Tenecteplase–Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion

Among the ≈700 000 ischemic strokes per year in North America, most (≤70%) are minor and initially nondisabling presenting with transient or persistent minor stroke symptoms (transient ischemic attack or minor stroke). However, this seemingly mild presentation is misleading because the prognosis is not benign. Multiple studies have reported that among patients considered too mild for thrombolysis, up to one third are dead or disabled in short-term (90 days) follow-up. Thrombolytic treatment of minor ischemic stroke is controversial with much variation in practice. Most physicians Background and Purpose—Minor stroke and transient ischemic attack with an intracranial occlusion are associated with neurological deterioration and disability. Tenecteplase (TNK–tissue-type plasminogen activator) compared with alteplase is easier to administer, has a longer half-life, higher fibrin specificity, possibly a lower rate of intracranial hemorrhage, and may be an ideal thrombolytic agent in this population. Methods—TNK–Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion (TEMPO-1) was a multicenter, prospective, uncontrolled, TNK–tissue-type plasminogen activator dose-escalation, safety, and feasibility trial. Patients with a National Institutes of Health Stroke Scale ≤5 within 12 hours of symptom onset, intracranial arterial occlusion on computed tomographic angiography and absence of well-evolved infarction were eligible. Fifty patients were enrolled; 25 patients at a dose of 0.1 mg/kg, and 25 patients at 0.25 mg/kg. Primary outcome was the rate of drug-related serious adverse events. Secondary outcomes included recanalization and 90-day neurological outcome (modified Rankin Scale, 0–1). Results—Median baseline National Institutes of Health Stroke Scale was 2.5 (interquartile range, 1), and median age was 71 (interquartile range, 22) years. There were no drug-related serious adverse events in tier 1. In tier 2, there was 1 symptomatic intracranial hemorrhage (4%; 95% confidence interval, 0.01–20.0). Stroke progression occurred in 6% of cases. Overall, 66% had excellent functional outcome (modified Rankin Scale, 0–1) at 90 days. Recanalization rates were high; 0.1 mg/kg (39% complete and 17% partial), 0.25 mg/kg (52% complete and 9% partial). Complete recanalization was significantly related to excellent functional outcome (modified Rankin Scale, 0–1) at 90 days (relative risk, 1.65; 95% confidence interval, 1.09–2.5; P=0.026). Conclusions—Administration of TNK–tissue-type plasminogen activator in minor stroke with intracranial occlusion is both feasible and safe. A larger randomized controlled trial is needed to prove that this treatment is efficacious. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01654445. (Stroke. 2015;46:00-00. DOI: 10.1161/STROKEAHA.114.008504.)