Literature

NASCIS 1

Background Information

• National Acute Spinal Cord Injury Study (NASCIS) 1 was a randomized controlled trial conducted in the 1980s.
  • The study aimed to investigate the efficacy and safety of high-dose methylprednisolone in the treatment of acute spinal cord injury.

Study Design

• 306 patients from 9 hospitals were enrolled in NASCIS 1 from 1979 to 1981.
• One treatment group received a bolus of 1000 mg of MP followed by 250 mg every 6 hours for 10 days, and the other received a bolus of 100 mg followed by 25 mg every 6 hours for 10 days.
• The outcomes were measures of motor function, pinprick sensation, and light touch sensation.

Results

Conclusions

• NASCIS 1 did not provide conclusive evidence for the efficacy of high-dose methylprednisolone in the treatment of acute spinal cord injury.
• However, the study provided important insights into the dosing requirements for methylprednisolone treatment and highlighted the need for further research in this area.
• Subsequent trials, such as NASCIS 2 and 3, provided further evidence for the potential benefits of methylprednisolone treatment in acute spinal cord injury.

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NASCIS 2

Introduction

• NASCIS 2 trial tested the efficacy of methylprednisolone (MP) in acute SCI treatment
• Patients were randomized to MP, naloxone, or placebo groups
• Motor and sensory function were evaluated at 6 weeks, 6 months, and 1 year

Study Design

• 487 patients from 10 medical centers across 8 states were enrolled from 1985 to 1988
• Patients were randomized to:
  • MP 30 mg/kg then 5.4 mg/kg per hour x 23 h
  • Naloxone 5.4 mg/kg then 4 mg/kg per hour x 23 h
  • Placebo
• Motor function was evaluated on a 70-point scale, and sensory function on an 87-point scale
• Patients were evaluated at 6 weeks, 6 months, and 1 year Talking points:

Results

Conclusions

• MP is beneficial in acute SCI treatment, but only when started within 8 hours of injury
• Higher MP doses used in the trial targeted steroid effects that would not be mediated through glucocorticoid receptors
• Initiating MP more than 8 hours after injury was considered too late to see any impact from inhibition of lipid peroxidation
• Steroids may interfere with neuron regeneration, which could negatively impact patients starting treatment more than 8 hours after injury

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NASCIS 3

Background Information

• NASCIS 3 was a randomized controlled trial conducted in the 1990s.
• The study aimed to compare the effectiveness of a 24-hour versus 48-hour infusion of methylprednisolone (MP) and tirilazad mesylate in the treatment of acute spinal cord injury.
• A total of 499 patients were enrolled from 16 hospitals from 1991 to 1995.
• Outcome measures included neurologic examination and the Functional Independence Measure (FIM).

Study Design

• Patients were randomized to 3 groups: 20-40 mg/kg then either a 24-hour MP 5.4 mg/kg/hr infusion or a 48-hour MP 5.4 mg/kg/hr infusion, or tirilazad mesylate 2.5 mg/kg every 6 hours.
• Patients were stratified based on the time from injury to treatment: within 3 hours or between 3 and 8 hours.
• Outcome measures included neurologic examination and the Functional Independence Measure (FIM).
• Patients were assessed at 6 weeks, 6 months, and 1 year post-treatment.

Results

Conclusions

• Patients starting treatment within 3 hours of injury should be treated with the 24-hour infusion.
• Patients starting treatment between 3 and 8 hours after injury should be treated with a 48-hour infusion.
• The use of tirilazad did not provide any significant benefits over the use of MP infusions.
• The NASCIS investigators concluded that MP infusions can be an effective treatment option for acute spinal cord injury.

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Trial	Population	Years of Study	Total Sample Size	Study Groups
NASCIS 1	Open and closed acute SCI within 48 h of injury	1979-1981	306	·MP 1000-mg bolus then 250 mg every 6 h × 10 d   ·MP 100-mg bolus then 25 mg every 6 h × 10 d
NASCIS 2	Predominantly closed acute SCI within 12 h of injury	1985-1988	487	MP 30 mg/kg then 5.4 mg/kg per hour × 23 h Naloxone 5.4 mg/kg then 4 mg/kg per hour × 23 h Placebo
NASCIS 3	Acute SCI within 8 h of injury	1991-1995	499	MP 20-40 mg/kg then MP 5.4 mg/kg per hour × 23 h MP 5.4 mg/kg per hour × 48 h Tirilazad 2.5 mg/kg every 6 h × 48 h