London, United Kingdom 2013 2 Large clinical trials (RCTs) C 11:45 - 12:00 Transcranial Laser Therapy (TLT) for acute Ischemic stroke. Results of NEST 3, a pivotal phase III randomized clinical trial (RCT) W. Hacke1, P.D. Schelinger2, G.W. Albers3, N.M. Bornstein4, B.S. Dahlof5, S.E. Kasner6, G. Howard7, A. Shuaib8, S.P. Richieri9, S.G. Dilly10, J. Zivin11 Dept. of Neurology, University of Heidelberg, Heidelberg, GERMANY1,Dept. of Neurolo-gy, JW Clinic Minden, Minden, GERMANY2, Stanford University Medical Center, Palo Alto, USA3, Sourasky Medical Center, Tel Aviv, ISRAEL4, Sahlgrenski University Hospital, Gote-burg, SWEDEN5, Hospital of University of Pennsylvania, Philadelphia, USA6, University of Alabama, Birmingham, USA7, University of Alberta Hospital, Edmonton, CANADA8, Banyan Biomarkers, Alachua, USA9, PhotoThera, Carlsbad, USA10, Dep. of Neurology, UCSD San Diego, San Diego, USA11 Introduction: Transcranial Laser Therapy (TLT) with a 808nm near infrared laser device stimu-lates mitochondrial energy production. Based on previous animal and clinical research TLT was investigated for the treatment of acute ischemic stroke. Two RCTs, NEST 1 (PHASE II, 120 patients) and NEST 2 (PHASE IIb, 600 patients) suggested a clinically meaningful benefit for acute stroke patients. NEST 3 was the pivotal Phase III trial of TLT for acute ischemic stroke. Methods and Patients: NEST 3 was a double blind RCT planned for recruitment of 1,000 pa-tients in 48 centers and 10 countries. Inclusion criteria were ischemic stroke within 24h, NI-HSSS 7-17 up to 80 years without rt-PA therapy. Interim analyses for safety, futility or over-whelming efficacy were predefined. Results: Between September 2010 and October 2012 a total of 646 patients were randomized. An pre-specified interim efficacy analysis was to be conducted on 90-day outcome data from the first 600 patients. In preparation for this, a futility analysis performed by the DMC on 90- day outcome data from the first 566 randomized patients led to termination of the trial due to futility albeit without any safety concerns. The data are currently being thoroughly analyzed. We will report all primary and secondary endpoint data in the futility data set (N=566), addi-tional safety data of all hitherto recruited patients (N=646), and a pooled analysis using out-come data from all NEST trials 1-3. Conclusion: NEST 3 failed to show a benefit of TLT over sham procedure and was terminated for futility after inclusion of 2 thirds of the planned patient number. Cerebrovasc Dis 2013; 35 (suppl 3)1-854 191 10:30-12:50 Oral Session Auditorium Large clinical trials 3 Chairs: M. Brainin, Austria and M. Ginsberg, USA 1 Large clinical trials (RCTs) C 11:30 - 11:45 ARUBA (A Randomized trial of Unruptured Brain Arteriovenous malformations) J.P. Mohr1, C. Stapf2, A.J. Moskowitz3, M.K. Parides4, E. Moquete5, W.L. Young6, C.S. Moy7, E. Vicaut8 On behalf of the 35 Centers in North/South America, Europe, Korea, and Australia Neurological Institute, NYC, New York, USA1,APHP Hop Lariboisiére, Paris, FRANCE2, In- CHOIR, Mt Sinai Medical Center, New York, USA3, InCHOIR, Mt Sinai Medical Center, New York, USA4, InCHOIR, Mt Sinai Medical Center, New York, USA5, Univ Calif, San Francisco, USA6, NINDS, NIH, Bethesda, , USA7, APHP Hop Lariboisiére, Paris, FRANCE8 PURPOSE The literature offers no controlled treatment data for comparison of any of the treatments, im-mediate or deferred, for the benefit of preventive therapy for unruptured BAVMs PRIMARY AIM: To determine whether medical management alone is superior, or not inferior, to invasive therapy in averting death (any cause) or stroke (symptomatic hemorrhage or infarction). SECONDARY AIM: To determine whether treatment of unruptured BAVMs by medical man-agement alone offers a lower risk of death or clinical impairment (Rankin Score >/= 2) at 5 years post-randomization compared to invasive therapy. METHODS A prospective randomized clinical trial, SAMPLE SIZE: 225 patients (1:1 random assignment). PATIENTS aged ≥18 years, diagnosed by imaging with an unruptured BAVM considered by the local investigators to be suitable for attempted eradication. OUTCOME MEASURES: The primary outcome is the composite event of death from any cause or stroke (hemorrhage or infarction confirmed by imaging). Clinical outcome is measured by the Rankin Scale, NIHSS, SF-36, and EuroQol. INTERVENTIONS: Patients have been randomly assigned to best possible invasive therapy (medical management plus endovascular, surgical, and/or radiation therapy) versus medical management alone. FOLLOW-UP planned for 5-10 years from randomization. RESULTS/TRIAL STATUS 223 patients have been randomized as of Feb 2013. In July 2013 ARUBA will have finished the enrollment and entered the follow-up only. An NINDS-appointed Data & Safety Monitoring Board endorsed the sample size and continua-tion plans. Interim results to be presented at the ESC.
Karger_ESC London_2013
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