XVII. European Stroke Conference
Nice, France
XVII. European Stroke Conference
Nice, France
Oral Session:
Large clinical trials (RCTs) I
Date:
Wednesday14 May 2008
Time:
11:00 - 11:15
- Room:
Apollon
Chair: F. Aichner, Austria and JP Mohr, USA
01
PREVENTION REGIMEN FOR EFFECTIVELY AVOIDING SECOND STROKES (PRoFESS) TRIAL: COMPARISON OF A FIXED-DOSE COMBINATION OF EXTENDED-RELEASE DIPYRIDAMOLE PLUS ASA WITH CLOPIDOGREL
R. Sacco
H.-C. Diener
S. Yusuf
for the Steering Committee and PRoFESS Study Group
University of Miami, Miami
USA
Background: There is a high risk of recurrent stroke following an initial stroke or transient ischaemic attack. A combination of acetylsalicylic acid (ASA) and extended release dipyridamole (ER-DP) or clopidogrel were superior to ASA in secondary stroke prevention trials. The Prevention Regimen for Effectively Avoiding Secondary Strokes (PRoFESS) trial, the largest secondary stroke prevention trial to date, investigated whether the fixed-dose combination of ASA plus ER-DP compared to clopidogrel reduced the risk of recurrent strokes. Methods: Patients aged 50 years or older with an ischaemic stroke within 120 days who were stable were included. A 2 x 2 factorial design was used to compare the fixed-dose combination of ASA (25 mg) plus ER-DP (200 mg) given twice daily, to once-daily clopidogrel (75 mg) and telmisartan to placebo. The primary endpoint was time to recurrent stroke. Results: 20,333 patients (mean age 66.1 +/- 8.6 years; 36.0% female) were recruited from 695 sites in 35 countries/regions. Median time from ischaemic stroke to randomisation was 15 days; 39.9% of patients were randomised within 10 days. Further results will be presented at the meeting. Discussion: The results from this direct comparison of antiplatelet regimens will help clarify the optimal management of recurrent stroke in the future.
Large clinical trials (RCTs) I
Date:
Wednesday14 May 2008
Time:
11:15 - 11:30
- Room:
Apollon
Chair: F. Aichner, Austria and JP Mohr, USA
02
PREVENTION REGIMEN FOR EFFECTIVELY AVOIDING SECOND STROKES (PRoFESS) TRIAL: TELMISARTAN VERSUS PLACEBO
S. Yusuf
R. Sacco
H.-C. Diener
for the Steering Committee and PRoFESS Study Group
McMaster University, Hamilton
CANADA
Background: The risk of recurrent stroke may be reduced by blocking the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptors blockers (ARBs). Furthermore, evidence suggests that ACE inhibitors and ARBs reduce the risk of stroke through mechanisms independent of their blood pressure lowering effects. The largest secondary stroke prevention trial to date, Prevention Regimen for Effectively Avoiding Secondary Strokes (PRoFESS), investigated in a placebo-controlled trial whether telmisartan in addition to usual care reduced the risk of further strokes. Methods: Patients aged 50 years or older with an ischaemic stroke within 120 days who were stable were included in the trial. A 2 x 2 factorial design was used to compare the fixed-dose combination of ASA (25 mg) plus extended-release dipyridamole (ER-DP, 200 mg), given twice daily, to once-daily clopidogrel (75 mg), and once-daily telmisartan (80 mg) compared with placebo. Primary endpoint was time to recurrent stroke. Results: A total of 20,333 patients, 36.0% female and a mean age of 66.1 +/- 8.6 years were recruited from 35 countries. At baseline the mean blood pressure was 144/84 mm Hg and 36.8% of patients were receiving an ACE inhibitor. 39.9% of patients were randomised within 10 days; median time from ischaemic stroke to randomisation was 15 days. Further results will be presented at the meeting. Discussion: The results from PRoFESS will elucidate the role of telmisartan in addition to usual care in the prevention of recurrent stroke.
