Abstract
Introduction: In acute ischemic stroke, delayed revascularisation increases the risk of enlargement of the ischemic core associated with poor clinical outcome. Neuroprotective agents may immediately protect the penumbra and by that extend the time window for tissue-saving reperfusion. The vasoactive agent theophylline has been shown to reduce brain tissue edema, brain damage and mortality in animal stroke models. However, results from the animal studies, clinical case series and previous randomized clinical trials with theophylline in stroke patients were controversial. In this prospective trial, the primary study objective was to evaluate whether theophylline is safe and efficient in acute ischemic stroke patients as an add-on to thrombolytic therapy. Hypothesis: We hypothesized that treatment with theophylline can improve capillary flow in acute ischemic brain tissue and thus facilitate reperfusion leading to reduced volume of infarct growth and clinical improvement. Methods: The TEA-Stroke Trial is a two-center, proof of concept phase II clinical study with a randomized, double-blinded, placebo-controlled design. Patients with acute ischemic stroke verified by magnetic resonance imaging (MRI) and a National Institute of Health Stroke Scale ≥4 were randomized 1:1 to either theophylline or placebo as an add-on to standard thrombolytic therapy. The dual primary outcome measures included infarct growth assessed by MRI and clinical improvement assessed by the National Institute of Health Stroke scale at the 24-hour follow-up. A sample size of 120 subjects was estimated to detect a 22% difference between the treatment groups (80% power, alpha = 0.05) based on the MRI surrogate marker. Results: The study was stopped early after randomization of 64 patients for futility reasons because of slow recruitment. There were no safety concerns. Detailed blinded data analysis is ongoing and the main results will be presented. Conclusion: The TEA-Stroke Trial is the first study to evaluate whether the addition of theophylline to thrombolytic therapy is safe and efficient in patients with acute ischemic stroke. The main trial results will be discussed. Trial Registration: EudraCT number 2013-001989-42
Published Version
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