Renal Denervation in ADPKD- RDN-ADPKD Study
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
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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.
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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.
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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 6 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.
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Patient population: 40 hypertensive patients with ADPKD are randomized with 20 patients allocated to the I-RDN-group and 20 patients to the D-RDN-group (receiving RDN after 3 months), respectively.
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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.
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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) weeks post procedure; however, scheduled FU visits at 3 (V4, V8), 7 (V5, V9), and 20 weeks (V9, V11) post-procedure are possible as in-clinic FU visit as well as ambulant visit at the allocation centre(s) of the referring physician.
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Randomization: The subjects will be randomized to I-RDN group or D-RDN group at Visit 2.
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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, 13 and 26 weeks post-procedure visit.
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Safety Signals: A major combined safety endpoint is the incidence of any major adverse events (MAE) through the 6 month FU.
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Escape Criteria: Enrolled subjects will be excluded:
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if home BP increases to ≥160 systolic or ≥100 mmHg diastolic pre-randomization, confirmed by office (attended) BP ≥170/105 mmHg will be excluded
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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.
- 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 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. |
Device: 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.
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| Other: 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 6 months. |
Device: 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.
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Outcome Measures
Primary Outcome Measures
- change in systolic 24-h ambulatory BP [whole study group] [3 months post-procedure]
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
Secondary Outcome Measures
- Change in systolic 24-h ambulatory BP [separate study groups] [3 months post-procedure]
Change in systolic 24-h ambulatory BP at 3 months post-procedure from baseline in the I-RDN-group versus the change prior procedure from baseline in D-RDN-group
- Change in systolic 24-h ambulatory BP [separate study groups] [6 months post-procedure]
Change in systolic 24-h ambulatory BP at 6 months post-procedure from baseline in the I-RDN-group versus the change prior procedure from baseline in D-RDN-group
- Change in systolic 24-h ambulatory BP [whole study group] [6 months post-procedure]
Change in systolic 24-h ambulatory BP at 6 months post-procedure in the whole study group (irrespective whether treated immediate [I-RDN-group] or delayed [D-RDN-group]) compared to baseline
- Change in diastolic 24-h ambulatory BP [whole study group] [3 and 6 months post-procedure]
Change in diastolic 24-h ambulatory BP at 3 and 6 months post-procedure in the whole study group compared to baseline
- Change in diastolic 24-h ambulatory BP [separate study groups] [3 and 6 months post-procedure]
Change in diastolic 24-h ambulatory BP at 3 and 6 months post-procedure from baseline in the I-RDN-group versus the change prior procedure from baseline in D-RDN-group
- Change in systolic office (attended) BP [whole study group] [3 and 6 months post-procedure]
Change in systolic office (attended) BP at 3 and 6 months post-procedure in the whole study group compared to baseline
- Change in diastolic office (attended) BP [whole study group] [3 and 6 months post-procedure]
Change in diastolic office (attended) BP at 3 and 6 months post-procedure in the whole study group compared to baseline
- Change in systolic office (attended) BP [separate study groups] [3 and 6 months post-procedure]
Change in systolic office (attended) BP at 3 and 6 months post-procedure from baseline in the I-RDN-group versus the change prior procedure from baseline in D-RDN-group
- Change in diastolic office (attended) BP [separate study groups] [3 and 6 months post-procedure]
Change in diastolic office (attended) BP at 3 and 6 months post-procedure from baseline in the I-RDN-group versus the change prior procedure from baseline in D-RDN-group
- Change in serum creatinine derived estimated glomerular filtration rate (eGFR) [whole study group] [3 and 6 months post-procedure]
Change in serum creatinine derived estimated glomerular filtration rate (eGFR) at 3 and 6 months post-procedure in the whole study group compared to baseline
- Change in serum creatinine derived eGFR [separate study groups] [3 and 6 months post-procedure]
Change in serum creatinine derived eGFR at 3 and 6 months post-procedure from baseline in the I-RDN-group versus the change prior procedure from baseline in D-RDN-group
- Change in cystatin C derived eGFR [separate study groups] [3 and 6 months post-procedure]
