Young B, Runge J W, Waxman K S, Harrington T, Wilberger J, Muizelaar J P, Boddy A, Kupiec J W
Division of Neurosurgery, University of Kentucky College of Medicine, Lexington, USA.
JAMA. 1996 Aug 21;276(7):538-43.
To evaluate outcome of patients with severe closed head injury treated with pegorgotein, a scavenger of oxygen-derived free radicals.
Randomized, parallel, placebo-controlled, third-party-blind, multicenter trial, with a blinded, multicenter follow-up protocol.
Twenty-nine centers in the United States.
A total of 463 patients with severe closed head injury and a Glasgow Coma Scale score of 8 or less after resuscitation and stabilization.
Patients received a single intravenous dose of placebo, 10 000 U/kg of pegorgotein, or 20 000 U/kg of pegorgotein within 8 hours after injury.
The primary endpoint was the Glasgow Outcome Scale (GOS) score at 3 months after brain injury with GOS data trichotomized into good, fair, or poor outcome. Secondary efficacy endpoints included the Disability Rating Scale (DRS) and mortality. A secondary analysis was performed using GOS scores dichotomized into favorable and unfavorable outcomes. In a follow-up protocol at 6 months, GOS and DRS scores were again determined.
Of 463 patients randomized, 162 received placebo; 149, pegorgotein 10 000 U/kg; and 152, pegorgotein 20 000 U/kg. Treatment groups were comparable with respect to demographic characteristics, mechanism of injury, and time to treatment. Pegorgotein was well tolerated at both dose levels. At month 3, the trichotomized analysis found no significant statistical difference in neurologic outcome between the pegorgotein and the placebo groups. Although differences were not statistically significant, there were more favorable outcomes and no increase in the number of deaths or vegetative states among the patients given pegorgotein, more subjects had good or favorable outcomes with the 10 000-U/kg dose than with the 20 000-U/kg dose or placebo, and less disability was observed with the 10 000-U/kg dose than with either the 20 000-U/kg dose or placebo. No differences in mortality rate or cause of death were found between the 10 000-U/kg and placebo groups at either month 3 or month 6. The only statistically significant difference between the groups was a decreased incidence of adult respiratory distress syndrome in the 10 000-U/kg group as compared with the placebo group (P<.015).
In this clinical trial of 463 patients with severe head injury, no statistically significant difference in neurologic outcome or mortality was observed between patients treated with pegorgotein and those receiving placebo.
评估用氧自由基清除剂佩戈托汀治疗重度闭合性颅脑损伤患者的疗效。
随机、平行、安慰剂对照、第三方盲法、多中心试验，并采用盲法多中心随访方案。
美国29个中心。
共有463例重度闭合性颅脑损伤患者，复苏和病情稳定后格拉斯哥昏迷量表评分为8分或更低。
患者在受伤后8小时内接受单次静脉注射安慰剂、10000 U/kg佩戈托汀或20000 U/kg佩戈托汀。
主要终点是脑损伤后3个月时的格拉斯哥预后量表（GOS）评分，GOS数据分为良好、中等或不良预后。次要疗效终点包括残疾评定量表（DRS）和死亡率。采用将GOS评分分为有利和不利预后的方法进行二次分析。在6个月的随访方案中，再次测定GOS和DRS评分。
463例随机分组的患者中，162例接受安慰剂；149例接受10000 U/kg佩戈托汀；152例接受20000 U/kg佩戈托汀。治疗组在人口统计学特征、损伤机制和治疗时间方面具有可比性。两个剂量水平的佩戈托汀耐受性均良好。在3个月时，三分法分析发现佩戈托汀组和安慰剂组在神经学预后方面无显著统计学差异。虽然差异无统计学意义，但接受佩戈托汀治疗的患者中预后良好的更多，死亡或植物状态的数量没有增加，接受10000 U/kg剂量的患者比接受20000 U/kg剂量或安慰剂的患者有更多良好或有利的预后，并且接受10000 U/kg剂量的患者比接受20000 U/kg剂量或安慰剂的患者残疾程度更低。在3个月或6个月时，10000 U/kg组和安慰剂组之间的死亡率或死亡原因均无差异。两组之间唯一具有统计学意义的差异是10000 U/kg组与安慰剂组相比，成人呼吸窘迫综合征的发生率降低（P<0.015）。
在这项针对463例重度颅脑损伤患者的临床试验中，接受佩戈托汀治疗的患者与接受安慰剂治疗的患者在神经学预后或死亡率方面未观察到显著统计学差异。
