Neutrophil elastase inhibition in acute lung injury: Results of the STRIVE study
Bibliographic record
Abstract
OBJECTIVE: Neutrophil elastase is believed to be an important mediator of acute lung injury. Sivelestat (ONO-5046, Elaspol) is a small molecular weight inhibitor of neutrophil elastase. The primary objectives of this study were to determine whether sivelestat would reduce 28-day all-cause mortality or increase the number of ventilator-free days (days alive and free from mechanical ventilation from day 1 to day 28) compared with placebo in mechanically ventilated patients with acute lung injury. DESIGN: Multiple-center, double-blind, placebo-controlled trial administering a continuous infusion of sivelestat at a dose of 0.16 mg.kg(-1)hr(-1). SETTING: One hundred and five institutions in the United States, Canada, Belgium, Spain, Australia, and New Zealand. PATIENTS: A total of 492 mechanically ventilated patients with acute lung injury. INTERVENTIONS: Patients were randomized in a 1:1 fashion to sivelestat or placebo. Study drug was administered as a continuous infusion for the duration of mechanical ventilation plus 24 hrs for a maximum of 14 days. All patients were managed using low tidal volume mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: The study was stopped prematurely at the recommendation of an external Data and Safety Monitoring Board, which noted a negative trend in long-term mortality rate. Final analysis revealed no effect of sivelestat on the primary end points of ventilator-free days (day 1-day 28) or 28-day all-cause mortality. There were 64 deaths in each treatment group within the 28-day study period, and the mean number of ventilator-free days was 11.4 and 11.9 in the sivelestat and placebo treatment groups, respectively (p =.536). There was no evidence of effect on measures of pulmonary function, including Pao2/Fio2, static lung compliance, and time to meeting weaning criteria. There was no difference in adverse events or serious adverse events between treatment groups. A comparison of the Kaplan-Meier 180-day survival curves showed no difference between treatment groups (p =.102), but there was an increase in 180-day all-cause mortality in the sivelestat treatment group compared with the placebo group (p =.006). CONCLUSIONS: Intravenous sivelestat had no effect on 28-day all-cause mortality or ventilator-free days in a heterogeneous acute lung injury patient population managed with low tidal volume mechanical ventilation.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
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".