Review of the ENCHANTED Trial (Enhanced Control of Hypertension and Thrombolysis Stroke Study)
How Low Can We Go With Intravenous Tissue-Type Plasminogen Activator Dose and Blood Pressure Level?
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ENCHANTED (Enhanced Control of Hypertensionn and Thrombolysis Stroke Study) was a 2-by-2 quasi-factorial, open-label, noninferiority trial assigning randomly 3310 thrombolysis-eligible patients to low-dose intravenous alteplase (0.6 mg/kg body weight) or to standard dose (0.9 mg per kilogram of body weight). The reported arm of the trial also included 935 patients who were randomly assigned to intensive or guideline-recommended blood pressure management.1 The investigators pointed out that surprisingly little research on the optimal dose of alteplase was conducted compared with cardiovascular studies using thrombolytic therapy and that the standard dose for the NINDS trial (National Institute of Neurological Disorders and Stroke) was chosen on the basis of small pilot dose-escalation studies.2 Furthermore, the Japanese drug authority has approved the lower dose based on an uncontrolled open-label study showing equivalent outcomes and lower frequency of intracerebral hemorrhagic complications compared with the standard dose. Other Asian registry studies showed inconsistent results. However, it would seem that one important aspect driving the idea of the lower dose was affordability of the treatment, and the investigators stated that low-dose alteplase has become a low-cost and possibly safer option for patients who cannot afford the standard dose or are elderly.3
The primary objective of the ENCHANTED trial was to show noninferiority of the low dose compared with the standard one (3-month disability or death, modified Rankin scale score of 2–6). In contrast to equivalence or superiority trials, the noninferiority trials try to show that the tested treatment is not …