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

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Recruiting
    • Aarhus University Hospital
    • Contact: Sebastian Nielsen, MD; Email: sebane@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: Steen Bonnema, MD, DMSc; Email: steen.bonnema@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.	Procedure: Renal artery stenting; Optimal medical therapy and percutaneous transluminal renal angioplasty with stent placement.
Sham Comparator: Sham treatment; Sham treatment.	Procedure: Sham treatment; Optimal medical therapy and sham treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in 24-hour ambulatory systolic blood pressure.	Changes in 24-hour ambulatory systolic blood pressure from baseline to 6 months after renal artery stenting compared with optimal medical treatment alone in patients with 24-hour ambulatory average systolic blood pressure ≥150 mmHg at baseline.	6 months after PTRA/sham

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in kidney function.	Changes in kidney function (estimated glomerular filtration rate) from baseline to 6 months after renal artery stenting compared with optimal medical treatment alone.	6 months after PTRA/sham
Changes in antihypertensive treatment (defined daily doses).	Changes in antihypertensive treatment (defined daily doses) from baseline to 6 months after renal artery stenting compared with optimal medical treatment alone.	6 months after PTRA/sham
Changes in 24-hour ambulatory systolic blood pressure (statistically adjusted for treatment changes).	Changes in 24-hour ambulatory systolic blood pressure from baseline to 6 months after renal artery stenting compared with optimal medical treatment alone in patients with 24-hour ambulatory average systolic blood pressure ≥150 mmHg at baseline. Changes in systolic blood pressure will be adjusted for changes in the defined daily doses (DDD) of antihypertensive medications, where a change of 1DDD equals a change of 5 mmHg in the systolic blood pressure.	6 months after PTRA/sham
Number of participants with cardiovascular and kidney outcomes.	Clinical events included in the composite end point from baseline to 6-month follow-up: 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 Clinical events are defined using the same criteria as in the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study except for progressive renal insufficiency (in the CORAL study defined as a reduction from baseline of 30% or more in the estimated GFR). Only the first event per participant is included in the composite.	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 optimal medical treatment alone.	6 months after PTRA/sham
Health status on 12-Item Short Form Survey (SF-12).	Changes in 12-item short form health survey (SF-12) from baseline to 6 months after renal artery stenting compared with optimal medical treatment alone. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning.	6 months after PTRA/sham
Number of participants with procedure-related major adverse events (MAE) <30 days of PTRA/sham.	Number of participants with procedure-related MAEs including: all cause mortality; rupture, dissection, perforation or occlusion of renal artery; critical bleeding (need of blood transfusion); embolization; significant loss of kidney function (reduction from baseline of 50% or more in eGFR); permanent renal-replacement therapy; ipsilateral nephrectomy; access complications requiring treatment: bleeding, pseudoaneurysm or thrombosis; stent thrombosis after renal artery stenting	<30 days after PTRA/sham

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Odense University Hospital; Aarhus University Hospital; Rigshospitalet, Denmark; The Novo Nordic Foundation; 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. Erratum In: J Am Heart Assoc. 2023 Apr 18;12(8):e020845.

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): May 9, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Hypertension, Renal; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hypertension; Constriction, Pathologic; Renal Artery Obstruction; Hypertension, Renovascular
• 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