Effects of Percutaneous Transluminal Renal Angioplasty of Atherosclerotic Renal Artery Stenosis in High-Risk Patients. (DAN-PTRAII)

Effects of Percutaneous Transluminal Renal Angioplasty of Atherosclerotic Renal Artery Stenosis in High-Risk Patients - a Danish Nationwide Randomized Sham-Controlled Study.

The goal of this clinical trial is to document a beneficial effect of percutaneous transluminal renal angioplasty (PTRA) of atherosclerotic renal artery stenosis in high-risk patients selected according to the criteria used in the DAN-PTRA study. The main questions the trial aims to answer are if renal artery stenting compared with optimal medical treatment alone has beneficial effects on:

• Blood pressure
• Kidney function
• Hospitalizations for heart failure

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Percutaneous Transluminal Angioplasty; Renovascular Hypertension; Renal Artery Stenosis Atherosclerotic; Renovascular Hypertension With Renal Failure
• Intervention / Treatment: Drug: Optimal medical therapy (OMT); Diagnostic test: Catheter-based angiography; Diagnostic test: Measurement of translesional pressure gradients; Procedure: Renal artery stenting; Procedure: Sham (No Treatment)

Detailed Description

Even with optimal medical care, patients with renovascular disease have a very high risk of cardiovascular events and an expected poor outcome. One treatment option of atherosclerotic renal artery stenosis is percutaneous transluminal renal angioplasty with stent placement. Renal artery stenting is, however, still a subject of debate as randomized trials have failed to show a benefit of this compared with optimal medical treatment alone. Following the results of the large CORAL trial in 2014, we established the national prospective DAN-PTRA study using strict and well-defined criteria to select patients for renal artery stenting. In this study, we observed a reduction in blood pressure, an improved kidney function, and a decrease in new hospital admissions due to heart failure after renal artery stenting.

The DAN-PTRAII study is a nationwide high-quality randomized, sham-controlled clinical trial in patients with severe renovascular disease due to atherosclerotic renal artery stenosis. Only patients who fulfill the inclusion criteria on optimal medical treatment can enter the study and only the operator and his team will know whether the patients receive renal artery stenting or sham treatment. Participants will be followed closely for 6 months after the treatment to evaluate the effects of renal artery stenting compared with optimal medical treatment alone on blood pressure, kidney function and hospitalizations due to heart failure.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mark Reinhard, MD, PhD; Phone Number: +45 40460321; Email: m.reinhard@dadlnet.dk
• Study Contact Backup: Name: Sebastian Nielsen, MD; Phone Number: +45 23100484; Email: sebane@rm.dk

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Recruiting
    • Aarhus University Hospital
    • Contact: Sebastian Nielsen, MD; Email: sebane@rm.dk
    • Contact: Mark Reinhard, MD, PhD; Email: markrein@rm.dk
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
    • Contact: Jonas P Eiberg, MD, PhD; Email: jonas.peter.eiberg@regionh.dk
  • Odense C, Denmark, 5000
    • Recruiting
    • Odense University Hospital
    • Contact: Michael D Schultz, MD; Email: michael.dyrehauge.schultz@rsyd.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. One or more severe atherosclerotic renal artery stenoses defined as a stenosis ≥70% by catheter-based angiography.

2. In addition, at least one of the following high-risk clinical syndromes:

   1. Resistant hypertension with average 24-hour ambulatory systolic blood pressure ≥150 mmHg despite ≥3 antihypertensive drugs including a diuretic, if tolerated, and each prescribed at optimal doses.
   2. Rapidly declining kidney function with a reduction in estimated GFR of >5 mL/min per 1.73m2 per year and average 24-hour ambulatory systolic blood pressure ≥140 mmHg despite ≥3 antihypertensive drugs including a diuretic, if tolerated, and each prescribed at optimal doses.
   3. Hospital admissions with acute decompensated heart failure (≥2 hospitalizations for heart failure or ≥1 hospitalizations for sudden, "flash" pulmonary edema) with no obvious explanations such as nonadherence, left ventricular ejection fraction <40%, or valvular heart disease and average 24-hour ambulatory systolic blood pressure ≥140 mmHg despite ≥3 antihypertensive drugs including a diuretic, if tolerated, and each prescribed at optimal doses.

