Clinical trial updates at Charing Cross

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The Global Endovascular Forum at the 27th Charing Cross International Symposium saw the latest updates being presented from trials including SIROCCO II, ASTRAL, MAVEric, SAPPHIRE and MIMIC.SIROCCO II

Two-year angiographic results from the SIROlimus Coated Cordis S.M.A.R.T. Nitinol Self-expandable Stent for the Treatment of Obstructive Superficial Femoral Artery Disease (SIROCCO II) study were presented at the Symposium. This was a double-blind, randomised prospective study (sirolimus vs. bare stent) in patients with obstructive superficial femoral artery disease (>70%). The primary endpoints were stent mean diameter via quantitative angiography determined within six months after stent placement.

SIROCCO II enrolled 57 patients with > 70% stenosis of >7 to <14.5cm or total occlusion >4 to <14.5cm with a maximum of two S.M.A.R.T. stents. A total of 29 patients received the Sirolimus stent, 28 patients received the bare metal stent. A total of 30 patients participated in the 24-months angiographic follow up, with 16 patients receiving the S.M.A.R.T. stent. Two investigational sites did not participate. Study Investigator, Dr Stephen Duda, reported that Stent Mean Diameter was 3.42mm in the S.M.A.R.T. group and 3.35 mm in the control (bare metal) group (P=0.941). In-stent restenosis was unreadable in three patients in the Sirolimus group (18.8%) and in two patients (14.3%) in the control group. Patent in-stent restenosis was 56.3% (nine patients) in the Sirolimus group and 57.1% (eight patients) in the control group. In stent restenosis >50 and <70% was present in four patients (25%) in the Sirolimus group and present in two patients (14.3%) in the control group. In stent restenosis >70 and <100% was present in one patient (7.1%) in the control group, however, none was located in the Sirolimus group. In addition, occlusion was present in one patient (7.1%) in the control group, none was located in the Sirolimus group. The combined SIROCCO Trials (93 patients) recorded a total of 15 stent fractures: eight (17.0%) in the Sirolimus group (n=47) and seven (15.2%) in the control group (n=46). Duda noted that stent fractures are less likely with overlap areas, but frequently adjacent to the overlaps and with single or fewer stent implantation after six months. Therefore, fractures are associated with multiple stents and longer stented lengths. All the fractures were asymptomatic with a single ulceration at site of type IV fracture, single restenosis near site of type I fracture and there was no relationship between fracture and restenosis. The 24 months SIROCCO studies results confirm that Sirolimus eluting S.M.A.R.T. stents are safe for superficial femoral artery treatment. ASTRAL

Jon Moss, Glasgow, UK, presented an update from the Angioplasty and STent for Renal Artery Lesions (ASTRAL) Trial, at the CX Symposium.

Endovascular stenting is being used with increasing frequency among patients with atherosclerotic renovascular disease (ARVD). Although stenting does result in obvious improvements in arterial patency, there is currently no good evidence that this is matched by an improvement in renal function.

The ASTRAL trial is designed to answer the question whether renal stenting plus best medical treatment is better than best medical treatment alone in preserving or improving renal function in patients with ARVD.

The primary outcome measure is renal function as assessed by reciprocal serum creatinine plots based on annual assessments. Secondary measures of efficacy include: blood pressure; urinary protein excretion; serious vascular events (such as myocardial infarction or stroke).

The trial is funded by the UK’s Medical Research Council and the National Kidney Research Fund together with an educational grant from Medtronic Inc.

The trial is powered to randomize 1,000 patients in a 1:1 fashion. There are just over 50 active centres mostly based in the UK but also in Australia and New Zealand.

To date, a total of 520 patients have been randomised making ASTRAL the largest renovascular trial ever, in fact larger than all the other trials put together. Recruitment will continue for a further 20 months and any centres interested in participating should contact j.moss@clinmed.gla.ac.uk, renal-trials@bham.ac.uk or visit www.astral.bham.ac.uk.MAVEric

Ron Fairman, Philadelphia, US, presented one year results of the Medtronic AVE Self-Expanding Carotid Stent System in the Treatment of Carotid Stenosis (MAVErIC) II results. The studies are a series of trials designed to demonstrate the safety and efficacy of Medtronic’s Exponent Self-Expanding Carotid Stent System with the GuardWire Temporary Occlusion and Aspiration System for the treatment of carotid stenosis in patients at high-risk for peri-procedural complications of carotid endartectomy.

