title: Transcranial laser therapy in acute stroke treatment: results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial.
abstract: OBJECTIVE
  On the basis of phase II trials, we considered that transcranial laser therapy could have neuroprotective effects in patients with acute ischemic stroke.
  
  
  METHODS
  We studied transcranial laser therapy in a double-blind, sham-controlled randomized clinical trial intended to enroll 1000 patients with acute ischemic stroke treated ≤24 hours after stroke onset and who did not undergo thrombolytic therapy. The primary efficacy measure was the 90-day functional outcome as assessed by the modified Rankin Scale, with hierarchical Bayesian analysis incorporating relevant previous data. Interim analyses were planned after 300 and 600 patients included.
  
  
  RESULTS
  The study was terminated on recommendation by the Data Monitoring Committee after a futility analysis of 566 completed patients found no difference in the primary end point (transcranial laser therapy 140/282 [49.6%] versus sham 140/284 [49.3%] for good functional outcome; modified Rankin Scale, 0-2). The results remained stable after inclusion of all 630 randomized patients (adjusted odds ratio, 1.024; 95% confidence interval, 0.705-1.488).
  
  
  CONCLUSIONS
  Once the results of the interim futility analysis became available, all study support was immediately withdrawn by the capital firms behind PhotoThera, and the company was dissolved. Proper termination of the trial was difficult but was finally achieved through special efforts by former employees of PhotoThera, the CRO Parexel and members of the steering and the safety committees. We conclude that transcranial laser therapy does not have a measurable neuroprotective effect in patients with acute ischemic stroke when applied within 24 hours after stroke onset.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT01120301.
authors.affiliation: From the Department of Neurology, Heidelberg University, Heidelberg, Germany (W.H.); Department of Neurology, Johannes Wesling Klinikum Minden, Minden, Germany (P.D.S.); Department of Neurology, Stanford Stroke Center, Palo Alto, CA (G.W.A.); Department of Neurology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel (N.M.B.); Department of Internal Medicine, Sahlgrenski University Hospital Östra, Göteborg University, Göteborg, Sweden (B.L.D.); Institute of Cardiovascular and Medical Sciences, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (R.F., K.R.L.); Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia (S.E.K.); Division of Neurology, University of Alberta, Edmonton, Alberta, Canada (A.S.); Banyan Biomarkers, San Diego, CA (S.P.R.); Allergen Research Cooperation, San Mateo, CA (S.G.D.); and Department of Neurology, School of Medicine, University of California, San Diego (J.Z.). werner.hacke@med.uni-heidelberg.de.
authors.forename: Werner
authors.initials: W
authors.lastname: Hacke
authors.affiliation: From the Department of Neurology, Heidelberg University, Heidelberg, Germany (W.H.); Department of Neurology, Johannes Wesling Klinikum Minden, Minden, Germany (P.D.S.); Department of Neurology, Stanford Stroke Center, Palo Alto, CA (G.W.A.); Department of Neurology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel (N.M.B.); Department of Internal Medicine, Sahlgrenski University Hospital Östra, Göteborg University, Göteborg, Sweden (B.L.D.); Institute of Cardiovascular and Medical Sciences, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (R.F., K.R.L.); Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia (S.E.K.); Division of Neurology, University of Alberta, Edmonton, Alberta, Canada (A.S.); Banyan Biomarkers, San Diego, CA (S.P.R.); Allergen Research Cooperation, San Mateo, CA (S.G.D.); and Department of Neurology, School of Medicine, University of California, San Diego (J.Z.).
authors.forename: Peter D
authors.initials: PD
authors.lastname: Schellinger
authors.affiliation: From the Department of Neurology, Heidelberg University, Heidelberg, Germany (W.H.); Department of Neurology, Johannes Wesling Klinikum Minden, Minden, Germany (P.D.S.); Department of Neurology, Stanford Stroke Center, Palo Alto, CA (G.W.A.); Department of Neurology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel (N.M.B.); Department of Internal Medicine, Sahlgrenski University Hospital Östra, Göteborg University, Göteborg, Sweden (B.L.D.); Institute of Cardiovascular and Medical Sciences, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (R.F., K.R.L.); Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia (S.E.K.); Division of Neurology, University of Alberta, Edmonton, Alberta, Canada (A.S.); Banyan Biomarkers, San Diego, CA (S.P.R.); Allergen Research Cooperation, San Mateo, CA (S.G.D.); and Department of Neurology, School of Medicine, University of California, San Diego (J.Z.).