Large clinical trials (RCTs) I
Date:
Wednesday14 May 2008
Time:
11:30 - 11:45
- Room:
Apollon
Chair: F. Aichner, Austria and JP Mohr, USA
03
PREVENTION REGIMEN FOR EFFECTIVELY AVOIDING SECOND STROKES (PRoFESS) TRIAL: COGNITIVE AND FUNCTIONAL OUTCOMES AFTER STROKE
H.-C.Diener
S Yusuf
R Sacco
for the Steering Committee and PRoFESS Study Group
University Duisburg-Essen
GERMANY
Background: Stroke is the number one cause of neurological disability worldwide, therefore secondary prevention of stroke is critical from a quality of life perspective. The Prevention Regimen for Effectively Avoiding Secondary Strokes (PRoFESS) trial is the largest secondary stroke prevention trial to date, and investigated whether the fixed-dose combination of acetylsalicylic acid (ASA) plus extended-release dipyridamole (ER-DP) compared to clopidogrel, and telmisartan compared to usual care reduced the risk of further strokes. Angiotensin II receptor blockers are neuroprotective in animal models of stroke, and can theoretically reduce the risk of vascular dementia or severity of a recurrent stroke. Also there are experimental data to suggest that dipyridamole may have an effect on cognitive decline in dementia due to subcortical ischaemia through several mechanisms including: prevention of new vascular lesions; anti-oxidant and anti-inflammatory effects; and an increase in cerebral perfusion. Therefore the effect of telmisartan and ASA plus ER-DP on both the severity of recurrent stroke, and cognitive function were assessed. Methods: Patients aged 50 years or older with an ischaemic stroke within 120 days and who where stable were included in the trial. A fixed-dose combination of ASA (25 mg) plus ER-DP (200 mg), given twice daily, compared to once-daily clopidogrel (75 mg), and telmisartan (80 mg once daily) compared with placebo were investigated using a 2 x 2 factorial study design. Severity of recurrent stroke was assessed by modified Rankin. Cognitive function was assessed by serial changes in Mini Mental State Examination. Results: Results will be presented at the meeting.
Large clinical trials (RCTs) I
Date:
Wednesday14 May 2008
Time:
11:45 - 12:00
- Room:
Apollon
Chair: F. Aichner, Austria and JP Mohr, USA
04
Endarterectomy versus Angioplasty in patients with Symptomatic Severe carotid Stenosis (EVA-3S, NCT00190398): final results
J.L.Mas
for the EVA-3S investigators
Hôpital Sainte-Anne
FRANCE
Background. Carotid angioplasty and stenting (CAS) is less invasive than carotid endarterectomy (CEA), but it is unclear whether it is as safe as surgery and provides a degree of long-term protection against ipsilateral stroke similar to that of surgery. Methods. We conducted a multicenter, randomized, noninferiority trial (EVA-3S) to compare CAS with CEA in patients with a recently (< 4 months) symptomatic atherosclerotic carotid stenosis of at least 60%. Operator experience had to be substantiated through documentation of a sufficient number of cases performed. In most patients, carotid stenting was performed with the use of cerebral protection devices. Patients were followed up by the study neurologist at 1 month, 6 months and every 6 months thereafter for a maximum of 5 years. The primary endpoints were: (a) any stroke or death within 30 days of the procedure and (b) any stroke or death within 30 days plus ipsilateral stroke during follow-up. Secondary endpoints included: (a) other events within 30 days of the procedure; (b) any disabling stroke or death within 30 days plus disabling or fatal ipsilateral stroke during follow-up; (c) any stroke or death; (d) carotid restenosis. Cumulative survival rates and hazard functions were estimated using Kaplan-Meier method. Differences between groups were assessed using log rank test. Data were analyzed according to the intention-to-treat principle. Results. The trial was stopped prematurely after the inclusion of 527 patients for reasons of both safety and futility. The 30-day risk of any stroke or death was significantly higher after stenting (9.6%) than after endarterectomy (3.9%), resulting in a relative risk of 2.5 (95% CI, 1.2 to 5.1). Long-term outcomes after a mean follow-up of more than 3 years will be presented.
