Renal Denervation in ADPKD- RDN-ADPKD Study

NCT ID: NCT05460169

Last Updated: 2024-11-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-14
• Study Completion Date: 2028-03-31

Brief Summary

RDN-ADPKD is a prospective, randomized (1:1, central randomization), single-center, hypothesis-generating, feasibility study. The purpose of the RDN-ADPKD study is to demonstrate efficacy and document safety of renal denervation (RDN) with the Paradise System in hypertensive patients with ADPKD.

Detailed Description

1. Introduction:Increased blood pressure (BP) is a common finding in patients with autosomal dominant polycystic kidney disease (ADPKD) which is one of the leading causes of end stage renal disease. Previously, it was shown that hypertensive patients with ADPKD have increased sympathetic nerve activity regardless of renal function. This was one of the pathogenetic mechanisms that leads to the progression of renal failure, even independent of BP. Recent clinical studies have indicated that invasive, catheter-based renal denervation (RDN) decreases sympathetic nerve activity. Up to date, only two single case reports have suggested a safe and effective procedure of RDN in an ADPKD patient with uncontrolled hypertension.

2. Study purpose: The purpose of the RDN-ADPKD pilot study is to demonstrate efficacy and document safety of RDN with the Paradise System in hypertensive patients with ADPKD.

3. Study design: RDN-ADPKD is a prospective, randomized (1:1, central randomization), single-center, hypothesis-generating, feasibility study.

Patients are randomized into (immediate) I-RDN-group and (delayed) D-RDN-group, respectively. After 3 months, patients in the D-RDN-group will undergo RDN-procedure and will be followed for additional 36 months. Hence, study design allows several comparisons both of whole study group (at same time-point of follow-up) as well as between I-RDN-group and D-RDN-group.

4. Patient population: 44 hypertensive patients with ADPKD are randomized with 22 patients allocated to the I-RDN-group and 22 patients to the D-RDN-group (receiving RDN after 3 months), respectively.

5. Primary endpoint: The primary endpoint of this pilot study is the change in systolic 24-h ambulatory BP at 3 months post-procedure in the whole study group (irrespective whether treated immediate [I-RDN-group] or delayed [D-RDN-group]) compared to baseline.

6. Visit and Follow-Up Schedule: The primary objective will be assessed at 13 weeks (3 months) post-procedure in both groups. Scheduled in-clinic follow-up (FU) visits will occur at least at 13 (3 months) and 26 (6 months) 52 (12 months), 78 weeks (18 months),104 weeks (24 months), 130 weeks (30 months) and 156 weeks (36 months) post procedure; however, scheduled Follow-Up visits at 3, 7,20 weeks, 78 weeks and 130 weeks post-procedure are possible as in-clinic FU visit as well as ambulant visit at the allocation centre(s) of the referring physician.

7. Randomization: The subjects will be randomized to I-RDN group or D-RDN group at Visit 2.

8. Medication Adherence: Adherence to drug therapy will be captured by interviewing patients, checking the patient's BP diary and by urinary toxicological analysis at baseline, 26 weeks, 52 weeks, 104 weeks and 156 weeks post-procedure visit.

9. Safety Signals: A major combined safety endpoint is the incidence of any major adverse events (MAE) through the 36 months Follow-up.

10. Escape Criteria: Enrolled subjects will be excluded:

• if home BP increases to ≥160 systolic or ≥100 mmHg diastolic pre-randomization, confirmed by office (attended) BP ≥170/105 mmHg will be excluded
• if office (attended) BP exceeds ≥170/105 mmHg pre-randomization, confirmed by 7-day average of home BP measurements ≥ 160/100 mmHg (excluding white coat effect) or confirmed by office (attended) BP ≥170/105 mmHg at another study visit.

11. Ethics: The study will be conducted in accordance with the declaration of Helsinki, REGULATION (EU) 2017/745, EN ISO 14155:2020, FDA 21 CFR parts 50, 54, 56, 812 and other applicable local and national regulations.

Conditions

Uncontrolled Hypertension; Autosomal Dominant Polycystic Kidney Disease; Renal Denervation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Immediate Renal Denervation Group (I-RDN-group)

Patients are randomized into (immediate) I-RDN-group and (delayed) D-RDN-group, respectively. All subjects in the I-RDN-group will undergo a diagnostic, renal angiogram immediately (based on clinical grounds to rule out renal artery stenosis), which should be per Institutional practice via femoral artery access. Renal Denervation procedure will be applied using the Paradise® Renal Denervation System. The Paradise® Renal Denervation System is a catheter-based device designed to use ultrasound energy to thermally ablate the afferent and efferent nerves surrounding the renal artery and serving the kidney.

Group Type: ACTIVE_COMPARATOR

Renal denervation

Intervention Type: DEVICE

The Paradise® Renal Denervation System (Paradise System) is CE-marked in countries accepting the CE mark. The system is a catheter-based device designed to use ultrasound energy to thermally ablate the afferent and efferent nerves surrounding the renal artery and serving the kidney.

Delayed Renal Denervation Group (D-RDN-group)

3 months after randomization, patients in the (delayed) D-RDN-group will undergo renal denervation procedure after undergoing a diagnostic, renal angiogram and will be followed for additional 36 months.

Group Type: OTHER

Renal denervation

Intervention Type: DEVICE

The Paradise® Renal Denervation System (Paradise System) is CE-marked in countries accepting the CE mark. The system is a catheter-based device designed to use ultrasound energy to thermally ablate the afferent and efferent nerves surrounding the renal artery and serving the kidney.

Interventions

Renal denervation

The Paradise® Renal Denervation System (Paradise System) is CE-marked in countries accepting the CE mark. The system is a catheter-based device designed to use ultrasound energy to thermally ablate the afferent and efferent nerves surrounding the renal artery and serving the kidney.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Patients with ADPKD
• Patient is adhering to a stable drug regimen without changes for a minimum of 4 weeks
• Individual is ≥ 18 years of age, both genders are included

Exclusion Criteria

• eGFR < 40ml/min/1.73m² (according to the currently used estimation formulas: MDRD (Modification of Diet in Renal Disease), CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration))
• Anatomically significant renal artery abnormality in either renal artery which in the eyes of the interventionalist would interfere with safe catheter placement
• Prior renal denervation procedure
• Office (attended) BP ≥180 mmHg systolic and/or ≥110 mmHg diastolic
• 24-h ambulatory BP ≥160 mmHg systolic
• Other cause of hypertension that can be treated by intervention/surgery (e.g. hemodynamically relevant renal artery stenosis, functional adrenal adenoma)
• Type 1 diabetes mellitus
• Proteinuria (>3g/g Kreatinin)
• Contraindication to MRI
• Individual has experienced a myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within 3 months of the screening visit
• Subject is pregnant, nursing, or intends to become pregnant
• Enrollment in another interventional research protocol
• Any condition that, at the discretion of the investigator, would preclude participation in the study (e.g. non-adherence)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Hospital FAU Erlangen-Nürnberg

Erlangen, , Germany

Countries

Germany

References

St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

Reference Type: DERIVED

PMID: 39356039 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RDN2021ADPKD

Identifier Type: -

Identifier Source: org_study_id