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    原作者: Wan-Tsu Wendy Chang, 文章來源: 《中華急診醫學雜志》編輯部 發布日期:2015-03-03

    Title: Is progesterone yet another disappointing neuroprotectant?
    Author 作者: Wan-Tsu Wendy Chang
    翻譯:鄭辛甜 校對:肖鋒

    Is progesterone yet another disappointing neuroprotectant?
    Traumatic brain injury (TBI) affects more than 1.7 million persons in the U.S. annually. The incidence of TBI is increasing globally, especially in developing countries. Despite improvement in trauma systems and critical care, the morbidity and mortality associated with severe TBI remain high.
    Progesterone has been shown in preclinical and phase 2 randomized clinical trials to have pluripotent neuroprotective properties and improve mortality in TBI.
    Two multicenter phase 3 trials were recently completed and published in the December 25th issue of the New England Journal of Medicine. However, their results were disappointing.
    • The Progesterone for the Treatment of Traumatic Brain Injury (PROTECT III) trial, funded by the NIH, looked at progesterone administered within 4 hours after injury in patients with moderate to severe TBI.
    • 由NIH資助的孕激素對創傷性腦損傷的治療(PROTECT III)試驗中,中度至重度顱腦損傷患者傷后4小時內給予孕激素。
    • The Study of a Neuroprotective Agent, Progesterone, in Severe Traumatic Brain Injury (SYNAPSE) trial, funded by BHR Pharma, looked at progesterone administered within 8 hours after injury in patients with severe TBI.
    • 由BHR制藥公司資助的神經保護劑孕激素在重癥創傷性腦損傷患者中的(SYNAPSE)試驗,研究重癥創傷性腦損傷患者傷后8小時內給予孕激素。
    Both studies used the Glasgow Outcome Scale (GOS) or Extended
    Glasgow Outcome Scale (GOS-E) at 6 months as their primary outcome. The GOS and GOS-E capture the degree of recovery from brain injury in terms of disability, stratified into levels by death, vegetative state, severe disability, moderate disability, and good recovery.

    Progesterone was not found to have any benefit in functional outcome at 6 months.
    Both of these studies were well designed and conducted. However, they were based on small effect sizes of the phase 2 trials. In addition, they had very favorable outcome rates in the placebo group, thereby making it hard to demonstrate a benefit by their sample sizes.
    There has been a long history of failed neuroprotectant trials likely due to the complex and variable injury mechanisms involved in TBI. The currently available outcome measures are also insensitive to the targeted mechanistic endpoints. More research is needed to understand not only potential therapies but also how to select appropriate patients for these therapies.

    Take Home Point: Progesterone does not have any clear benefit in TBI at this time.

    References 參考文獻:
    Wright DW, Yeatts SD, Silbergleit R, et al. Very early administration of progesterone for acute traumatic brain injury. N Engl J Med. 2014;371(26):2457-2466.
    Skolnick BE, Maas AI, Narayan RK, et al. A clinical trial of progesterone for severe traumatic brain injury. N Engl J Med. 2014;371(26):2467-2476.