SAN DIEGO—Although transcranial laser therapy performed within 24 hours of stroke onset was safe and well tolerated, the primary efficacy end point of a favorable 90-day outcome on the modified Rankin Scale (mRS) was not achieved, reported Justin A. Zivin, MD, PhD, at the 2009 International Stroke Conference. However, some improvement was observed in a subset of patients with moderate to moderately severe stroke. Findings from the double-blind, randomized controlled trial were also published in the February 20 online Stroke.
Testing Laser Therapy in a Broad Range of Patients
The NeuroThera Effectiveness and Safety Trial–2 (NEST-2) included a larger number and broader range of patients than NEST-1. A total of 660 patients with acute ischemic stroke (ages 40 to 90) were randomized to sham therapy (n = 329) or transcranial laser therapy (n = 331) via the NeuroThera Laser System, which uses a near-infrared (808 nm), nonionizing wavelength that is invisible to the naked eye. Due to technical difficulties, only 327 patients were included in the sham group. All patients had their scalps shaved to allow optimal amounts of laser energy to penetrate the brain. Each two-minute treatment was performed at 20 predetermined locations on the scalp, regardless of stroke location.
Baseline characteristics, such as age, ethnicity, time to treatment, and history of diabetes, hypertension, atrial fibrillation, and smoking, were similar between the laser and sham therapy groups. All patients were diagnosed with ischemic stroke within 24 hours of onset and had a baseline NIH Stroke Scale (NIHSS) score between 7 and 22. Mean baseline NIHSS scores were 13.1 for the transcranial laser therapy group and 13.2 for the sham group; median baseline NIHSS scores were 12 and 13, respectively. “The median NIHSS scores were in the range that we have commonly seen in our recent trials, so there was no major difference in that way,” noted Dr. Zivin, Professor of Neurosciences of the Department of Neurosciences at the University of California at San Diego. “However, the time to treatment in both groups was a bit over 14.5 hours.”
Patients were excluded if they had received therapies such as t-PA or any type of head implants, showed evidence of hemorrhage, had a prestroke score of 3 or greater on the mRS, or had uncontrollable blood glucose or blood pressure. The primary efficacy end point was a score of 0 to 2 on the mRS at 90 days. Secondary end points included an overall shift in mRS and NIHSS scores.
Some Patients May Benefit From Laser Therapy
At 90 days, 36.3% (n = 120) of patients in the transcranial laser therapy group achieved an mRS score of 0 to 2, compared with 30.9% (n = 101) of those in the sham group. “Looking at the shift in the distribution of the scores, you can see that all of the scores were better than or equal to the scores in the sham group. In particular, there was no difference in the really bad outcomes,” Dr. Zivin stated.
Logistic regression analysis with additional covariates showed a treatment odds ratio of 1.34. All covariates were statistically significant, except for gender and history of stroke. A nonsignificant trend toward better outcomes with transcranial laser treatment was observed on the shift test, which was stratified for the baseline severity and the time from stroke onset to time of randomization. “In all cases, the subset analysis favored the treatment with one exception, which was really bad initial stroke scale scores,” noted Dr. Zivin.
Patients with severe strokes had a dichotomous mRS success rate of 8% (transcranial laser therapy, 7%; sham, 9.1%). When analyses were restricted to those with moderate to moderately severe stroke, a significant beneficial effect was observed. In these patients, “the dichotomous mRS success rate of transcranial laser therapy showed an absolute improvement rate of 9.7% (transcranial laser therapy, 51.6%; sham, 41.9%),” said Dr. Zivin and his coauthors. “Had those patients [with severe stroke] been eliminated from the trial, the difference between the sham treatment [and transcranial laser therapy treatment] would have been almost 10%,” commented Dr. Zivin. A similar beneficial effect was seen in the NEST-1 trial.
Rates of mortality and serious adverse events were similar between the groups. Adverse events were reported by 92.7% of the treatment group and 93.6% of the sham group. The transcranial laser treatment group reported 58 deaths and 125 serious adverse events, while the sham group reported 57 deaths and 137 serious adverse events. However, “no serious adverse events were directly attributable to transcranial laser treatment,” stated Dr. Zivin and colleagues. Hemorrhagic transformation at day 5 occurred in 14.8% of patients (n = 49) in the treatment group and in 17.1% of patients (n = 56) in the sham group.