Antiplatelet therapy vs. anticoagulation in cervical artery dissection: rationale and design of the Cervical Artery Dissection in Stroke Study (CADISS)

Abstract

Rationale: Cervical artery dissection is an important cause of stroke in the young. It can present with local symptoms or stroke/transient ischaemic attacks. Following presentation there is a risk of stroke, particularly in the first month following presentation. The mechanism of stroke is believed to be thromboembolic in the majority of cases. Many clinicians anticoagulate patients with cervical dissection for 3-6 months. This is not evidence based and is supported by a paucity of data and no data from randomised control trials.

Aims: CADISS is a prospective multicentre randomised-controlled trial in acute (within 7 days of onset) carotid and vertebral artery dissection. Intracerebral artery dissection is excluded.

Design: Patients are randomised to antiplatelet therapy (aspirin, dipyridamole or clopidogrel alone or in dual combination) or anticoagulation therapy [heparin followed by warfarin aiming for an International Normalised Ratio (INR) in the range 2-3] for at least 3 months. Treatment is open-label.

Study outcome: The primary end-point is ipsilateral stroke or death within 3 months from randomisation. Secondary end-points include any TIA or stroke, major bleeding and presence of residual stenosis at 3 months (>50%). All neuroimaging and serious adverse events will be adjudicated blinded to treatment. An initial feasibility phase of 250 subjects will allow us to determine whether *there are sufficient clinical end-points to provide the power to determine a treatment effect and *adequate numbers of patients can be recruited. The feasibility phase will be continued into a fully powered definitive treatment trial. Initial power calculations based on limited natural history data suggest a sample size of approximately 3000. Sample size calculations will be refined once the frequency of outcome events during the feasibility phase is known.