Promising safety data
There were no significant safety issues, and the risk for bleeding was not significantly increased in the tenecteplase group. Symptomatic ICH occurred in 3.2% of the TNK group versus 2.3% of the placebo group, a nonsignificant difference.
“The low rate of ICH with TNK at this late time point is very reassuring,” Dr. Albers said. “We believe the reason for the low ICH rate is probably because these patients were selected for small core strokes. We also found that there was a trend towards the most benefit from TNK in patients with the smallest cores, supporting the use of imaging to select patients.”
The secondary endpoint of complete recanalization at 24-hours post randomization was higher in the TNK group at 76.7%, compared with 63.9% in the placebo group (P = .006).
Benefit in M1 occlusions?
Subgroup analysis showed that there appeared to be a benefit of TNK in the 227 patients included who had an M1 occlusion. In this group, the common odds ratio for a more favorable outcome in the mRS shift analysis with TNK was 1.59 (95% CI, 1.00-2.52; adjusted nominal P = .051).
The percentage of patients with a favorable outcome (mRS, 0-2) at 90 days in the M1 occlusion subgroup was 45.9% for TNK versus 31.4% for placebo, giving an adjusted odds ratio of 2.03 (95% CI, 1.14-3.66; nominal P = .017).
But Dr. Albers cautioned that this was an exploratory analysis, and no formal conclusions should be drawn from these data.
“We saw very strong results in favor of giving thrombolysis in the patients with M1 occlusions. We had preliminary pilot data suggesting this approach may work in these patients,” he commented.
“But we included the smaller M2 occlusions as well, because we thought that as there should be less clot in an M2 occlusion it might be easier to dissolve with thrombolysis,” he added. “But surprisingly, the M2 occlusion patients seemed to do worse with TNK than placebo, and the M1 patients did better.”
Timing of TNK
Dr. Albers said that there was also information from in the study on the timing of TNK administration.
In patients who also received thrombectomy, who made up of the majority of those in the study, the average time of TNK administration was only 20 minutes before the thrombectomy procedure.
“We had hoped to have a longer time between thrombolysis and thrombectomy so the drug would have more time to work. The idea was that patients would be given TNK at the primary stroke center before being transferred for thrombectomy, but actually only a few patients received TNK at the primary stroke center,” Dr. Albers explained.
“But, again surprisingly, we found that patients given TNK right at the time of the thrombectomy procedure seemed to show a trend toward benefit over placebo,” he reported.
He suggested that this may be caused by the thrombolytic dissolving the small fragments that can sometimes break off and cause further occlusions when the clot is removed by thrombectomy.
“We have learned a lot from this study, and we are planning to go forward with the information gained to plan a second study, in which we will focus on patients with M1 occlusions and try to get the drug on board at primary stroke centers, so it has more time to work before thrombectomy,” he added.
Commenting on the TIMELESS study at the ESOC meeting, Georgios Tsivgoulis, MD, professor of neurology, University of Athens, said that he thought the trial had shown three important results: “Firstly, TNK appeared to be safe in this late window in these selected patients – that is a very important observation. Secondly, reperfusion rates at 24 hours were increased with TNK and we know that this translates into clinical benefit. And thirdly, there was a neutral effect on primary outcomes, but I think the sample size of 438 patients was not large enough to show efficacy.”
Dr. Tsivgoulis concluded that these points need to be addressed in future trials.
The TIMELESS trial was funded by Genentech.
A version of this article first appeared on Medscape.com.