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

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.

Study Overview

• Status: Unknown
• Conditions: Atherosclerosis; Chronic Kidney Disease; Hypertension, Renovascular; Renal Artery Stenosis; Ischemic Nephropathy
• Intervention / Treatment: Procedure: PTRS; Device: renal artery stent; Device: renal artery stent; Drug: Medical treatment

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Piacenza, Italy, 29100
    • Divisione di Nefrologia e Dialisi, "Guglielmo da Saliceto" Hospital, Azienda USL Piacenza

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: B:PTRS; B: the same medical therapy, as previously described in group A, associated with PTRS	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
ACTIVE_COMPARATOR: A:medical therapy; hypotensive drugs, statins and antiplatelet therapy	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; Drug: Medical treatment; hypotensive drugs, statins and anti-platelets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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)	0.5, 1 and 2 years follow up plus extended 4 yrs

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Azienda Unità Sanitaria Locale di Piacenza
• Investigators: Principal Investigator: Roberto Scarpioni, Divisione Nefrologia e Dialisi, "Guglielmo da Saliceto" Hospital, Azienda USL Piacenza, Italy; Principal Investigator: Emanuele Michieletti, U.O. Radiologia II "Guglielmo da Saliceto" Hospital, Piacenza

Publications and helpful links

General Publications

• Scarpioni R, Michieletti E, Cristinelli L, Ugolotti U, Scolari F, Venturelli C, Cancarini G, Pecchini P, Malberti F, Maroldi R, Rozzi G, Olivetti L. Atherosclerotic renovascular disease: medical therapy versus medical therapy plus renal artery stenting in preventing renal failure progression: the rationale and study design of a prospective, multicenter and randomized trial (NITER). J Nephrol. 2005 Jul-Aug;18(4):423-8.

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (ANTICIPATED): September 1, 2008
• Study Completion (ANTICIPATED): May 1, 2009

Study Registration Dates

• First Submitted: December 1, 2009
• First Submitted That Met QC Criteria: December 1, 2009
• First Posted (ESTIMATE): December 2, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): December 2, 2009
• Last Update Submitted That Met QC Criteria: December 1, 2009
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: Hypertension; Angioplasty; Vascular diseases; Randomized controlled trials; High blood pressure; Renal insufficiency; kidney diseases; Atherosclerotic reno vascular disease (ARVD); Cardio- and cerebro- vascular comorbidity; End stage renal disease (ERSD); Ischemic nephropathy; Percutaneous transluminal renal artery stenting (PTRS); Renal artery stenosis (RAS)
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Urologic Diseases; Renal Insufficiency; Pathological Conditions, Anatomical; Hypertension, Renal; Hypertension; Kidney Diseases; Renal Insufficiency, Chronic; Ischemia; Constriction, Pathologic; Atherosclerosis; Renal Artery Obstruction; Hypertension, Renovascular
• Other Study ID Numbers: 388-2002