NASCIS III

NASCIS III Trial Summary

Objective

The NASCIS III (National Acute Spinal Cord Injury Study III) trial aimed to compare the efficacy of 24-hour and 48-hour administration of methylprednisolone, and 48-hour administration of tirilazad mesylate, in improving neurological recovery in patients with acute spinal cord injury.

Methods

• Design: Multicenter, double-blind, randomized controlled trial.
• Participants: 499 patients with acute spinal cord injury diagnosed within 8 hours of injury.
• Interventions:

* 24-hour methylprednisolone (30 mg/kg bolus followed by 5.4 mg/kg per hour for 24 hours)
* 48-hour methylprednisolone (30 mg/kg bolus followed by 5.4 mg/kg per hour for 48 hours)
* 48-hour tirilazad mesylate (2.5 mg/kg bolus every 6 hours for 48 hours)

• Outcome Measures: Motor function change and Functional Independence Measure (FIM) assessed at 6 weeks and 6 months post-injury.

Results

• Neurological Recovery:

 * Patients treated with 48-hour methylprednisolone showed improved motor recovery at 6 weeks (P=.09) and 6 months (P=.07) compared to the 24-hour methylprednisolone group.
 * The effect was significant for patients starting treatment 3 to 8 hours after injury (P=.04 at 6 weeks, P=.01 at 6 months).
 * No significant difference in recovery was observed for tirilazad compared to 24-hour methylprednisolone.

• Adverse Events:

 * The 48-hour methylprednisolone group had higher rates of severe sepsis and severe pneumonia compared to other groups, but no significant difference in mortality.

Conclusion

The NASCIS III trial demonstrated that extending methylprednisolone administration to 48 hours provides significant neurological benefits for patients treated 3 to 8 hours post-injury. Tirilazad did not show superior efficacy compared to 24-hour methylprednisolone.

Reference

Bracken MB, Shepard MJ, Holford TR, et al. Administration of Methylprednisolone for 24 or 48 Hours or Tirilazad Mesylate for 48 Hours in the Treatment of Acute Spinal Cord Injury. JAMA 1997;277:1597-1604.