Change in cystatin C derived eGFR at 3 and 6 months post-procedure from baseline in the I-RDN-group versus the change prior procedure from baseline in D-RDN-group
- Change in cystatin C derived eGFR at 3 and 6 months post-procedure [whole study group] [3 and 6 months post-procedure]
Change in cystatin C derived estimated glomerular filtration rate (eGFR) at 3 and 6 months post-procedure in the whole study group compared to baseline
- Change in plasma and urinary biomarkers (e.g. albumin, IgG, α1MG, β2MG, KIM-1, NGAL, MCP-1) [whole study group] [6 months post-procedure]
Change in plasma and urinary biomarkers (e.g. albumin, IgG, α1MG, β2MG, KIM-1, NGAL, MCP-1) at 6 months post-procedure in the whole study group compared to baseline
- Change in total kidney volume (assessed by magnetic resonance imaging) [whole study group] [6 months post-procedure]
Change in total kidney volume (assessed by magnetic resonance imaging) at 6 months post-procedure in the whole study group compared to baseline
- Change in measured GFR (assessed by single-shot iohexol clearance) [whole study group] [6 months post-procedure]
Change in measured GFR (assessed by single-shot iohexol clearance) at 6 months post-procedure in the whole study group compared to baseline
- Change in albuminuria quantitatively and by category [whole study group] [6 months post-procedure]
Change in albuminuria quantitatively and by category at 6 months post-procedure in the whole study group compared to baseline
- (Qualitatively) hematuria determined by urine dipstick [whole study group] [3 and 6 months post-procedure]
(Qualitatively) hematuria determined by urine dipstick at 3 and 6 months post-procedure in the whole study group compared to baseline
- Level of pain (related to autosomal dominant polycystic kidney disease) determined by the use of a visual analogue scale [whole study group] [3 and 6 months post-procedure]
Level of pain (related to autosomal dominant polycystic kidney disease) determined by the use of a visual analogue scale (minimum value=0, representing no pain; maximum value=100, representing most imaginable pain) at 3 and 6 months post-procedure in the whole study group compared to baseline.
- Change in Quality of life (QoL) (e.g. EQ-5D-5L) [whole study group] [3 and 6 months post-procedure]
Change in Quality of life (QoL) (e.g. EQ-5D-5L; minimum value=0, representing best imaginable health status; maximum value=100, representing worst imaginable health status) at 3 and 6 months post-procedure in the whole study group compared to baseline
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients with ADPKD
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Systolic office (attended) BP ≥130 mmHg or diastolic office (attended) BP ≥80 mmHg confirmed by 24-h ambulatory BP systolic ≥125 mmHg or diastolic ≥75 mmHg despite treatment with 1-4 drug classes (RAS blockade is mandatory, unless intolerance to RAS blockers has been documented) The rationale of these inclusion criteria reflect the November 2021 updated knowledge of RDN according to international consensus reports, in particular in face of conducting clinic studies and randomized controlled trials and does not necessarily reflect the current application of RDN in clinical practice). Moreover, the most recent updated KDIGO guidelines recommend a target office BP < 120 mmHg in patients with chronic kidney disease.1.
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Patient is adhering to a stable drug regimen without changes for a minimum of 4 weeks
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Individual is ≥ 18 years of age, both genders are included
Exclusion Criteria:
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eGFR < 45ml/min/1.73m² (according to the currently used estimation formulas: MDRD (Modification of Diet in Renal Disease), CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration))
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Anatomically significant renal artery abnormality in either renal artery which in the eyes of the interventionalist would interfere with safe catheter placement
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Prior renal denervation procedure
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Office (attended) BP ≥180 mmHg systolic and/or ≥110 mmHg diastolic
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24-h ambulatory BP ≥160 mmHg systolic
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Other cause of hypertension that can be treated by intervention/surgery (e.g. hemodynamically relevant renal artery stenosis, functional adrenal adenoma)
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Type 1 diabetes mellitus
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Proteinuria (>3g/g Kreatinin)
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Contraindication to MRI
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Individual has experienced a myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within 3 months of the screening visit
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Subject is pregnant, nursing, or intends to become pregnant
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Enrollment in another interventional research protocol
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Any condition that, at the discretion of the investigator, would preclude participation in the study (e.g. non-adherence)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital FAU Erlangen-Nürnberg | Erlangen | Germany | 91054 |
Sponsors and Collaborators
- University of Erlangen-Nürnberg Medical School
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RDN2021ADPKD