All 24-hour ambulatory blood pressure monitorings are performed after nurse-administered medication.

Exclusion Criteria:

• Unable to provide informed consent.
• Treatment-resistant heart failure episodes presumed caused by renovascular disease.
• Rapidly declining kidney function/acute kidney failure approaching the need for dialysis presumed caused by renovascular disease.
• Fibromuscular dysplasia or other non-atherosclerotic renal artery stenosis known to be present prior to randomization.
• Pregnancy or unknown pregnancy status in female of childbearing potential.
• Kidney size <7 cm (pole to pole length) supplied by target vessel.
• Previous kidney transplant.
• Previous PTRA treatment.
• Presence of a renal artery stenosis not amenable for treatment with a stent.

Patients who are not eligible for randomization but treated with renal artery stenting outside the protocol are followed according to the DAN-PTRAII protocol in order to account for all PTRA treatments performed in Denmark in the study period.

Patients treated with renal artery stenting without randomization in the study period include patients with:

1. Treatment-resistant heart failure episodes presumed caused by renovascular disease.
2. Rapidly declining kidney function/acute kidney failure approaching the need for dialysis presumed caused by renovascular disease.

3. At least one of the listed high-risk clinical syndromes AND one or more significant atherosclerotic renal artery stenoses defined as a stenosis of 50-69% by catheter-based angiography with:

   • a mean translesional gradient of ≥10 mm Hg, or
   • a systolic translesional gradient of ≥20 mm Hg, or
   • a renal fractional flow reserve (Pd/Pa) of ≤0.8

