Effects of Percutaneous Transluminal Renal Angioplasty of Atherosclerotic Renal Artery Stenosis in High-Risk Patients.

Official title

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

Overview

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

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.

Interventions

• 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.
• Procedure Sham (No Treatment)
  Sham procedure performed in accordance with the study protocol.

Primary outcome measures

• Change in 24-hour ambulatory systolic blood pressure [Time frame: Baseline and 6 months]

Secondary outcome measures (11)

• Change in estimated glomerular filtration rate (eGFR) [Time frame: 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 [Time frame: Baseline, 3 months, and 6 months]
• Change in unattended automated office systolic blood pressure [Time frame: Baseline, 3 months, and 6 months]
• Change in defined daily dose (DDD) of antihypertensive medications [Time frame: Baseline, 3 months, and 6 months]
• Change in the number of antihypertensive medications [Time frame: Baseline, 3 months, and 6 months]
• Change in 24-hour ambulatory systolic blood pressure (statistically adjusted for treatment changes) [Time frame: Baseline, 3 months, and 6 months]
• Number of participants with cardiovascular or kidney outcomes [Time frame: From baseline to 6 months after PTRA/sham]
• Number of deaths from any cause [Time frame: From baseline to 6 months after PTRA/sham]
• Change in health status on 12-item Short Form Health Survey (SF-12) [Time frame: 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 [Time frame: From baseline to 30 days after PTRA/sham]
• Evaluation of Diagnostic Techniques [Time frame: From baseline to 6 months after PTRA/sham]

Eligibility criteria

Inclusion criteria

• One or more severe atherosclerotic renal artery stenoses defined as a stenosis ≥70% by catheter-based angiography.
• In addition, at least one of the following high-risk clinical syndromes:

• 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.
• 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.
• 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:

• 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.
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Denmark · 3 centers

• Aarhus University Hospital — Aarhus N
• Rigshospitalet — Copenhagen
• Odense University Hospital — Odense C

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. Epu PMID 35322677

Identifiers

NCT: NCT05834803 · DAN-PTRAII

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