Thrombolysis in Pediatric Stroke (TIPS)

Population-based studies have reported an annual incidence of childhood AIS ranging from 2.3 to 13 per 100,000 children. Ten percent of children die following AIS, and over 75% will suffer long-term neurological deficits. The morbidity from childhood AIS lasts many decades over a lifetime.

Published consensus-based guidelines for the treatment of acute childhood arterial ischemic stroke (AIS) all recommend against Tissue Plasminogen Activator (tPA) treatment due to the lack of safety and efficacy studies. The American Heart Association (AHA) guideline states: "Until there are additional published safety and efficacy data, tPA generally is not recommended for children with AIS outside a clinical trial (Class III, Level of Evidence C).

While the AHA recommendations leave open the option to consider tPA therapy in adolescents with AIS, there is an urgent need for age appropriate dosing and safety for tPA for children of all ages. The potential impact of finding an effective intervention such as tPA on the resulting financial and personal burden of stroke is enormous.

Thrombolysis in Pediatric Stroke (TIPS) is a five-year, international study designed to fill this urgent need. TIPS incorporates a multi-institutional, multi-disciplinary design to study the safety, dose finding and feasibility of intravenous (IV) tPA treatment in childhood AIS. The specific aims of the study include:

• Aim 1: Determine the maximal safe dose of IV tPA among three doses (0.75, 0.9, 1.0 mg/kg) among children in two independent arms, those aged 2-10 years and those aged 11-17 years within 4 ½ hours from onset of acute AIS.
• Aim 2: Measure the pharmacokinetics of tPA, including free tPA, PAI-1, and tPA antigen in children receiving IV tPA for acute AIS.

TIPS will further measure the 3-month neurological outcome in children treated with IV tPA.