Efficacy and Safety of Riluzole in Acute Spinal Cord Injury: Rationale and Design of AOSpine Phase III Multicenter Double Blinded Randomized Controlled Trial
Bibliographic record
Abstract
Introduction There is convincing evidence from the preclinical realm that the pharmacologic agent riluzole attenuates certain aspects of the secondary injury cascade leading to diminished neurological tissue destruction in animal spinal cord injury (SCI) models. The safety and pharmacokinetic profile of riluzole has been studied in a multicenter pilot study in 36 patients. Efficacy of riluzole in acute human SCI has not been established. Material and Methods This phase II/III multicenter double-blind randomized controlled trial will involve up to 35 sites. A total of 351 patients with acute C4–C8 SCI and ASIA Impairment Grade A, B, or C will be randomized 1:1 to riluzole and placebo. Primary outcome is the change in ASIA Total Motor Score between baseline and 180 days. Other measures include ASIA Upper Extremity Motor Score; ASIA Lower Extremity Motor Score; ASIA Sensory Score; ASIA Grade; Spinal Cord Independence Measure; SF-36v2; EQ-5D, and GRASSP. The statistical design utilizes two-stage sequential adaptive trial. A sample size of 316 patients (158 in each arm) will have 90% power to detect 9 points difference in the ASIA Motor Score at one-sided α = 0.025. To account for losses to follow-up of up to 10%, the study will enroll 351 patients. Results Within the phase 1 study, a matched cohort analysis was performed comparing complication rates and neurological outcomes between patients who received riluzole and non-riluzole-treated patients from a prospective SCI registry. Although the groups experienced similar rates of complications, riluzole-treated cervical SCI patients experienced an additional 15.5 points in AMS recovery at 90 days after injury as compared with non-riluzole-treated patients. Although the phase I study was underpowered to investigate the efficacy, the current phase II/III study is poised to definitively address this question. Patient enrollment for this trial began on October 1, 2013. Conclusion This is a pivotal study of riluzole in acute SCI.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.088 | 0.052 |
| Meta-epidemiology (narrow) | 0.005 | 0.003 |
| Meta-epidemiology (broad) | 0.009 | 0.004 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.002 | 0.005 |
| Scholarly communication | 0.004 | 0.003 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.007 | 0.005 |
| Insufficient payload (model declined to judge) | 0.008 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".