NINDS tPA trial -secondary analysis based on 2 hour change in NIHSS

Abstract

The NINDS tPA stroke study was published in 1995. This medication remains the only FDA approved medication for the treatment of acute stroke. The use of this drug has remained controversial despite proven benefit; as outcomes (with respect to level of disability) were improved at 90 days. Benefit (in terms of improvement based on neurological exam) was not established in the short term as the primary outcome of part I of the study was a 4 point or more improvement in the National Institutes of Health Stroke Scale (NIHSS) at 24 hours. As there is significant biological plausibility that improvement at 24 hours is predictive of ultimate outcome it would be useful to develop a model that could predict with confidence the final degree of improvement based on changes within the first 24 hours; as this might allow for future acute stroke trials to be expedited.

The Dataset: A completely de-identified data set is available from the federal government with the data from all 624 patients enrolled in the trial. Of interest for this evaluation is the serial measurements of the NIHSS score (measured at baseline or prior to treatment, 2 hours, 24 hours and 90 days.) Data on level of disability at 90 days is also described using the modified Rankin Scale (mRS), which ranges from 0 (normal), 1 (no significant disability), 2 (some disability) to 6 (death). Results:Visually comparing the trend lines suggests that the majority of the separation between the tPA and control groups is occurring when comparing baseline to two hours. This makes biological sense as well; since re-canalization of an occluded artery would be likely to lead to such observed rapid improvement. Conclusions: Change in NIHSS at 2 hours is a potential useful tool in the design of future stroke trials.