Revascularization of Renal Artery Stenosis Versus Medical Therapy for the Treatment of Ischemic Nephropathy

Official Title: “Phase 4 Study of Medical Therapy Versus Medical Therapy Plus Renal Artery Stenting in Preventing the Progression of Renal Failure in Atherosclerotic Renovascular Disease”

The aim of the study is to value, in patients with chronic kidney disease and hypertension, whether medical therapy plus interventional renal artery revascularization is superior to medical therapy alone for the treatment of hemodynamically significant (>70%) atherosclerotic renal artery stenosis, diagnosed by duplex doppler ultrasonography and confirmed by magnetic resonance angiography, in terms of avoidance of the progression of renal damage, control of hypertension and in reducing the cerebro and cardiovascular complications.

Atherosclerotic renovascular disease (ARVD), due to renal hypoperfusion caused by mono or bilateral renal artery stenosis (RAS), is a increasing cause of chronic kidney disease and many elderly patients start dialysis due to ARDVD. Moreover ARVD is frequently progressive and reduces life-expectancy more than other causes of end stage renal disease, with a mortality rate higher than in patients with stable angina, similar to that of patients operated for colon cancer.

Unfortunately, there is not a definite therapy to cure this disease, despite important advancements in both medical therapy and in interventional radiology. Aim of the study is to see whether percutaneous transluminal interventional radiology plus stenting (PTRS) of the renal artery offers more, in terms of both preventing the progression of renal failure and controlling the hypertension, compared with the medical therapy addressed to control hypertension, improve the dyslipidemic profile and optimise the platelet anti-aggregant therapy, following the most recent guidelines. The eligible patients will be centrally randomized to:

1. medical treatment with hypotensive drugs (all class of hypotensive agents will be used according to single-center experience including drugs agent on renin-angiotensin-aldosterone-system, when permitted), lipid lowering therapy (namely all class of statins-or hydroxymethylglutaryl-coA reductase inhibitors)and anti-platelet (acetylsalicylate and/or ticlopidine or clopidrogel according to single-center experience) or to

2. the same medical therapy, as previously described in group a, associated with PTRS, according to a standardized protocol, with a follow up at 2 years extended to other 2 years

Intervention(s) in this Clinical Trial

• Drug: Medical treatment
  • hypotensive drugs, statins and anti-platelets
• Procedure: PTRS
  • Percutaneous transluminal renal artery stenting. The same medical therapy, as in group A, plus PTRS
• Device: renal artery stent
  • Non-drug intervention, percutaneous transluminal renal artery stent angioplasty
• Device: renal artery stent
  • Adding the renal artery stenting (in group B) to the optimal medical therapy (as in group A) that includes hypotensive drugs, statins and antiplatelet therapy

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: B:PTRS
  • B: the same medical therapy, as previously described in group A, associated with PTRS
• Active Comparator: A:medical therapy
  • hypotensive drugs, statins and antiplatelet therapy

Primary Measures

• Death, Initiation of dialysis therapy or either serum creatinine increase more than 20% or reduction by > 20% in estimated clearance of creatinine (with MDRD formula)
  • Time Frame: 0.5, 1 and 2 years follow up plus extended 4 yrs
    Safety Issue?: Yes

Secondary Measures

• Systolic and diastolic blood pressure values at 0.5, 1 and 2 yrs follow up, with an extended follow up after 2 yrs
  • Time Frame: 0.5, 1 and 2 years follow up plus extended 4 yrs
    Safety Issue?: Yes
• Number of hypotensive drugs
  • Time Frame: 0.5, 1 and 2 years follow up plus extended 4 yrs
    Safety Issue?: Yes
• Results of renal scintigraphy
  • Time Frame: 0.5, 1 and 2 years follow up plus extended 4 yrs
    Safety Issue?: Yes
• Incidence of complications due to interventional manoeuvres
  • Time Frame: 0.5, 1 and 2 years follow up plus extended 4 yrs
    Safety Issue?: Yes
• Changes in the incidence of vascular complications in extra-renal districts
  • Time Frame: 0.5, 1 and 2 years follow up plus extended 4 yrs
    Safety Issue?: Yes

Inclusion Criteria:

• Age ≤ 80 years
• Presence of ostial renal artery stenosis ≥ 70% (determined by Duplex Doppler ultrasonography and confirmed by Magnetic Resonance valuated by at least two experienced operators)
• Serum creatinine ≤ 3 mg/dl and/or creatinine clearance (Modification of Diet in Renal
• Disease, MDRD formula)≥ 30 ml/min, defined as stage 3 or greater CKD based on
• National Kidney Foundation classification
• Longitudinal ultrasonographic diameter of the stenotic kidney ≥ 8 cm
• Blood pressure values ≤ 150/90 mmHg with the use of less than four hypotensives drugs

Exclusion Criteria:

• Age > 80 years
• Other well-known nephropathy cause of renal failure
• Duplex doppler ultrasonography Resistive Index values >0.8
• Total occlusion of renal artery lumen
• Occurrence of cerebral or cardiac vascular diseases in the 6 months before the enrolment in the study
• Malignancy with a life expectation less than one year
• Previous documented cholesterol thrombo embolization episodes (clinically, bioptically or instrumentally)
• Liver failure
• Cardiac failure (NYHA IV class) or instable angina
• Well-known intolerance or contraindications to the use of iodinated contrast media, to statins or to anti platelets drugs
• Previous renal angioplasty
• Pregnancy

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 45 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Azienda Unità Sanitaria Locale di Piacenza Other

Overall Clinical Trial Officials and Contacts

Roberto Scarpioni Principal Investigator Divisione Nefrologia e Dialisi, "Guglielmo da Saliceto" Hospital, Azienda USL Piacenza, Italy  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01023373

Study ID Number: 388-2002

ClinicalTrials.gov Identifier: NCT01023373

Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health