.73 m2, based on the CKD-EPI equation;
or is on chronic renal replacement therapy
11. Subject has nephrotic syndrome
12. Subject for whom an ABPM device cannot be used due to arm size or other
reasons as identified by the investigator
13. Subject has any of the following conditions: severe cardiac valve stenosis,
heart failure (NYHA Class III or IV), atrial fibrillation (defined as at least
one documented episode in the 12 months before study entry), and known primary
pulmonary hypertension (>60 mmHg pulmonary artery or right ventricular systolic
pressure).
14. Subject has an acute or sub-acute infection that the investigator judges
would pose unacceptable procedural risks to the subject
15. Subject has Type 1 diabetes mellitus, or uncontrolled Type 2 diabetes
mellitus
16. 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, occlusive peripheral vascular
disease that would preclude percutaneous femoral access for the procedure
17. Subject has a known hypersensitivity to the neurolytic agent
18. 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
19. Subject is being treated chronically (e.g. daily use) with NSAIDs,
immunosuppressive medications, or immunosuppressive doses of steroids
20. Subject has a history of myocardial infarction, unstable angina pectoris,
or stroke/transient ischemic attack (TIA) within 6 months prior to the planned
procedure.
21. If female, subject is pregnant or lactating at the time of enrollment or
planning to become pregnant during the trial time period.
22. 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.
23. 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
24. Subject is in custody or in an institution
25. 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).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-512525-83-00 |
| EudraCT | EUCTR2016-002545-32-NL |
| ClinicalTrials.gov | NCT02910414 |
| CCMO | NL67011.056.19 |