Bactericidal/permeability-increasing protein [rBPI21] in patients with hemorrhage due to trauma:: Results of a multicenter phase II clinical trial

被引:47
作者
Demetriades, D
Smith, JS
Jacobson, LE
Moncure, M
Minei, J
Nelson, BJ
Scannon, PJ
机构
[1] Univ So Calif, Los Angeles Cty Med Ctr, Los Angeles, CA 90033 USA
[2] Hershey Med Ctr, Hershey, PA USA
[3] Indiana Univ, Wishard Trauma Ctr, Indianapolis, IN 46204 USA
[4] Cooper Hosp Univ Med Ctr, Camden, NJ 08103 USA
[5] Univ Texas, SW Med Ctr, Dallas, TX USA
[6] XOMA Corp, Berkeley, CA USA
关键词
recombinant bactericidal/permeability-increasing; protein (rBPI(21)); trauma; hemorrhage; infection; pneumonia; ARDS; organ failure;
D O I
10.1097/00005373-199904000-00018
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Background: Infection and organ failure are the most common causes of death or serious complication in trauma patients surviving initial resuscitation and operation, Of the many possible causes of these complications, bacterial translocation and release of harmful cytokines and oxygen free radicals may play an important role in the pathogenesis of the complications associated with traumatic hemorrhage. Recombinant human bactericidal/permeability-increasing protein (rBPI(21)) has antibacterial and antiendotoxin properties, reduces cytokine levels, and increases survival in animal models of hemorrhagic shock. The primary objective of this study was to evaluate the safety and efficacy of prophylactic rBPI(21) infusion in patients with hemorrhage due to trauma. 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 rBPI(21) (4 mg . kg(-1) . 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 rBPI(21) 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 rBPI(21) 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 rBPI(21) 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 rBPI(21) group (hazard ratio = 0.66; post hoc p = 0.03). The beneficial trends of rBPI(21) 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: rBPI(21) 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.
引用
收藏
页码:667 / 676
页数:10
相关论文
共 42 条
  • [1] Abrahamson SL, 1997, J BIOL CHEM, V272, P2149
  • [2] AGARWAL N, 1993, ARCH SURG-CHICAGO, V128, P171
  • [3] AMMONS WS, 1993, CIRC SHOCK, V41, P176
  • [4] PROTECTIVE EFFECTS OF AN N-TERMINAL FRAGMENT OF BACTERICIDAL PERMEABILITY-INCREASING PROTEIN IN RODENT MODELS OF GRAM-NEGATIVE SEPSIS - ROLE OF BACTERICIDAL PROPERTIES
    AMMONS, WS
    KOHN, FR
    KUNG, AHC
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1994, 170 (06) : 1473 - 1482
  • [5] AMMONS WS, 1996, NOVEL THERAPEUTIC ST, P55
  • [6] [Anonymous], 1992, INFLAMMATION BASIC P
  • [7] Recombinant N-terminal fragment of bactericidal permeability increasing protein (rBPI(21)) prevents shock-induced microcirculatory alterations in the liver
    Bauer, C
    RiemerPaxian, I
    Larsen, R
    Marzi, I
    [J]. CRITICAL CARE MEDICINE, 1997, 25 (08) : 1283 - 1288
  • [8] Betz Corradin Sally, 1994, Journal of Infectious Diseases, V169, P105
  • [9] IMMEDIATE VERSUS DELAYED FLUID RESUSCITATION FOR HYPOTENSIVE PATIENTS WITH PENETRATING TORSO INJURIES
    BICKELL, WH
    WALL, MJ
    PEPE, PE
    MARTIN, RR
    GINGER, VF
    ALLEN, MK
    MATTOX, KL
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1994, 331 (17) : 1105 - 1109
  • [10] LETS AGREE ON TERMINOLOGY - DEFINITIONS OF SEPSIS
    BONE, RC
    [J]. CRITICAL CARE MEDICINE, 1991, 19 (07) : 973 - 976