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題 名 | 戰勝敗血症--活性蛋白質C的興亡史=Surviving Sepsis Campaign--The Rise and Fall of Activated Protein C |
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作 者 | 唐高駿; 陽光耀; | 書刊名 | 中華民國重症醫學雜誌 |
卷 期 | 13:1 2012.03[民101.03] |
頁 次 | 頁10-18 |
分類號 | 415.27 |
關鍵詞 | 敗血症; 活性蛋白C; 重症加護病房; 臨床試驗; Sepsis; Activated protein C; Intensive care unit; Clinical trial; |
語 文 | 中文(Chinese) |
中文摘要 | 敗血症起因於身體對感染產生過強之全身性免疫發炎反應;而伴有急性器官功能障礙的敗血症(嚴重敗血症)是重症加護病房病人死亡的最主要原因之ㄧ。現代的重症醫學研究,使我們知道充足的輸液治療,人工呼吸器的使用,人工器官及器官支持上之進步,能改善器官衰竭病患的死亡率。過去大劑量的類固醇、腫瘤壞死因子單株抗體等藥物都曾經在動物實驗中證明對敗血症有效,但是進一步的人體實驗卻無法證實其療效。 2001年新英格蘭醫學雜誌中發表的多國參與前瞻性研究: PROWESS 臨床試驗,發現基因工程技術合成的人體蛋白─活性蛋白 C(Activated Protein C, drotrecogin alfa)可以有效的降低嚴重敗血症患者 28天的死亡率。因此美國食物與藥品管理局 FDA於 2001年許可活性蛋白 C(Xigris, drotrecogin alfa)用於高死亡風險的嚴重敗血症患者, 2002 年歐洲藥物管理局 EMA及 2004年台灣的健保局也許可此藥物用於兩個以上器官衰竭之敗血症患者。雖然之後另有大型研究探討活性蛋白 C之療效,但是醫學文獻與重症醫療論壇仍對活性蛋白 C之角色有爭論,因此歐洲藥物管理局 2008年要求禮來公司再進行一個 PROWESSSHOCK臨床試驗。可惜本研究無法進一步顯示活性蛋白 C對敗血症之療效,禮來公司 2011年也決定將活性蛋白 C下市。本文將分析活性蛋白 C成功與失敗之原因,並探討戰勝敗血症活動對敗血症照護之影響。 |
英文摘要 | Sepsis is defined as a systemic inflammatory response syndrome resulting from the infection, and severe sepsis (a sepsis-induced acute organ dysfunction) is a major cause of death in the intensive care unit. From the advance of critical care medicine, we know that adequate fluid therapy, mechanical ventilation, and artificial organ support improve the outcomes of patients with severe sepsis. In the past, high-dose corticosteroid, anti-TNFα monoclonal antibody had been effective in the animal model of sepsis, but did not prove their efficacy in the phase III clinical trial. Surprisingly, PROWESS study published in the New English Journal of Medicine 2001 showed activated protein C reducing the 28-day mortality of severe sepsis significantly, and then FDA approved the indication of activated protein C “Xigris, drotrecogin alfa” in patients with high-mortality-risk sepsis. Thereafter, European Medicines Agency, (EMA) approved its indication in sepsis with multiple organ failure in 2002, and Bureau of National Health Insurance did the similar approval in 2004. However, there were still many debates and questions about the efficacy of Xigris in the medical literatures and conferences since its approval. In 2008, EMA requested Eli Lilly conduct a randomized control trial called “PROWESS SHOCK” to reconfirm the clinical efficacy of Xigris in septic shock. Unfortunately, PROWESS SHOCK study did not demonstrate the benefit of Xigris in septic shock, thus Eli Lilly decided to withdraw Xigris from the market in 2011. The rise and fall of Xigris in severe sepsis, as well as the impact of Surviving sepsis campaign are discussed in this review. |
本系統中英文摘要資訊取自各篇刊載內容。