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Albers
authors.affiliation: From the Department of Neurology, Heidelberg University, Heidelberg, Germany (W.H.); Department of Neurology, Johannes Wesling Klinikum Minden, Minden, Germany (P.D.S.); Department of Neurology, Stanford Stroke Center, Palo Alto, CA (G.W.A.); Department of Neurology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel (N.M.B.); Department of Internal Medicine, Sahlgrenski University Hospital Östra, Göteborg University, Göteborg, Sweden (B.L.D.); Institute of Cardiovascular and Medical Sciences, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (R.F., K.R.L.); Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia (S.E.K.); Division of Neurology, University of Alberta, Edmonton, Alberta, Canada (A.S.); Banyan Biomarkers, San Diego, CA (S.P.R.); Allergen Research Cooperation, San Mateo, CA (S.G.D.); and Department of Neurology, School of Medicine, University of California, San Diego (J.Z.).
authors.forename: Natan M
authors.initials: NM
authors.lastname: Bornstein
authors.affiliation: From the Department of Neurology, Heidelberg University, Heidelberg, Germany (W.H.); Department of Neurology, Johannes Wesling Klinikum Minden, Minden, Germany (P.D.S.); Department of Neurology, Stanford Stroke Center, Palo Alto, CA (G.W.A.); Department of Neurology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel (N.M.B.); Department of Internal Medicine, Sahlgrenski University Hospital Östra, Göteborg University, Göteborg, Sweden (B.L.D.); Institute of Cardiovascular and Medical Sciences, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (R.F., K.R.L.); Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia (S.E.K.); Division of Neurology, University of Alberta, Edmonton, Alberta, Canada (A.S.); Banyan Biomarkers, San Diego, CA (S.P.R.); Allergen Research Cooperation, San Mateo, CA (S.G.D.); and Department of Neurology, School of Medicine, University of California, San Diego (J.Z.).
authors.forename: Bjorn L
authors.initials: BL
authors.lastname: Dahlof
authors.affiliation: From the Department of Neurology, Heidelberg University, Heidelberg, Germany (W.H.); Department of Neurology, Johannes Wesling Klinikum Minden, Minden, Germany (P.D.S.); Department of Neurology, Stanford Stroke Center, Palo Alto, CA (G.W.A.); Department of Neurology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel (N.M.B.); Department of Internal Medicine, Sahlgrenski University Hospital Östra, Göteborg University, Göteborg, Sweden (B.L.D.); Institute of Cardiovascular and Medical Sciences, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (R.F., K.R.L.); Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia (S.E.K.); Division of Neurology, University of Alberta, Edmonton, Alberta, Canada (A.S.); Banyan Biomarkers, San Diego, CA (S.P.R.); Allergen Research Cooperation, San Mateo, CA (S.G.D.); and Department of Neurology, School of Medicine, University of California, San Diego (J.Z.).
authors.forename: Rachael
authors.initials: R
authors.lastname: Fulton
authors.affiliation: From the Department of Neurology, Heidelberg University, Heidelberg, Germany (W.H.); Department of Neurology, Johannes Wesling Klinikum Minden, Minden, Germany (P.D.S.); Department of Neurology, Stanford Stroke Center, Palo Alto, CA (G.W.A.); Department of Neurology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel (N.M.B.); Department of Internal Medicine, Sahlgrenski University Hospital Östra, Göteborg University, Göteborg, Sweden (B.L.D.); Institute of Cardiovascular and Medical Sciences, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (R.F., K.R.L.); Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia (S.E.K.); Division of Neurology, University of Alberta, Edmonton, Alberta, Canada (A.S.); Banyan Biomarkers, San Diego, CA (S.P.R.); Allergen Research Cooperation, San Mateo, CA (S.G.D.); and Department of Neurology, School of Medicine, University of California, San Diego (J.Z.).
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kasner
authors.affiliation: From the Department of Neurology, Heidelberg University, Heidelberg, Germany (W.H.); Department of Neurology, Johannes Wesling Klinikum Minden, Minden, Germany (P.D.S.); Department of Neurology, Stanford Stroke Center, Palo Alto, CA (G.W.A.); Department of Neurology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel (N.M.B.); Department of Internal Medicine, Sahlgrenski University Hospital Östra, Göteborg University, Göteborg, Sweden (B.L.D.); Institute of Cardiovascular and Medical Sciences, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (R.F., K.R.L.); Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia (S.E.K.); Division of Neurology, University of Alberta, Edmonton, Alberta, Canada (A.S.); Banyan Biomarkers, San Diego, CA (S.P.R.); Allergen Research Cooperation, San Mateo, CA (S.G.D.); and Department of Neurology, School of Medicine, University of California, San Diego (J.Z.).
