Phase IIB/III trial of tenecteplase in acute ischemic stroke: results of a prematurely terminated randomized clinical trial.

BACKGROUND AND PURPOSE: Intravenous alteplase (rtPA) remains the only approved treatment for acute ischemic stroke, but its use remains limited. In a previous pilot dose-escalation study, intravenous tenecteplase showed promise as a potentially safer alternative. Therefore, a Phase IIB clinical trial was begun to (1) choose a best dose of tenecteplase to carry forward; and (2) to provide evidence for either promise or futility of further testing of tenecteplase versus rtPA. If promise was established, then the trial would continue as a Phase III efficacy trial comparing the selected tenecteplase dose to standard rtPA. METHODS: The trial began as a small, multicenter, randomized, double-blind, controlled clinical trial comparing 0.1, 0.25, and 0.4 mg/kg tenecteplase with standard 0.9 mg/kg rtPA in patients with acute stroke within 3 hours of onset. An adaptive sequential design used an early (24-hour) assessment of major neurological improvement balanced against occurrence of symptomatic intracranial hemorrhage to choose a "best" dose of tenecteplase to carry forward. Once a "best" dose was established, the trial was to continue until at least 100 pairs of the selected tenecteplase dose versus standard rtPA could be compared by 3-month outcome using the modified Rankin Scale in an interim analysis. Decision rules were devised to yield a clear recommendation to either stop for futility or to continue into Phase III. RESULTS: The trial was prematurely terminated for slow enrollment after only 112 patients had been randomized at 8 clinical centers between 2006 and 2008. The 0.4-mg/kg dose was discarded as inferior after only 73 patients were randomized, but the selection procedure was still unable to distinguish between 0.1 mg/kg and 0.25 mg/kg as a propitious dose at the time the trial was stopped. There were no statistically persuasive differences in 3-month outcomes between the remaining tenecteplase groups and rtPA. Symptomatic intracranial hemorrhage rates were highest in the discarded 0.4-mg/kg tenecteplase group and lowest (0 of 31) in the 0.1-mg/kg tenecteplase group. Neither promise nor futility could be established. CONCLUSION: This prematurely terminated trial has demonstrated the potential efficiency of a novel design in selecting a propitious dose for future study of a new thrombolytic agent for acute stroke. Given the truncation of the trial, no convincing conclusions can be made about the promise of future study of tenecteplase in acute stroke.

Tissue plasminogen activator for acute ischemic stroke: a New York city emergency medicine perspective.

Nationally, only 2-3% of patients with acute ischemic stroke (AIS) currently receive tissue plasminogen activator (TPA). To better understand the reasons, we investigated the practice patterns, level of familiarity and acceptance of TPA for AIS among emergency physicians in New York City (NYC). Fifty-seven 911-receiving hospital emergency department directors were surveyed regarding TPA use. Of those responding, 37% had never used TPA to treat AIS. Lack of neurological support was reported by 33%. Departments with formal protocols were more likely to use TPA for AIS. In conclusion, there is considerable variation in the practice, knowledge, and attitudes regarding the use of TPA for AIS in NYC emergency departments. Improved educational efforts and institutional support may be necessary to ensure the appropriate use of TPA by emergency physicians.

Not for industry only: medical students and office-based academic detailing the PIVOT (Pregnant women Influenza Vaccine Optimization Team) initiative.

Academic detailing is a method of educational outreach that utilizes individualized encounters with physicians to broach specific medical issues in an evidence-based and quality-driven manner. Medical students utilized the matter of influenza vaccination during pregnancy as a lens through which to explore the methods of academic detailing in a community setting. Structured and customized dialogues between North Shore-LIJ affiliated obstetricians and Hofstra North Shore-LIJ medical students were conducted regarding the disparity between the proportion of providers that recommend the vaccine and the percentage of pregnant women being vaccinated annually. Ultimately the project aimed to increase vaccine-carrying rates throughout office based practices in the community, while establishing a viable method for up-to-date information exchange between practicing physicians and academic medicine. While the extent of affected change is currently being quantified, the project proved successful insofar as academic detailing allowed the students to gain access to physicians, and engage in compelling and educational conversations. Both the physicians and students felt these interactions were valuable and well worth continuing. The goal for the future is to expand these practices to other pressing public health issues while continuing to refine the technique.