Transcranial Laser Therapy in Acute Stroke Treatment

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 Conclusions-Once the results of the interim futility analysis became available, all study support was immediately withdrawn by the capital firms behind PhotoThera, and the company was dissolved.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. This series of basic science studies preceded 2 randomized phase IIa and IIb clinical trials, the neurothera effectiveness and safety trials (NEST)-1 and NEST 2, which included 780 patients (120 in NEST 1 and 660 in NEST 2).12,13 These provided reassuring safety data in patients, but the larger trial was neutral on efficacy end points. However, the combined data were interpreted as showing positive trends that justified definitive testing.14 From the second of these trials, a post hoc analysis identified a subgroup that was hypothesized to have higher potential for efficacy and this formed the target population for the present clinical trial. 13 We conducted a randomized trial to test for the benefit of TLT in improving the proportion of patients with good functional outcome (modified Rankin Scale [mRS], 0-2) at 90 days after stroke onset. Methods Study DesignNEST 3 was a double-blind, randomized, sham-controlled, parallel group, multicenter trial intended to enroll ≤1000 patients from ≈150 investigational sites. Patients were eligible for inclusion if they were aged 40 to 80 years, had a clinical diagnosis of acute ischemic stroke, no evidence of hemorrhagic infarct exceeding petechial bleeding along the margins, had a baseline National Instit...

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