The Clomethiazole Acute Stroke Study in tissue-type plasminogen activator-treated stroke (CLASS-T) - Final results

Objective: To assess the safety of tissue-type plasminogen activator (t-PA) plus clomethiazole in patients with acute ischemic stroke and determine th e feasibility of combination stroke therapy. Background: Clomethiazole is a neuroprotectant that appeared to improve outcome in patients with clinical deficits of a major stroke (total anterior circulation syndrome [TACS]) in a previous study, the Clomethiazole Acute Stroke Study (CLASS). Combining a neuroprotectant such as clomethiazole with thrombolysis may augment the b eneficial effects of the two agents. CLASS-t-PA (CLASS-T) was a pilot study to explore the safety of the combination and the feasibility of performing combination treatment in the setting of acute ischemic stroke. Methods: In a randomized, double-blind design (stratified for age, severity at admissi on, and time since onset of stroke), all patients received 0.9 mg/kg t-PA b eginning within 3 hours of stroke onset and then either 68 mg/kg clomethiaz ole (n = 97) IV over 24 hours or placebo (n = 93) beginning within 12 hours of stroke onset. Patients were followed for 90 days. The main measures of safety were mortality and serious adverse events, and the main measure of f unctional outcome was the Barthel Index. Results: The number of serious adv erse event reports was 47 in the clomethiazole group and 48 in the placebo group. Death during the 90 days after treatment occurred in 15 clomethiazol e and nine placebo patients (p = 0.26). Sedation was reported as an adverse event during therapy in 42% of clomethiazole patients vs 13% of placebo pa tients. The proportion of patients with TACS was 53% in the clomethiazole g roup and 41% in the placebo group. In the TACS subgroup, 52.9% of the clome thiazole patients scored a Barthel Index greater than 60 vs 44.7% of placeb o patients (odds ratio 1.39; 95% CI 0.60 to 3.23). Conclusion: In this pilo t study, there were no safety concerns related to the combination of t-PA a nd clomethiazole. The combination paradigm proved feasible, although many p atients received clomethiazole several hours after thrombolysis; future stu dies must require prompt administration of the neuroprotectant either befor e or during administration of the thrombolytic. Patients with major strokes (TACS) may have the potential to benefit from the combination of t-PA and clomethiazole.