SYNTHESIS Expansion: design of a nonprofit, pragmatic, randomized, controlled trial on the best fast-track endovascular treatment vs. standard intravenous alteplase for acute ischemic stroke

Authors


  • Conflicts of interest: None declared.

  • Funding: This study was funded by the Italian Agency of Drugs (AIFA # FARM6LN3KS). The trial receives Alteplase from Boehringer Ingelheim Italia, which is paid by AIFA for the use in the experimental arm and by the single participating hospitals for the use in the control arm. The catheters and devices used in the study are those present in the participating interventional radiologists' apparatus and are refunded by the Niguarda Ca' Granda Hospital (Milan, Italy) with the AIFA funding.

Alfonso Ciccone*, Stroke Unit, Department of Neurosciences, ‘Niguarda Ca' Granda’ Hospital, Piazza Ospedale Maggiore 3, 20164 Milano, Italy.
E-mail: alfonso.ciccone@ospedaleniguarda.it; Study website: http://www.synthesisexpansion.com

Abstract

Rationale Reperfusion in ischemic stroke can be pursued by either systemic intravenous thrombolysis or endovascular treatment. However, systemic intravenous thrombolysis with alteplase within 4·5 h of symptom onset in selected patients is the only medication of proven efficacy. No randomized-controlled trials have so far compared the two modalities. To explore this, after a pilot phase, we started the SYNTHESIS Expansion trial.

Aims To determine whether endovascular treatment (i.e., intra-arterial thrombolysis with alteplase – if necessary, associated to or substituted by mechanical clot disruption and/or retrieval) compared with systemic intravenous thrombolysis with alteplase, administered according to European labelling, increases the proportion of independent survivors at three-months.

Design SYNTHESIS Expansion is an open-label, multicenter randomized-controlled trial, with blinded follow-up.

Eligibility applies to; patients with symptomatic ischemic stroke, seen within 4·5 h of onset; being able to initiate intravenous alteplase immediately, and endovascular treatment as soon as possible (not later than six-hours of stroke onset).

The study is pragmatically based on the ‘uncertainty principle’ between endovascular treatment and systemic intravenous thrombolysis for patients eligible for intravenous alteplase. There are no prespecified clinical or instrumental criteria to further select a patient, although investigators are left free to use them. Enrollment will be completed with 350 randomized patients. Primary analysis is on an intent-to-treat basis.

Study outcomes Primary: modified Rankin scale score of 0 or 1 at three-months. Secondary: neurological deficit seven-days after thrombolysis and the safety of the procedure on the basis of events reported within seven-days following thrombolysis – symptomatic cerebral hemorrhage, fatal and nonfatal stroke, death from any cause, neurological deterioration.

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