There were similar safety outcomes and no significant differences in functional independence with endovascular therapy after intravenous tissue plasminogen activator (t-PA), as compared with intravenous t-PA alone in patients with moderate-to-severe acute ischemic stroke. The IMS III trial, which was stopped early due to “futility,” was published Feb. 7 ahead of print in the New England Journal of Medicine.

Endovascular therapy recanalizes occlusions in large arteries more frequently and rapidly than intravenous t-PA in patients with acute ischemic stroke and is increasingly used to treat patients with occlusions of the large intracranial arteries in institutions with required expertise (Circulation 2011;123:2591-2601). However, the study authors said there is an absence of data from a randomized trial, so the benefit of the combination therapy is “uncertain.”

In this international, Phase III, open-label trial, Joseph P. Broderick, MD, of the department of neurology at the University of Cincinnati’s Neuroscience Institute, and colleagues randomly assigned eligible patients who had received t-PA within three hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone in a 2:1 ratio.

The primary outcome measure was a modified Rankin Scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability).

Broderick et al noted that the study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). “[I]t failed to show a benefit in functional outcome with the use of additional endovascular therapy, as compared with the standard therapy of intravenous t-PA,” they wrote. The safety profiles were similar in the two treatment groups.

The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8 percent with endovascular therapy and 38.7 percent with intravenous t-PA), nor were there significant differences for the predefined subgroups of patients with a National Institutes of Health Stroke Scale score of 20 or higher (6.8 percentage points) and those with a score of 19 or lower (-1 percentage point).

The IMS III team also reported that findings in the endovascular therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1 and 21.6 percent, respectively), and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA.

The authors concluded that the use of randomization in ongoing and future stroke trials, rather than the treatment of eligible patients with endovascular therapy outside any trial, and minimization of the time to treatment will be essential for assessing the potential benefit of endovascular therapy for acute ischemic stroke.

The National Institutes of Health provided the majority of the funding for the study.