European Stroke Treatment with Ancrod Trial - ESTAT


The goal of the trial was to evaluate treatment with ancrod, an agent derived from snake venom that defibrinates, compared with placebo among patients with acute ischemic stroke.

Study Design

Study Design:

Patients Enrolled: 1,222
Mean Follow Up: 12 months
Mean Patient Age: Mean age 68.5 years
Female: 40

Patient Populations:

Age >18 years; signs and symptoms of acute ischemic stroke in any vascular territory; symptoms lasting >30 minutes without significant improvement; treatment within 6 hours of recognized onset of symptoms; and SSS (excluding gait) <40 at baseline


Clinical or CT evidence of brain hemorrhage or hemorrhagic infarction; CT evidence of potentially progressive brain lesion or of developing infarction; very mild stroke; stroke known or suspected to be caused by an arterial dissection; coma; previous stroke within 6 weeks; deficit from transient ischemic attack within 6 hours of stroke onset; ipsilateral neurological deficit from previous stroke interfering with assessment; deficit attributed to migraine, hypoglycemia, or sequelae of recent seizure; recent or anticipated surgery; hypertension severe and uncontrolled hypotension; antihypertensive drug given <15 minutes before treatment; thrombolytic therapy taken within 1 week or anticipated; coagulation disorder; or baseline plasma fibrinogen ≤2.9 µmol/L

Primary Endpoints:

Functional success at 3 months, defined as survival to follow-up with a Barthel Index score of 95–100 or at least equal to the prestroke value

Secondary Endpoints:

Modified SSS, modified Rankin Scale, mortality at 3 and 12 months, and CT infarct volume data at 7 days

Drug/Procedures Used:

Prior to randomization, all patients underwent brain computed tomography (CT) scans to exclude those with intracranial hemorrhages (ICHs) and large evolving ischemic infarctions. Patients were then randomized in a double-blind manner to ancrod (n = 604) or placebo (n = 618). Investigators were not allowed to administer antiplatelet agents, oral anticoagulants, thrombolytics, heparin, or other drugs that work on the fibrinolytic system.

Principal Findings:

Baseline characteristics were well balanced between groups, with 87% of patients presenting within 3-6 hours of symptom onset, 12% having had a prior stroke, and a mean pretreatment SSS of 26.8.

There was no difference in the primary endpoint of functional outcome at 3 months (42% in both the ancrod group and the placebo group, p = NS). Increase in Scandinavian Stroke Scale (SSS) was lower in the ancrod group than in the placebo group (increase of 3.6 vs. 5.2, p = 0.042). Rankin Scale at 3 months did not differ between groups, with success in 46% of the ancrod group and in 48% of the placebo group (p = 0.58). Symptomatic ICH within 28 days occurred more frequently in the ancrod group (7.3% vs. 1.5%, p = 0.007), as did asymptomatic ICH (5% vs. 2%, p = 0.011). Mortality at 3 months was higher in the ancrod group (20% vs. 14%, p = 0.026), but there was no difference at 12 months (25% vs. 21%, p = 0.25).


Among patients with acute ischemic stroke, treatment with ancrod, an agent derived from snake venom that defibrinates, was not associated with a difference in the primary endpoint of functional outcome at 3 months compared with placebo, but was associated with an increased risk of ICH and an early mortality hazard.

Data from the present study differ from the earlier and smaller STAT trial, which showed improvements in functional outcomes with ancrod and no excess of mortality. However, there were several differences between the trials, including the inclusion of patients with symptom onset beyond 3 hours in the present study, but not in the STAT trial, as well as the strict screening and exclusion of patients with hemorrhage or hemorrhagic infarction.


Hennerici MG, Kay R, Bogousslavsky J, Lenzi GL, Verstraete M, Orgogozo JM. Intravenous ancrod for acute ischaemic stroke in the European Stroke Treatment with Ancrod Trial: a randomised controlled trial. Lancet 2006;368:1871-8.

Clinical Topics: Anticoagulation Management, Noninvasive Imaging, Computed Tomography, Nuclear Imaging

Keywords: Thrombolytic Therapy, Stroke, Infarction, Platelet Aggregation Inhibitors, Tomography, X-Ray Computed, Snake Venoms, Heparin, Fibrinolytic Agents, Intracranial Hemorrhages, Research Personnel, Gait

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