Transcranial laser therapy in acute stroke treatment: Results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial

Werner Hacke, Peter D. Schellinger, Gregory W. Albers, Natan M. Bornstein, Bjorn L. Dahlof, Rachael Fulton, Scott E. Kasner, Ashfaq Shuaib, Steven P. Richieri, Stephen G. Dilly, Justin Zivin, Kennedy R. Lees, Justin A. Zivin, Joseph Broderick, Anastasia Ivanova, Karen Johnston, Bo Norrving, Greg Albars, Andrei Alexandrov, David BrownPatrick Capone, David Chiu, Wayne Clark, Jack Cochran, Colin Deredyn, Thomas Devlin, William Hickling, George Howell, David Huang, Shazam Hussain, Sidney Mallenbaum, Majaz Moonis, Marshall Nash, Marilyn Rymer, Reid Taylor, Margaret Tremwel, Brian Buck, Julio Perez, Christian Gerloff, Bernd Greiwing, Martin Grond, Gerhard Hamman, Thomas Haarmeiter, Sebastian Jander, Martin Köhrmann, Martin Ritter, Peter Schallinger, Dietmar Schneider, Jan Sobesky, Thorsten Steiner, Helmuth Steinmetz, Roland Veltkamp, Christian Weimar, Franz Gruber, Bjorn Andersson, Lennart Welin, Didier Leys, Turgut Tatlisumak, Andreas Luft, Philippe Lyrer, Patrik Michel, Carlos Molina, Tomas Segura

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background and Purpose-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 Conclusions-Once the results of the interim futility analysis became available, all study support was immediately withdrawn by the capital firms behind PhotoThera, and the company was dissolved.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. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01120301.

Original languageEnglish (US)
Pages (from-to)3187-3193
Number of pages7
JournalStroke
Volume45
Issue number11
DOIs
StatePublished - Jan 1 2014

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Laser Therapy
Stroke
Safety
Equipment and Supplies
Medical Futility
Neuroprotective Agents
Therapeutics
Clinical Trials Data Monitoring Committees
Bayes Theorem
Thrombolytic Therapy
Randomized Controlled Trials
Odds Ratio
Economics
Clinical Trials
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

Hacke, W., Schellinger, P. D., Albers, G. W., Bornstein, N. M., Dahlof, B. L., Fulton, R., ... Segura, T. (2014). Transcranial laser therapy in acute stroke treatment: Results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial. Stroke, 45(11), 3187-3193. https://doi.org/10.1161/STROKEAHA.114.005795

Transcranial laser therapy in acute stroke treatment : Results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial. / Hacke, Werner; Schellinger, Peter D.; Albers, Gregory W.; Bornstein, Natan M.; Dahlof, Bjorn L.; Fulton, Rachael; Kasner, Scott E.; Shuaib, Ashfaq; Richieri, Steven P.; Dilly, Stephen G.; Zivin, Justin; Lees, Kennedy R.; Zivin, Justin A.; Broderick, Joseph; Ivanova, Anastasia; Johnston, Karen; Norrving, Bo; Albars, Greg; Alexandrov, Andrei; Brown, David; Capone, Patrick; Chiu, David; Clark, Wayne; Cochran, Jack; Deredyn, Colin; Devlin, Thomas; Hickling, William; Howell, George; Huang, David; Hussain, Shazam; Mallenbaum, Sidney; Moonis, Majaz; Nash, Marshall; Rymer, Marilyn; Taylor, Reid; Tremwel, Margaret; Buck, Brian; Perez, Julio; Gerloff, Christian; Greiwing, Bernd; Grond, Martin; Hamman, Gerhard; Haarmeiter, Thomas; Jander, Sebastian; Köhrmann, Martin; Ritter, Martin; Schallinger, Peter; Schneider, Dietmar; Sobesky, Jan; Steiner, Thorsten; Steinmetz, Helmuth; Veltkamp, Roland; Weimar, Christian; Gruber, Franz; Andersson, Bjorn; Welin, Lennart; Leys, Didier; Tatlisumak, Turgut; Luft, Andreas; Lyrer, Philippe; Michel, Patrik; Molina, Carlos; Segura, Tomas.

In: Stroke, Vol. 45, No. 11, 01.01.2014, p. 3187-3193.

