Trial Shows Evolution of Endovascular Stroke Treatment Over Time
Acute stroke therapy changed dramatically during the course of the Interventional Management of Stroke (IMS) III trial from 2005 to 2012, resulting in several amendments to the protocol. Yet clinical outcomes did not differ between the earlier and the later parts of the study, according to an analysis published online October 16, 2014, ahead of print in Stroke.
“[T]echnology and clinical practice are likely to continue to evolve during ongoing and future acute ischemic stroke trials. Such change should be expected and monitored and its effect measured, particularly in trials that last > 2 to 3 years,” Joseph P. Broderick, MD, of the University of Cincinnati (Cincinnati, OH), and colleagues write.
| Methods |
| IMS III randomized patients to IV tissue plasminogen activator (t-PA) with or without the addition of endovascular therapy and failed to show a difference in outcomes between the 2 groups. But major changes occurred in the treatment of acute stroke from the beginning of the trial, when intraarterial t-PA was the standard endovascular therapy, to the end, when multiple thrombectomy devices were available. The protocol for the trial—which was designed to allow for the use of new devices as they became available—was amended 4 times to reflect changes in endovascular therapy in the community, covering changes in inclusion and exclusion criteria, use of devices, and t-PA dose. |
| Dr. Broderick and colleagues set out to examine shifts in the patient population and the use of endovascular therapy from the beginning to the end of the trial, comparing 610 patients treated under the first 4 protocol versions (the original plus 3 amendments) and 46 treated under the fifth and final version. |
The researchers uncovered several
differences between the 2 time periods of 2005-2011 and 2011-2012 (table 1).
In general, there were no differences in functional and safety outcomes between the 2 study arms in either time period, although among patients treated under the first 4 protocols, the addition of endovascular therapy was associated with a higher rate of recanalization as shown by 24-hour CT angiography compared with IV t-PA alone (84% vs 59%).
In patients treated under the final protocol, there was a numerically greater difference between the endovascular and control arms in the percentage of patients who had a modified Rankin Scale score ≤ 2 at 3 months and higher rates of procedural complications and asymptomatic intracerebral hemorrhages compared with the earlier time period, but none of the differences was significant. The authors point out, however, that the small number of patients treated under the final protocol resulted in limited statistical power.
Implications for Future Trials
“From the start to the end of the trial, there was substantial change to the protocol, which reflects the substantial change that had occurred in the approach to stroke patients with severe symptoms and a large brain artery blockage/occlusion,” M. Shazam Hussain, MD, of the Cleveland Clinic (Cleveland, OH), told TCTMD in an email.
One of the major shifts was the drop in the proportion of patients who received intraarterial t-PA alone as endovascular therapy, mostly attributed to the introduction of the Penumbra aspiration system (Penumbra) during protocol 4 and the Solitaire FR stent retriever (eV3) during the final protocol, the authors say.
In addition, the trial had a goal—which was successful—of shortening the time to treatment. “IMS III demonstrates that attempts to minimize the time to endovascular therapy are achievable and may increase the possibility of positive outcomes in ongoing and future endovascular trials,” Dr. Broderick and colleagues write.
“Examining changes in baseline variables, processes, and outcomes in relationship to changes in the protocol and practice is informative for the conduct and potential success of ongoing trials,” they add.
Dr. Hussain
concluded: “The good news here is that by the last protocol change, the
trial did mirror modern practice, allowing use of new (and better) technology
[and] emphasizing use of CT angiography (to confirm that a large brain artery
was blocked before taking the patient to an invasive procedure). Time to
treatment was also better over the course of the trial, and the emphasis in
current trials and clinical practice is to reduce the time to treatment as much
as possible.”
Source:
Broderick JP, Palesch YY, Demchuk
AM, et al. Evolution of practice during the Interventional Management of Stroke
III trial and implications for ongoing trials. Stroke. 2014;Epub ahead of print.
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Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …
Read Full BioDisclosures
- IMS III was supported by grants from the NIH and the National Institute of Neurological Disorders and Stroke. Study medication for intraarterial t-PA was supplied by Genentech. Catheters were supplied during early years of the trial by EKOS, Concentric Medical, and Cordis Neurovascular. Boehringer Ingelheim supplied support for investigator meetings in Europe.
- Dr. Broderick reports Genentech giving research money to his department for the PRISMS trial and Boehringer Ingelheim paying for his travel to an Australian stroke conference.
- Dr. Hussain reports being the local principal investigator for the SWIFT PRIME trial and serving on the board of the Society of NeuroInterventional Surgery.
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