Prediction of the treatment benefit of intravenous alteplase treatment for acute ischemic stroke

Lead Investigator: Diederik Dippel, Erasmus MC University Medical Center
Title of Proposal Research: Prediction of the treatment benefit of intravenous alteplase treatment for acute ischemic stroke
Vivli Data Request: 8751
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Alteplase is the drug of choice for fibrinolytic treatment (an emergency treatment used to dissolve blood clots before they become fatal) of patients with acute ischemic stroke (AIS). AIS is characterized by the sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of functions associated with the nervous system. The effect of alteplase is time-dependent and outcome after stroke is affected by several prognostic factors such as stroke severity and age. Patients at risk of harm from alteplase should ideally be identified prior to treatment with alteplase. Modelling the effect of alteplase as a function of prognostic factors and credible treatment effect modifiers (i.e. time-to-treatment) is a reasonable approach to predict individualized treatment benefit of alteplase in patients with acute ischemic stroke. Several years ago, David Kent et al. developed two separate prediction models (Stroke-TPI) for treatment benefit of alteplase treatment in AIS.These models did not use the full modified Rankin Scale (mRS) (measures the degree of disability/dependence after a stroke and is widely applied for evaluating recovery from stroke, with a scale from 0 to 6) as outcome and collapsed the National Institutes of Health Stroke Scale (NIHSS) that represents stroke severity in three broad categories. NIHSS is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke and aid planning post-acute care. Furthermore, it did not use the data from IST-3, a large pragmatic open-label RCT of alteplase versus no alteplase in 3035 AIS patients.(IST-3 collaborative group et al., 2012) There is a need to develop a single updated prediction model with the full mRS as outcome and the full NIHSS scale for stroke severity, based on the available data of high-quality randomized clinical trials (RCT) for alteplase. Treatment benefit will be defined as the difference in probability of functional independence (mRS 0-2; 0-2 on the modified Rankins Scale represents a good outcome, with functional independence for the patient) between alteplase treatment and no treatment. Our present aim is to develop a model that could support physicians and patients in shared decision making for treatment with alteplase, by providing individualized estimates of treatment benefit. Results of this study will be submitted for publication in an international scientific journal.

Requested Studies:

ECASS III – European Cooperative Acute Stroke Study III: A Placebo Controlled Trial of Alteplase (Rt-PA) in Acute Ischemic Hemispheric Stroke Where Thrombolysis is Initiated Between 3 and 4 Hours 30 Minutes After Stroke Onset
Data Contributor: Boehringer Ingelheim
Study ID: NCT00153036
Sponsor ID: 135.312

A placebo controlled trial of alteplase (rt-PA) in acute ischemic hemispheric stroke where thrombolysis is initiated up to 6 hours following the onset of symptoms (ECASS-II)
Data Contributor: Boehringer Ingelheim
Study ID: 135.291
Sponsor ID: 135.291