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Renal artery stenting; Percutaneous transluminal renal angioplasty with stent placement	Drug: Optimal medical therapy (OMT); Optimal medical therapy, including maximally tolerated renin-angiotensin system blockade with either an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker.; Diagnostic test: Catheter-based angiography; Catheter-based angiography performed in accordance with the study protocol.; Diagnostic test: Measurement of translesional pressure gradients; Measurement of translesional pressure gradients performed in accordance with the study protocol.; Procedure: Renal artery stenting; Renal artery stenting performed in accordance with the study protocol.
Sham Comparator: Sham procedure	Drug: Optimal medical therapy (OMT); Optimal medical therapy, including maximally tolerated renin-angiotensin system blockade with either an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker.; Diagnostic test: Catheter-based angiography; Catheter-based angiography performed in accordance with the study protocol.; Diagnostic test: Measurement of translesional pressure gradients; Measurement of translesional pressure gradients performed in accordance with the study protocol.; Procedure: Sham (No Treatment); Sham procedure performed in accordance with the study protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 24-hour ambulatory systolic blood pressure	Defined as the between-group difference in the change in 24-hour ambulatory systolic blood pressure from baseline to 6 months.	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in estimated glomerular filtration rate (eGFR)	Defined as the between-group difference in the change in estimated glomerular filtration rate (eGFR) from baseline to 6 months.	Baseline, Day 1, Day 7, Day 21, 6 weeks, 3 months, 4.5 months, and 6 months
Change in attended automated office systolic blood pressure	Defined as the between-group difference in the change in attended automated office systolic blood pressure from baseline to 6 months.	Baseline, 3 months, and 6 months
Change in unattended automated office systolic blood pressure	Defined as the between-group difference in the change in unattended automated office systolic blood pressure from baseline to 6 months.	Baseline, 3 months, and 6 months
Change in defined daily dose (DDD) of antihypertensive medications	Defined as the between-group difference in the change in defined daily dose (DDD) of antihypertensive medications from baseline to 6 months.	Baseline, 3 months, and 6 months
Change in the number of antihypertensive medications	Defined as the between-group difference in the change in the number of antihypertensive medications from baseline to 6 months.	Baseline, 3 months, and 6 months
Change in 24-hour ambulatory systolic blood pressure (statistically adjusted for treatment changes)	Defined as the between-group difference in the change in 24-hour ambulatory systolic blood pressure from baseline to 6 months, adjusted for changes in antihypertensive medication burden (1 DDD = 5 mmHg).	Baseline, 3 months, and 6 months
Number of participants with cardiovascular or kidney outcomes	Clinical events from baseline to 6 months after renal artery stenting, compared with clinical events in the sham control group. Clinical events are defined using the same criteria as in the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, except for progressive renal insufficiency (defined in CORAL as a reduction from baseline of 30% or more in estimated GFR). Clinical events included in the composite endpoint from baseline to 6-month follow-up are: Death from cardiovascular causes; Death from renal causes; Stroke; Myocardial infarction; Hospitalization for congestive heart failure; Progressive renal insufficiency (a reduction from baseline of 50% or more in estimated GFR); Permanent renal-replacement therapy Only the first event per participant is included in the composite.	From baseline to 6 months after PTRA/sham
Number of deaths from any cause	Death from any cause from baseline to 6 months after renal artery stenting, compared with death from any cause in the sham control group.	From baseline to 6 months after PTRA/sham
Change in health status on 12-item Short Form Health Survey (SF-12)	Defined as the between-group difference in the change in 12-item Short Form Health Survey (SF-12) scores from baseline to 6 months. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning.	Baseline, 3 months, and 6 months
Number of serious adverse events (SAEs), procedure-related adverse events (≤24 hours), and postoperative adverse events (>24 hours) occurring within 30 days after the procedure	All SAEs, procedure-related adverse events (≤24 hours), and postoperative adverse events (>24 hours) occurring within 30 days after the procedure will be systematically recorded. Events include, but are not limited to: Death from any cause; Rupture, dissection, occlusion, or perforation of the renal artery; Stent thrombosis of the PTRA-treated renal artery; Embolic complications affecting the kidney or peripheral circulation (upper or lower extremity depending on access site); Bleeding requiring transfusion; Embolization or nephrectomy due to bleeding or other complications; Access-related complications requiring treatment: bleeding, thrombosis, or pseudoaneurysm; Need for acute dialysis; Clinical events as defined above	From baseline to 30 days after PTRA/sham
Evaluation of Diagnostic Techniques	As part of the study, the applicability of diagnostic techniques that remain insufficiently described in the context of renal artery stenosis will be evaluated separately according to the protocol. The following examinations will be assessed: (a) Doppler ultrasound, (b) echocardiography, (c) renography, (d) invasive pressure measurements across stenoses, (e) computational fluid dynamics (CFD) simulations, and (f) proteomics analysis.	From baseline to 6 months after PTRA/sham

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Odense University Hospital; Aarhus University Hospital; Rigshospitalet, Denmark; The Novo Nordic Foundation; Aalborg University Hospital; Holbaek Sygehus; Gødstrup Hospital; The Augustinus Foundation, Denmark.; Amsterdam UMC
• Investigators: Principal Investigator: Mark Reinhard, MD, PhD, Aarhus University Hospital

Publications and helpful links

General Publications

• Reinhard M, Schousboe K, Andersen UB, Buus NH, Rantanen JM, Bech JN, Mafi HM, Langfeldt S, Bharadwaz A, Horlyck A, Jensen MK, Jeppesen J, Olsen MH, Jacobsen IA, Bibby BM, Christensen KL. Renal Artery Stenting in Consecutive High-Risk Patients With Atherosclerotic Renovascular Disease: A Prospective 2-Center Cohort Study. J Am Heart Assoc. 2022 Apr 5;11(7):e024421. doi: 10.1161/JAHA.121.024421. Epub 2022 Mar 24.

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: April 3, 2023
• First Submitted That Met QC Criteria: April 17, 2023
• First Posted (Actual): April 28, 2023

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Heart Diseases; Hypertension; Hypertension, Renal; Heart Failure; Hypertension, Renovascular; salicylhydroxamic acid
• Other Study ID Numbers: DAN-PTRAII

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No