Abstract | OBJECTIVE: 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: INTERVENTIONS: 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:
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Authors | Bernhardt G Zeiher, Antonio Artigas, Jean-Louis Vincent, Alexei Dmitrienko, Kimberley Jackson, B Taylor Thompson, Gordon Bernard, STRIVE Study Group |
Journal | Critical care medicine
(Crit Care Med)
Vol. 32
Issue 8
Pg. 1695-702
(Aug 2004)
ISSN: 0090-3493 [Print] United States |
PMID | 15286546
(Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial)
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Chemical References |
- Serine Proteinase Inhibitors
- Sulfonamides
- sivelestat
- Leukocyte Elastase
- Glycine
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Topics |
- Australia
(epidemiology)
- Belgium
(epidemiology)
- Canada
(epidemiology)
- Double-Blind Method
- Female
- Follow-Up Studies
- Glycine
(administration & dosage, adverse effects, analogs & derivatives)
- Guideline Adherence
(statistics & numerical data)
- Humans
- Infusions, Intravenous
- Leukocyte Elastase
(antagonists & inhibitors, blood)
- Male
- Middle Aged
- New Zealand
(epidemiology)
- Outcome and Process Assessment, Health Care
- Prospective Studies
- Respiration, Artificial
(statistics & numerical data)
- Respiratory Distress Syndrome
(drug therapy, mortality)
- Serine Proteinase Inhibitors
(administration & dosage)
- Spain
(epidemiology)
- Sulfonamides
(administration & dosage, adverse effects)
- Survival Analysis
- Tidal Volume
- Time
- Treatment Outcome
- United States
(epidemiology)
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