Sachs Barton, Delacy Dawn, Green Jeffrey, Graham R Scott, Ramsay James, Kreisler Nevin, Kruse Peter, Khutoryansky Naum, Hu Serena S
Texas Back Institute Clinical Research Organization, Plano, TX, USA.
Spine (Phila Pa 1976). 2007 Oct 1;32(21):2285-93. doi: 10.1097/BRS.0b013e3181557d45.
Randomized, placebo-controlled, double-blind, multicenter, Phase IIa study.
To assess the safety and efficacy of recombinant-activated Factor VII (rFVIIa) in major spinal surgery.
Spinal fusion surgery can cause substantial blood loss and blood product transfusions. Recombinant FVIIa is approved for treatment of bleeding in patients with coagulation abnormalities and has been shown to reduce blood loss and transfusion requirements in surgery in patients with no underlying coagulopathy.
Forty-nine patients undergoing fusion of 3 or more vertebral segments were randomized and treated on losing 10% of their estimated blood volume (with total expected surgical blood loss > or = 20%) and received 3 doses (2-hour intervals) of placebo (n = 13) or 30, 60, or 120 microg/kg rFVIIa (n = 12 per group). The primary endpoint was safety. A priori-defined efficacy endpoints included blood loss and transfusion requirements between placebo and each rFVIIa dose group, adjusted for surgery duration, number of segments fused, and estimated blood volume.
Serious adverse events did not occur at any greater frequency in any of the treatment groups. One patient (3 x 30 microg/kg rFVIIa) with advanced cerebrovascular disease (undiagnosed, trial exclusion criterion) died 6 days after surgery due to an ischemic stroke. Mean blood loss was as follows: 2270 mL for placebo; 1909, 1262, and 1868 mL for 3 x 30, 3 x 60, and 3 x 120 microg/kg rFVIIa, respectively (differences not statistically significant). Mean adjusted surgical blood loss was as follows: 2536 mL for placebo; 1120, 400, and 823 mL for 3 x 30, 3 x 60, and 3 x 120 microg/kg rFVIIa, respectively (P < or = 0.001). Mean surgical transfusion volume was reduced by 27% to 50% with rFVIIa treatment (not significant). The mean adjusted surgical transfusion volume was reduced by 81% to 95% with rFVIIa treatment (P < or = 0.002).
No safety concerns were indicated for the use of rFVIIa in patients at all doses tested; rFVIIa reduced adjusted blood loss and adjusted transfusions during spinal surgery.
随机、安慰剂对照、双盲、多中心IIa期研究。
评估重组活化凝血因子VII（rFVIIa）在脊柱大手术中的安全性和有效性。
脊柱融合手术可导致大量失血及输血。重组凝血因子VIIa已被批准用于治疗凝血异常患者的出血，并且已证明可减少无潜在凝血病患者手术中的失血量和输血量需求。
49例接受3个或更多椎体节段融合手术的患者在预计失血量达10%（预计手术总失血量≥20%）时被随机分组并接受治疗，接受3剂（间隔2小时）安慰剂（n = 13）或30、60或120μg/kg rFVIIa（每组n = 12）。主要终点是安全性。预先定义的疗效终点包括安慰剂组与各rFVIIa剂量组之间的失血量和输血量需求，并根据手术持续时间、融合节段数和预计血容量进行调整。
任何治疗组中严重不良事件的发生频率均未更高。1例患有晚期脑血管疾病（未诊断，试验排除标准）的患者（3×30μg/kg rFVIIa组）术后6天因缺血性中风死亡。平均失血量如下：安慰剂组为2270 mL；3×30、3×60和3×120μg/kg rFVIIa组分别为1909、1262和1868 mL（差异无统计学意义）。平均调整后的手术失血量如下：安慰剂组为2536 mL；3×30、3×60和3×120μg/kg rFVIIa组分别为1120、400和823 mL（P≤0.001）。rFVIIa治疗使平均手术输血量减少了27%至50%（无统计学意义）。rFVIIa治疗使平均调整后的手术输血量减少了81%至95%（P≤0.002）。
在所有测试剂量下，rFVIIa用于患者均未显示出安全性问题；rFVIIa减少了脊柱手术中的调整后失血量和调整后输血量。