Research output: Contribution to journalArticle

Hacke, W, Schellinger, PD, Albers, GW, Bornstein, NM, Dahlof, BL, Fulton, R, Kasner, SE, Shuaib, A, Richieri, SP, Dilly, SG, Zivin, J, Lees, KR, Zivin, JA, Broderick, J, Ivanova, A, Johnston, K, Norrving, B, Albars, G, Alexandrov, A, Brown, D, Capone, P, Chiu, D, Clark, W, Cochran, J, Deredyn, C, Devlin, T, Hickling, W, Howell, G, Huang, D, Hussain, S, Mallenbaum, S, Moonis, M, Nash, M, Rymer, M, Taylor, R, Tremwel, M, Buck, B, Perez, J, Gerloff, C, Greiwing, B, Grond, M, Hamman, G, Haarmeiter, T, Jander, S, Köhrmann, M, Ritter, M, Schallinger, P, Schneider, D, Sobesky, J, Steiner, T, Steinmetz, H, Veltkamp, R, Weimar, C, Gruber, F, Andersson, B, Welin, L, Leys, D, Tatlisumak, T, Luft, A, Lyrer, P, Michel, P, Molina, C & Segura, T 2014, 'Transcranial laser therapy in acute stroke treatment: Results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial', Stroke, vol. 45, no. 11, pp. 3187-3193. https://doi.org/10.1161/STROKEAHA.114.005795
Hacke, Werner ; Schellinger, Peter D. ; Albers, Gregory W. ; Bornstein, Natan M. ; Dahlof, Bjorn L. ; Fulton, Rachael ; Kasner, Scott E. ; Shuaib, Ashfaq ; Richieri, Steven P. ; Dilly, Stephen G. ; Zivin, Justin ; Lees, Kennedy R. ; Zivin, Justin A. ; Broderick, Joseph ; Ivanova, Anastasia ; Johnston, Karen ; Norrving, Bo ; Albars, Greg ; Alexandrov, Andrei ; Brown, David ; Capone, Patrick ; Chiu, David ; Clark, Wayne ; Cochran, Jack ; Deredyn, Colin ; Devlin, Thomas ; Hickling, William ; Howell, George ; Huang, David ; Hussain, Shazam ; Mallenbaum, Sidney ; Moonis, Majaz ; Nash, Marshall ; Rymer, Marilyn ; Taylor, Reid ; Tremwel, Margaret ; Buck, Brian ; Perez, Julio ; Gerloff, Christian ; Greiwing, Bernd ; Grond, Martin ; Hamman, Gerhard ; Haarmeiter, Thomas ; Jander, Sebastian ; Köhrmann, Martin ; Ritter, Martin ; Schallinger, Peter ; Schneider, Dietmar ; Sobesky, Jan ; Steiner, Thorsten ; Steinmetz, Helmuth ; Veltkamp, Roland ; Weimar, Christian ; Gruber, Franz ; Andersson, Bjorn ; Welin, Lennart ; Leys, Didier ; Tatlisumak, Turgut ; Luft, Andreas ; Lyrer, Philippe ; Michel, Patrik ; Molina, Carlos ; Segura, Tomas. / Transcranial laser therapy in acute stroke treatment : Results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial. In: Stroke. 2014 ; Vol. 45, No. 11. pp. 3187-3193.
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abstract = "Background and Purpose-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. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01120301.",
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T1 - Transcranial laser therapy in acute stroke treatment

T2 - Results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial

AU - Hacke, Werner

AU - Schellinger, Peter D.

AU - Albers, Gregory W.

AU - Bornstein, Natan M.

AU - Dahlof, Bjorn L.

AU - Fulton, Rachael

AU - Kasner, Scott E.

AU - Shuaib, Ashfaq

AU - Richieri, Steven P.

AU - Dilly, Stephen G.

AU - Zivin, Justin

AU - Lees, Kennedy R.

AU - Zivin, Justin A.

AU - Broderick, Joseph

AU - Ivanova, Anastasia

AU - Johnston, Karen

AU - Norrving, Bo

AU - Albars, Greg

AU - Alexandrov, Andrei

AU - Brown, David

AU - Capone, Patrick

AU - Chiu, David

AU - Clark, Wayne

AU - Cochran, Jack

AU - Deredyn, Colin

AU - Devlin, Thomas

AU - Hickling, William

AU - Howell, George

AU - Huang, David

AU - Hussain, Shazam

AU - Mallenbaum, Sidney

AU - Moonis, Majaz

AU - Nash, Marshall

AU - Rymer, Marilyn

AU - Taylor, Reid

AU - Tremwel, Margaret

AU - Buck, Brian

AU - Perez, Julio

AU - Gerloff, Christian

AU - Greiwing, Bernd

AU - Grond, Martin

AU - Hamman, Gerhard

AU - Haarmeiter, Thomas

AU - Jander, Sebastian

AU - Köhrmann, Martin

AU - Ritter, Martin

AU - Schallinger, Peter

AU - Schneider, Dietmar

AU - Sobesky, Jan

AU - Steiner, Thorsten

AU - Steinmetz, Helmuth

AU - Veltkamp, Roland

AU - Weimar, Christian

AU - Gruber, Franz

AU - Andersson, Bjorn

AU - Welin, Lennart

AU - Leys, Didier

AU - Tatlisumak, Turgut

AU - Luft, Andreas

AU - Lyrer, Philippe

AU - Michel, Patrik

AU - Molina, Carlos

AU - Segura, Tomas

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background and Purpose-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. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01120301.

AB - Background and Purpose-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. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01120301.

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