authors.forename: Ashfaq
authors.initials: A
authors.lastname: Shuaib
authors.affiliation: From the Department of Neurology, Heidelberg University, Heidelberg, Germany (W.H.); Department of Neurology, Johannes Wesling Klinikum Minden, Minden, Germany (P.D.S.); Department of Neurology, Stanford Stroke Center, Palo Alto, CA (G.W.A.); Department of Neurology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel (N.M.B.); Department of Internal Medicine, Sahlgrenski University Hospital Östra, Göteborg University, Göteborg, Sweden (B.L.D.); Institute of Cardiovascular and Medical Sciences, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (R.F., K.R.L.); Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia (S.E.K.); Division of Neurology, University of Alberta, Edmonton, Alberta, Canada (A.S.); Banyan Biomarkers, San Diego, CA (S.P.R.); Allergen Research Cooperation, San Mateo, CA (S.G.D.); and Department of Neurology, School of Medicine, University of California, San Diego (J.Z.).
authors.forename: Steven P
authors.initials: SP
authors.lastname: Richieri
authors.affiliation: From the Department of Neurology, Heidelberg University, Heidelberg, Germany (W.H.); Department of Neurology, Johannes Wesling Klinikum Minden, Minden, Germany (P.D.S.); Department of Neurology, Stanford Stroke Center, Palo Alto, CA (G.W.A.); Department of Neurology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel (N.M.B.); Department of Internal Medicine, Sahlgrenski University Hospital Östra, Göteborg University, Göteborg, Sweden (B.L.D.); Institute of Cardiovascular and Medical Sciences, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (R.F., K.R.L.); Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia (S.E.K.); Division of Neurology, University of Alberta, Edmonton, Alberta, Canada (A.S.); Banyan Biomarkers, San Diego, CA (S.P.R.); Allergen Research Cooperation, San Mateo, CA (S.G.D.); and Department of Neurology, School of Medicine, University of California, San Diego (J.Z.).
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Dilly
authors.affiliation: From the Department of Neurology, Heidelberg University, Heidelberg, Germany (W.H.); Department of Neurology, Johannes Wesling Klinikum Minden, Minden, Germany (P.D.S.); Department of Neurology, Stanford Stroke Center, Palo Alto, CA (G.W.A.); Department of Neurology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel (N.M.B.); Department of Internal Medicine, Sahlgrenski University Hospital Östra, Göteborg University, Göteborg, Sweden (B.L.D.); Institute of Cardiovascular and Medical Sciences, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (R.F., K.R.L.); Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia (S.E.K.); Division of Neurology, University of Alberta, Edmonton, Alberta, Canada (A.S.); Banyan Biomarkers, San Diego, CA (S.P.R.); Allergen Research Cooperation, San Mateo, CA (S.G.D.); and Department of Neurology, School of Medicine, University of California, San Diego (J.Z.).
authors.forename: Justin
authors.initials: J
authors.lastname: Zivin
authors.affiliation: From the Department of Neurology, Heidelberg University, Heidelberg, Germany (W.H.); Department of Neurology, Johannes Wesling Klinikum Minden, Minden, Germany (P.D.S.); Department of Neurology, Stanford Stroke Center, Palo Alto, CA (G.W.A.); Department of Neurology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel (N.M.B.); Department of Internal Medicine, Sahlgrenski University Hospital Östra, Göteborg University, Göteborg, Sweden (B.L.D.); Institute of Cardiovascular and Medical Sciences, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (R.F., K.R.L.); Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia (S.E.K.); Division of Neurology, University of Alberta, Edmonton, Alberta, Canada (A.S.); Banyan Biomarkers, San Diego, CA (S.P.R.); Allergen Research Cooperation, San Mateo, CA (S.G.D.); and Department of Neurology, School of Medicine, University of California, San Diego (J.Z.).
authors.forename: Kennedy R
authors.initials: KR
authors.lastname: Lees
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D023381:Endpoint Determination / Q000379:methods / Q000592:standards*; D005260:Female; D006801:Humans; D053685:Laser Therapy / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D061214:Patient Safety / Q000592:standards*; D020521:Stroke / Q000175:diagnosis / Q000628:therapy*; D016896:Treatment Outcome
keywords: acute ischemic stroke; clinical trials, phase III; transcranial laser therapy