Abstract | BACKGROUND: METHODS: This was a phase II, multicenter, randomized, double-blind, placebo-controlled trial. Patients who required at least 2 U of blood were randomized to receive rBPI21 (4 mg x kg(-1) x d(-1) for 2 consecutive days) or an equivalent volume of placebo by continuous infusion within 12 hours of injury. The primary efficacy end point was mortality or serious complication occurring during the first 15 days of the study. Safety was monitored clinically and by laboratory panels during the study period. RESULTS: A total of 401 patients were treated (202 in the rBPI21 group and 199 in the placebo group). The composite end point rate of mortality or serious complication through day 15 was 46% in the placebo group and 39% in the rBPI21 group (hazard ratio = 0.79; p = 0.13). Secondary analysis, which adjusted for age, mechanism of injury, Injury Severity Score (1990 version), and units of blood received before study drug infusion showed similar results (hazard ratio = 0.79; p = 0.14). The proportion of patients who developed at least one serious organ dysfunction was 22% in the placebo group and 16% in the rBPI21 group (hazard ratio = 0.71; p = 0.14). The proportion of patients who developed either pneumonia or acute respiratory distress syndrome was 32% in the placebo group and 22% in the rBPI21 group (hazard ratio = 0.66; post hocp = 0.03). The beneficial trends of rBPI21 were observed in both blunt and penetrating trauma and were generally observed across different age groups, Injury Severity Scores, and units of blood transfused. No treatment difference was observed in mortality or resource utilization in this phase II study. CONCLUSION: rBPI21 was well-tolerated and demonstrated a favorable trend in reducing the composite primary end point of mortality or serious complication through day 15, especially respiratory complications, in patients with hemorrhage due to trauma. A phase III study is currently in progress.
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Authors | D Demetriades, J S Smith, L E Jacobson, M Moncure, J Minei, B J Nelson, P J Scannon |
Journal | The Journal of trauma
(J Trauma)
Vol. 46
Issue 4
Pg. 667-76; discussion 676-7
(Apr 1999)
ISSN: 0022-5282 [Print] United States |
PMID | 10217232
(Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Membrane Proteins
- endotoxin binding proteins
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Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Drug Administration Schedule
- Female
- Glasgow Coma Scale
- Hemorrhage
(classification, drug therapy, etiology, mortality)
- Humans
- Infusions, Intravenous
- Male
- Membrane Proteins
(administration & dosage, adverse effects, therapeutic use)
- Middle Aged
- Respiratory Distress Syndrome
(etiology)
- Severity of Illness Index
- United States
- Wounds and Injuries
(complications)
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