Phase IIB Study of TNK in Acute Stroke (TNK-S2B-STAT)

TNK-S2B STAT and TNK-S2B CLIN are separate but highly coordinated units which together propose a large, multi-center, randomized controlled trial comparing TNK to rt-PA in patients with acute ischemic stroke treated within 3 hours of onset. The goals of TNK-S2B STAT are: 1) to provide a statistical design which establishes whether, compared to rt-PA, TNK shows promise in reducing poor outcomes following acute ischemic stroke, while minimizing follow-up time and the number of patients required. 2) to conduct, efficiently integrate, and be responsible for all TNK-S2B data management operations. 3) to transmit to the Clinical Coordinating Center (CCC) in a timely fashion all of the data which the principal investigator of TNK-S2B needs to meet his responsibilities in terms of ensuring patient safety and directing all clinical operations. The statistical analysis plan incorporates several innovative features: 1) A sequential selection procedure identifies one of two doses of TNK (0.1 or 0.4 mg/kg) as superior for Major Neurological Improvement at 24 hours. 2) An initial randomized comparison to rt-PA assesses the selected TNK dose for promise or futility. The outcome is the modified Rankin scale at 3 months. 3) If TNK is promising rather than futile, a phase III trial will compare TNK with rt-PA, again with the modified Rankin scale at 3 months as outcome. 3)For efficiency, the 200 patients included in the initial TNK/rt-PA comparison will be included in the phase III trial (overall n = 1908 patients) if it proceeds.