Large clinical trials (RCTs) I
Date:
Wednesday14 May 2008
Time:
12:00 - 12:15
- Room:
Apollon
Chair: F. Aichner, Austria and JP Mohr, USA
05
Two Year Results of the SPACE Study
(Stent-protected Percutaneous Angioplasty of the Carotid vs. Endarterectomy)
P.A.Ringleb
for the SPACE-Collaborative Group
University of Heidelberg
GERMANY
Background: SPACE was a multinational, prospective, randomized trial testing the hypothesis that carotid artery stenting (CAS) is not inferior to carotid endarterectomy (CEA) in treating patients with symptomatic carotid artery stenosis. Primary endpoint was the composite of ipsilateral stroke or death up to 30days. SPACE failed to prove non-inferiority regarding this endpoint (absolute difference 0.47; 95%CI -2.41 to +3.35; P=0.09). One year results for the composite endpoint ipsilateral ischemic stroke or vascular death have been presented in 2007. According to the protocol of SPACE, the principal secondary endpoint is assessed at 2 years. In addition, further secondary endpoints including re-stenosis are assessed at this point. The two year follow up will be completed in March 2008. Results: We will report the 2 year results for the principal secondary endpoint, and the results of other secondary and tertiary endpoints of SPACE, including the rate of any stroke and the incidence of re-stenoses. The results will be available in April 2008. Summary: After 30 days, SPACE failed to proof non-inferiority of CAS compared to CEA with respect to the periprocedural complication rate. Despite a significantly increased restenosis-rate in patients treated with CAS the rate of recurrent stroke and death up to one year was very low and not different between both treatment modalities. The 2 year final results will be presented in detail and discussed thoroughly.
Large clinical trials (RCTs) I
Date:
Wednesday14 May 2008
Time:
12:15 - 12:30
- Room:
Apollon
Chair: F. Aichner, Austria and JP Mohr, USA
06
Final Results CLEARIVH Trial: clot lysis, safety and 30 day functional outcomes
D.F.Hanley
for the Clear IVH investigators
Johns Hopkins Brain Injury Outcomes Division
USA
Intraventricular hemorrhage (IVH) is a major intracerebral hemorrhage (ICH) severity factor and appears to be an important treatment target (STICH, fVIIa trials). While substantial reduction in predicted mortality appears achievable with catheter-based clot lysis treatment limited multi-site, international, prospective assessments of this treatment have been performed. A safety trial has demonstrated rt-PA enhanced daily clot lysis, but the dose-response relationship(s) between rt-PA and overall clot lysis rate (CT) have not been tested. Similarly, the safety of various lower doses (0.6mg, 2.0 mg and 3.0mg / day) has not been explored. CLEAR IVH A (n=16) tested dose-response for rt-PA mediated clearance of blood from the ventricular system. Clear B (n=36) tested for benefit of more frequent dosing. CLEAR IVH B tested shorter dose intervals (Q80 vs. Q120). Subjects were treated 4 days or until 3rd and 4th ventricles opened and lateral shift was reduced. By February 2008 CLEAR A & B will have completed accrual of 52 patients meeting I/E criteria (ICH <30 cc, large IVH, EVD, 6-hr stability CT). Data will be monitored and reviewed by independent DSMB. Median clinical severity will be determined for important domains (admit BP, GCS, age, ICH volume, IVH volume). ICH location, hypertension, drug use, and ETOH will be assessed and compared to the prior safety study (n=48). Primary outcome is CT and safety; secondary outcomes are mRS and GOS at days 30, 90, and 180. To assess the effect of drug delivery site on clot lysis, we will compare CT to rate of clot lysis in the 3rd and 4th ventricular regions (Cr) closest to the extra ventricular drainage (EVD). Safety limits for DSMB review were constant for CLEAR A & B studies: mortality (55%), rebleeding (35%) and ventriculitis (30%). No safety threshold was crossed in CLEAR IVH current rates (n= 49): 30 day mortality (14%), rebleeding (6%) and bacterial ventriculitis (4%). Detailed final results of CLEAR IVH will be presented.
