Clinical trial NCT00161070: ESPRIT: European/Australasian Stroke Prevention in Reversible Ischaemia Trial
Official title: ESPRIT: European/Australasian Stroke Prevention in Reversible Ischaemia Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Brain Ischemia
Transient Ischemic Attack
Arteriosclerosis
Keywords: secondary prevention
TIA / minor stroke
atherosclerotic origin
TIA (Transient Ischemic Attack)
prevention & control
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
First posted: 2005-09-12
Enrollment: 4500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The objective of ESPRIT was to compare the efficacy and safety of mild anticoagulation or a combination treatment of aspirin and dipyridamole with the efficacy and safety of treatment with aspirin alone after cerebral ischemia of arterial origin.

Detailed description: Low-dose aspirin (ASA) (at least 30 mg/day) prevents only 13% of subsequent vascular events after minor cerebral ischemia of arterial origin. Anticoagulation (AC) has been proven highly effective in preventing vascular events after myocardial infarction and after cerebral ischemia in patients with atrial fibrillation. A previous study on the effects of AC after cerebral ischemia of arterial origin (SPIRIT) showed that high intensity AC (INR 3.0 to 4.5) is not safe, but that mild AC (INR 2.0 to 3.0) was. The 2nd European Stroke Prevention Trial (ESPS-2) reported a 22% relative risk reduction of the combination of ASA and dipyridamole (DIP) above that of ASA only; its results, however, are subject to debate.

Study design: ESPRIT was an open randomised controlled trial allocating patients who experienced a transient ischemic attack (TIA) or a non-disabling ischemic stroke to either:

A. oral AC (INR 2.0 to 3.0);

B. the combination of DIP (400 mg daily) plus ASA (30-325 mg/day); or

C. ASA only (same dose).

The mean follow-up was three years. Primary outcome was the composite of vascular death, stroke, myocardial infarction or major bleeding. Outcome assessment is blind.

Eligibility criteria: Inclusion Criteria:

* Patients presenting in the participating hospitals with a TIA or non-disabling stroke of atherosclerotic origin
* Randomisation within 6 months after the TIA or minor stroke
* Modified Rankin scale of 3 or less

Exclusion Criteria:

* (Contra)indication to, or intolerance to, anticoagulants, dipyridamole, or aspirin
* Disease expected to cause death within weeks or months
* Source of embolism in the heart
* Moderate or severe ischemic damage to the white matter of the brain (leukoaraiosis)
* Anemia, polycythemia, thrombocytosis, or thrombocytopenia
* Planned carotid endarterectomy
* Intracranial bleeding or cerebral tumour
* TIA or stroke caused by vasculitis, migraine, or dissection
* Severe hypertension
* Liver failure
* Pregnancy
* Chronic alcohol abuse

Primary outcomes:
measure: The combined event of death from all vascular causes, nonfatal stroke, nonfatal myocardial infarction or major bleeding complication, whichever happens first during follow-up
Secondary outcomes:
measure: Death from all causes
measure: death from vascular causes
measure: death from vascular causes or nonfatal stroke
measure: fatal or nonfatal stroke
measure: death from vascular causes, nonfatal stroke, nonfatal myocardial infarction or vascular intervention
measure: major bleeding complications
measure: amputations of lower extremities
measure: retinal infarction or bleeding
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: UMC Utrecht
name: A. Algra, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: UMC Utrecht
name: J. Gijn Van, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: ESPRIT Study Group; Halkes PH, van Gijn J, Kappelle LJ, Koudstaal PJ, Algra A. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet. 2006 May 20;367(9523):1665-73. doi: 10.1016/S0140-6736(06)68734-5.
citation: ESPRIT Study Group; Halkes PH, van Gijn J, Kappelle LJ, Koudstaal PJ, Algra A. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial. Lancet Neurol. 2007 Feb;6(2):115-24. doi: 10.1016/S1474-4422(06)70685-8.
citation: Narasimhalu K, Ang S, De Silva DA, Wong MC, Chang HM, Chia KS, Auchus AP, Chen CP. The prognostic effects of poststroke cognitive impairment no dementia and domain-specific cognitive impairments in nondisabled ischemic stroke patients. Stroke. 2011 Apr;42(4):883-8. doi: 10.1161/STROKEAHA.110.594671. Epub 2011 Feb 17.