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

NCT01208714 | Unknown Phase 4 DMC

• 1 other identifier: GPR-METRAS
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. 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. 2.Medical therapy: the drug regimen that had been optimized during the run-in period.

Conditions

Renal Artery Stenosis

Keywords

Renal artery stenosis; Atherosclerosis; Arterial hypertension; Percutaneous renal angioplasty; Stenting

Outcome Measures

Primary Outcomes (1)

• Glomerular filtration rate in the ischemic kidney after revascularization by means of percutaneous renal angioplasty (PTRAS) or optimal medical treatment.

  The Primary Objective of the study is 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 99TcDTPA sequential renal scintiscan

  24 months

Secondary Outcomes (3)

• Lowering blood pressure after revascularization by means of percutaneous renal angioplasty (PTRAS) or optimal medical treatment.

  1, 3, 6, 12, 24, 36, 48 and 60 months

• Preserving overall renal function after revascularization by means of percutaneous renal angioplasty (PTRAS) or optimal medical treatment.

  1, 3, 6, 12, 24, 36, 48 and 60 months

• Regression of damage in the target organs of hypertension, including cardiac hypertrophy, microalbuminuria and aortic stiffness after revascularization by means of percutaneous renal angioplasty (PTRAS) or optimal medical treatment.

  1, 3, 6, 12, 24, 36, 48 and 60 months

Study Arms (2)

revascularization

ACTIVE COMPARATOR

The patients randomized to this treatment will undergo PTA with stenting of the renal artery.

Procedure: revascularization

medical therapy

ACTIVE COMPARATOR

The patients randomized to this treatment will undergo optimal medical therapy

Drug: Optimal medical therapy

Interventions

Optimal medical therapy DRUG

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%).

medical therapy

revascularization PROCEDURE

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.

Also known as: Device: Palmaz Genesis stent on Cordis AMIIA delivery system

revascularization

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• RAS affecting the main renal artery or its major branches at angio-CT either \> 70% or, if \< 70 with post-stenotic dilatation AND
• resistance index (RI) \< 0.55 or \> 0.55 but \< 0.80 with evidence of intrarenal heterogeneity of the RI as revealed by a CV \> 10% in the RI across the upper, mid and lower third of each kidney.

You may not qualify if:

• refusal to participate to study,
• previous endovascular or surgical treatment of RAS,
• fibromuscular RAS,
• planned or actual pregnancy, or childbearing potential without measures adequate to prevent pregnancy,
• life expectancy \< 2 years,
• patient currently participating in another trial possibly influencing the safety of the patient and/or the outcomes of the study,
• co-morbid conditions limiting participation and follow-up.

Sponsors & Collaborators

• University Hospital Padova: lead

Study Sites (1)

Dept. Clinical and Experimental Medicine, University of Padova, Italy

Padua, 35128, Italy

Location

Related Publications (10)

• 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.

  PMID: 16148190 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.

  PMID: 17179020 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.

  PMID: 9495267 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.

  PMID: 14736007 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.

  PMID: 19907042 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.

  PMID: 20095015 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.

  PMID: 10658939 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.

  PMID: 18697874 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.

  PMID: 17470708 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.

  PMID: 11172177 BACKGROUND

MeSH Terms

Conditions

Renal Artery Obstruction; Atherosclerosis; Hypertension

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis

Study Officials

• Gian Paolo Rossi, MD, FACC

  Dept Clinical and Experimental Medicine (DMCS), University Hospital of Padova, Italy

  STUDY DIRECTOR

Central Study Contacts

Gian Paolo Rossi, MD, FAHA

CONTACT

0039 049 8213; gianpaolo.rossi@unipd.it

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 23, 2010
• First Posted: September 24, 2010
• Study Start: December 1, 2010
• Primary Completion: December 1, 2015
• Study Completion: March 1, 2016
• Last Updated: November 4, 2010

Record last verified: 2010-09

Locations

IT (1)