Medical and Endovascular Treatment of Atherosclerotic Renal Artery Stenosis (METRAS Study)

Summary

Renal atherosclerotic stenosis (RAS) is a prevalent cause of secondary hypertension (HT). Since there are still uncertainties as to whether and in what patients revascularization by means of percutaneous renal angioplasty (PTRAS) should be pursued, we designed a study exploiting an optimized patient selection strategy and using hard experimental endpoints to unravel these uncertainties.

Primary objective: to determine if revascularization by means of PTRAS is superior or equivalent to optimal medical treatment for preserving glomerular filtration rate in the ischemic kidney as assessed by 99mTcDTPA sequential renal scintiscan.

Secondary objectives: to determine if the two treatments are equivalent in lowering blood pressure (BP), preserving overall renal function and regressing damage in the target organs of hypertension.

Design: prospective multicenter randomized, unblinded two-arm study.

Eligible patients will have clinical and/or radiological evidence of unilateral or bilateral RAS, defined by stenosis of the proximal portion of the renal artery and its main bifurcations at angioCT. Duplex scan will exclude nephroangiosclerosis as the latter could bias the assessment of the outcome of revascularization.

Inclusion criteria. RAS affecting the main renal artery or its major branches at angio-CT either \> 70% or, if \< 70 with post-stenotic dilatation.

Renal function will be assessed with 99mTc-DTPA renal scintigraphy.

Sample size (30 patients per arm) was calculated to have a 90% power to detect a difference in means of GFR in the vascularized (or control untreated kidney) of 7.5 ml/min.

Arms

1. Revascularization: digital scan angiography and PTA with stenting of the renal artery at the ostium or at truncular level, plus optimal medical therapy.
2. Medical therapy: the drug regimen that had been optimized during the run-in period.

Experimental endpoints:

The absolute value of GFR assessed by 99TcDTPA in the ischemic kidney will be used as quantitative variable and compared between groups at each time point. A categorical definition of kidney loss, defined as a GFR in the ischemic kidney of \< 5 ml/min, will be also used and the rate of achievement of such endpoint will be compared.

Duration: 5 years.

Conditions

• Renal Artery Stenosis

Interventions

DRUG

Optimal medical therapy

Optimal medical therapy, including optimal antihypertensive therapy as defined by ESH/ESC Guidelines Mancia G. J Hypertens 2007; 25: 1105), antiplatelet and, if necessary, hypolipemic and hypoglycemic treatment. All patients will receive antiplatelet treatment with the same dose of aspirin (100 mg o.d.) or ticlopidine (250 mg b.i.d) if intolerant ASA, or clopidogrel (75 mg o.d.), if intolerant to ASA and ticlopidine, throughout the study period. LDL-cholesterol will be lowered to below 100 mg/dl, homocysteine if elevated will be lowered and treatment for diabetes will be optimized (HbA1c \< 6.5%).

PROCEDURE

revascularization

The patients randomized to this treatment will undergo digital scan angiography (DSA) and PTA with stenting of the renal artery. PTA will be performed at the ostium or at truncular level. Stenoses involving more distal arterial vessels will be recorded and considered for data analysis but will not be treated. The patients randomized to revascularization will continue on their antihypertensive drug regimen. The dose and number of drugs will be down-titrated with the aim of pursuing the target BP values.

Sponsors & Collaborators

• University Hospital Padova

  lead OTHER

Principal Investigators

• Gian Paolo Rossi, MD, FACC · Dept Clinical and Experimental Medicine (DMCS), University Hospital of Padova, Italy

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-12-31

Primary Completion

2015-12-31

Completion

2016-03-31

Countries

• Italy

Study Locations