TESPI (Thrombolysis in Elderly Stroke Patients in Italy): a randomized controlled trial of alteplase (rt-PA) versus standard treatment in acute ischaemic stroke in patients aged more than 80 years where thrombolysis is initiated within three hours after stroke onset.

Rationale: Intravenous (i.v.) thrombolysis with recombinant tissue-Plasminogen Activator (rt-PA) (alteplase) within three hours from symptom onset is the only approved treatment of pharmacological revascularization in acute ischaemic stroke. However, the current license limits the use of rt-PA to patients aged ≤80 years due to the lack of evidence of safety and efficacy of this treatment in the elderly from randomized clinical trials. This article describes the design of the Thrombolysis in Elderly Stroke Patients in Italy (TESPI) trial planned to fill the lack of controlled data on i.v. thrombolysis in this age category of stroke patients. Aims: To collect efficacy and safety data on i.v. alteplase (rt-PA) in patients aged more than 80 years, to demonstrate that the treatment of these patients within three hours of symptoms onset of an acute ischaemic stroke with i.v. rt-PA, compared to patients receiving standard treatment (according to the national guidelines), will result in an improved clinical outcome with a favourable benefit/risk ratio. Design: TESPI is a prospective, multicenter, national, open-label, controlled (non-treated group as control), randomized, parallel group trial with blinded evaluation of outcome in patients older than 80 years treated with i.v. rt-PA within three hours after ischaemic stroke onset. The randomization procedure assigns patients to the treatment group with IV alteplase (0·9mg/kg of body weight) or to standard treatment group with a 1:1 basis. A three-month follow-up, when applicable, is performed by a blind assessor. Six hundred patients will be enrolled (300 patients per arm) The study period has been planned to be of three years. Study Outcomes: The primary efficacy end-point is the disability at day 90, dichotomized as a favourable outcome (modified Rankin Scale 0-2) or unfavourable outcome (modified Rankin Scale 3-6). The main primary safety end-point is symptomatic intracerebral haemorrhage defined as any hemorrhage at the 22-36h post-treatment scan combined with neurological deterioration leading to an increase of one or more points at the National Institutes of Health Stroke Scale. The TESPI trial, with the protocol number FARM65KNKY, is registered in the European Union Drug Regulating Authorities Clinical Trials database with the number 2007-006177-88 and in the Stroke Trials Registry of the Washington University Internet Stroke Center.