Tenecteplase for stroke salvage therapy--extending the therapeutic window via CT based selection.

Alteplase, tissue type plasminogen activator,t-PA has been the gold standard for fibrinolytic therapy in acute ischaemic stroke, approved for use by FDA within 3 hours of symptom onset. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, with prolonged plasma half life and higher fibrin selectivity, has emerged as a promising alternative intravenous alteplase. This article reviews the efficacy and safety of 2 doses of tenecteplase with alteplase as revealed by the phase 2B trial and attempts to compare their relative merits. Out of the 2678 patients between 2008 and 2011 with clinical features of stroke, 75 patients, age > 18 years, were recruitedin this randomized and blinded trial after screening within 6 hours. Inclusion criteria were set at NIHSS score > 4 and modified Rankin scale of < 2. Other baseline characteristics of patients were as follows: mean age 70 ± 8.2 years, 51 % males, 61 % hypertensive, 25 % diabetics and 25 % of the patients were currently smokers. Those with contraindication to alteplase were excluded. Prior to being enrolled in the trials patients underwent CT imaging employing multi detector scanners (16 or 64 slice) and only those with intracranial occlusion in the anterior cerebral, middle cerebral or posterior cerebral artery were included in the study. CT criteria for selection were: a perfusion lesion 20 % greater than the infarct core and evidence of associated vessel occlusion on CT angiography. Patients were divided randomly into three subgroups to receive standard dose of alteplase (0.9 mg per kilogram, the first 10% administered as an initial bolus and the remainder over a 1-hour period, with a maximum dose of 90 mg) or to tenecteplase (0.1 mg per kilogram, administered as a single bolus, with a maximum dose of 10 mg; or 0.25 mg per kilogram, administered as a single bolus, with a maximum dose of 25 mg). Central block randomization was done in blocks of 15 which allowed blind review after every 15 patients. Perfusion-weighted magnetic resonance imaging was done to assess difference in re perfusion 24 hours after treatment. NIHSS scale was employed to establish change in clinical presentation and symptoms before and after treatment. Other useful indicators of therapy benefit like vessel recanalisation post 24 hours and variation in infarct size were duly noted. Modified Rankin scale was employed to assess recovery and was hence calculated at the start of the study and repeated 90 days post treatment. …