Fairman said the MAVErIC I & II clinical studies demonstrated an acceptable overall combined major adverse event, target lesion revascularisation and target vessel revascularisation rate at 365-days with an major adverse event rate of 11.8% (59/498), target lesion revascularisation rate of 1.4% (7/498) and target vessel revascularization rate of 0.6% (3/498).

The MAVErIC I clinical trial was a 99-patient feasibility study designed to demonstrate the safety of the Exponent self-expanding carotid stent with the GuardWire balloon occlusion and aspiration system for the treatment of carotid stenosis. The study completed enrolment in December 2002 and was performed at 16 centers in the US.

In his presentation, Fairman said the MAVErIC I Feasibility trial results had an overall major adverse event rate of 6.1% (death – neurologic causes – 1%, MI 1%, ipsilateral stroke 4%), a target lesion revascularisation rate of 2% and a target vessel revascularisation rate of 1%.

The MAVErIC II clinical trial was a 399-patient pivotal trial at 34 sites, with an MA rate of 13.3% – death 9.3% (neurologic 1%, cardiac 5%, others 3.3%), MI 2.5% and ipsilateral stroke 3.5%. The target lesion revascularisation rate was 1.3% and the target vessel revascularisation rate 0.5%.

In November last year Medtronic announced the first patient to be enrolled in the MAVErIC III clinical trial, to include 413 high-risk patients at 35 investigational sites in North America. The MAVErIC III trial will primarily test the combination of the Exponent self-expanding carotid stent with the Interceptor PLUS carotid filter system.

SAPPHIRE

Ken Ouriel, Cleverland, US, presented late results of the Stenting and Angioplasty with Protection in Patients at HIgh Risk for Endarterectomy (SAPPHIRE) trial. SAPPHIRE is the first multicentre, randomized study comparing carotid artery stenting with embolic protection and carotid endarterectomy in high-risk surgical patients.

Carotid artery stenting had a lower rate of major adverse event at both 360 days (12.2%) and 720 days (19.6%) than carotid endarterectomy (20.1% at 360 days and 26.4% at 720 days), as well as a lower target lesion re-treatment (target lesion revascularisation) rate of 0.6% at 360 days and 1.4% at 720 days compared to carotid endarterectomy (4.3% at 360 days and 6.1% at 720 days).

Ouriel concluded the results of carotid stenting were not inferior to those of carotid endarterectomy in high-risk symptomatic and symptomatic patients, and that restenosis as measured by the rate of re-intervention is less frequent after stenting than after endarterectomy. He also stressed that these findings persist to at least two years of follow-up.

MIMIC

Dr Justine Reise, Department of Vascular Surgery, Imperial College, London, UK, presented an overview from the Mild to Moderate Intermittent Claudication (MIMIC) Trials. The trial is funded by the Camelia Botnar Arterial Research Foundation with contributions from Bard, Boston Scientific and Cook.

The MIMIC Trial is seeking to determine whether angioplasty offers adjuvant benefit over best medical treatment and supervised exercise training in mild to moderate intermittent claudication patients. There is currently no evidence of efficacy of angioplasty in the femoro-popliteal segment over and above supervised exercise training.

The MIMIC design trial includes patients with intermittent claudication ABPI < 0.9 or ABPI > 0.9 with positive stress test. The patients will undergo an assessment by Duplex mapping or diagnostic arteriography. The aorto-iliac patients (n=170) will be randomised to receive best medical and supervised exercise and balloon angioplasty or best medical and supervised exercise and no angioplasty. In addition, the femoropopliteal patients (n=170) will be randomised to receive best medical and supervised exerciseand balloon angioplasty, or best medical and supervised exercise and no angioplasty. The primary endpoint is Absolute Walking Distance (AWD) on a fixed load treadmill at two years. Secondary endpoints include: Specific – Charing Cross Claudication Questionnaire; Generic – EuroQol and SF-36; and patency and revascularisation rates.

The trial is currently enrolling patients at nine centres in the UK, with an additional nine potential new centres.