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.

Timeline

Start

2010-12

Primary completion

2015-12

Completion

2016-03

Publications

• Background Cheung CM, Hegarty J, Kalra PA. Dilemmas in the management of renal artery stenosis. Br Med Bull. 2005 Sep 7;73-74:35-55. doi: 10.1093/bmb/ldh049. Print 2005.
• Background Guo H, Kalra PA, Gilbertson DT, Liu J, Chen SC, Collins AJ, Foley RN. Atherosclerotic renovascular disease in older US patients starting dialysis, 1996 to 2001. Circulation. 2007 Jan 2;115(1):50-8. doi: 10.1161/CIRCULATIONAHA.106.637751. Epub 2006 Dec 18.
• Background Plouin PF, Chatellier G, Darne B, Raynaud A. Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis: a randomized trial. Essai Multicentrique Medicaments vs Angioplastie (EMMA) Study Group. Hypertension. 1998 Mar;31(3):823-9. doi: 10.1161/01.hyp.31.3.823.
• Background Bax L, Mali WP, Buskens E, Koomans HA, Beutler JJ, Braam B, Beek FJ, Rabelink TJ, Postma CT, Huysmans FT, Deinum J, Thien T, Schultze Kool LJ, Woittiez AJ, Kouwenberg JJ, van den Meiracker AH, Pattynama PM, van de Ven PJ, Vroegindeweij D, Doorenbos CJ, Aarts JC, Kroon AA, de Leeuw PW, de Haan MW, van Engelshoven JM, Rutten MJ, van Montfrans GA, Reekers JA, Plouin PF, La Batide Alanore A, Azizi M, Raynaud A, Harden PN, Cowling M; STAR Study Group. The benefit of STent placement and blood pressure and lipid-lowering for the prevention of progression of renal dysfunction caused by Atherosclerotic ostial stenosis of the Renal artery. The STAR-study: rationale and study design. J Nephrol. 2003 Nov-Dec;16(6):807-12.
• Background ASTRAL Investigators; Wheatley K, Ives N, Gray R, Kalra PA, Moss JG, Baigent C, Carr S, Chalmers N, Eadington D, Hamilton G, Lipkin G, Nicholson A, Scoble J. Revascularization versus medical therapy for renal-artery stenosis. N Engl J Med. 2009 Nov 12;361(20):1953-62. doi: 10.1056/NEJMoa0905368.
• Background White CJ. Kiss my astral: one seriously flawed study of renal stenting after another. Catheter Cardiovasc Interv. 2010 Feb 1;75(2):305-7. doi: 10.1002/ccd.22416. No abstract available.
• Background van Jaarsveld BC, Pieterman H, van Dijk LC, van Seijen AJ, Krijnen P, Derkx FH, Man in't Veld AJ, Schalekamp MA. Inter-observer variability in the angiographic assessment of renal artery stenosis. DRASTIC study group. Dutch Renal Artery Stenosis Intervention Cooperative. J Hypertens. 1999 Dec;17(12 Pt 1):1731-6. doi: 10.1097/00004872-199917120-00010.
• Background Maiolino G, Cesari M, Sticchi D, Zanchetta M, Pedon L, Antezza K, Pessina AC, Rossi GP. Plasma adiponectin for prediction of cardiovascular events and mortality in high-risk patients. J Clin Endocrinol Metab. 2008 Sep;93(9):3333-40. doi: 10.1210/jc.2007-2405. Epub 2008 Aug 12.
• Background D'Agostino RB Jr. Propensity scores in cardiovascular research. Circulation. 2007 May 1;115(17):2340-3. doi: 10.1161/CIRCULATIONAHA.105.594952. No abstract available.
• Background Radermacher J, Chavan A, Bleck J, Vitzthum A, Stoess B, Gebel MJ, Galanski M, Koch KM, Haller H. Use of Doppler ultrasonography to predict the outcome of therapy for renal-artery stenosis. N Engl J Med. 2001 Feb 8;344(6):410-7. doi: 10.1056/NEJM200102083440603.

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