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研究生:張月眉
研究生(外文):Yue-Mei Chang
論文名稱:比較Esomeprazole與Omeprazole對逆流性食道炎症狀緩解之隨機性臨床試驗
論文名稱(外文):Clinical Comparison Between Esomeprazole And Omeprazole For The Symptom Resolution In Patients With Refluxive Esophagitis: A Randomized Trial
指導教授:高雅慧高雅慧引用關係許博翔許博翔引用關係
指導教授(外文):Yea-Huei KaoBor-Shyang Sheu
學位類別:碩士
校院名稱:國立成功大學
系所名稱:臨床藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:113
中文關鍵詞:逆流性食道炎氫離子幫浦抑制劑
外文關鍵詞:Reflux esophagitis (RE)Proton pump inhibitors (PPI)EsomeprazoleOmeprazoleOn-demand therapy
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[研究背景] 逆流性食道炎(refluxive esophagitis, RE)在胃腸科門診中是日益常見疾病之一。臨床上使用氫離子幫浦抑制劑(proton pump inhibitor, PPI)其強力抑制胃酸的分泌,對逆流性食道炎的治療效益上,已成為最佳首選之藥物。其中omeprazole更為最原創之氫離子幫浦抑制劑,醫學文獻上有關於omeprazole治療逆流性食道炎之正面報告相當多。但使用PPI治療的期間常須延長數週甚至於長達6個月以上之久才足以避免復發(relapse)。理想上,祈能降低使用藥品量並達到成本效益之原則。Omeprazole之S-異構物(S-isomer) esomeprazole,是首次被研發的PPI光學異構物,經多篇文獻證實esomeprazole確實是有較omeprazole更為優異的藥物動力學及抑制胃酸的效果。本研究將探討病患接受esomeprazole治療是否比接受omeprazole能更早緩解逆流性食道炎之症狀。

[研究目的] 本研究主要目的是比較在1~8週內esomeparazole 40 mg緩解逆流性食道炎之症狀是否異於omeprazole 20 mg;次要目的是當
病患在第4週已達到症狀完全緩解時,施行“需要時才給藥”(on-demand)之治療方式來評估esomeparazole與omeprazole之療效。

[研究方法] 納入69位具有心頭灼熱感、胃酸逆流症狀之病患,其逆流食道炎經內視鏡檢查為洛杉磯分類系統A~D級,隨機再分成兩組各別接受一天一次omeprazole 20 mg (O20)或esomeprazole 40 mg (E40)共8 週。在治療前及第1週、第4週、第8週結束回診時,病患須接受逆流性食道炎症狀之嚴重度問卷,亦須繳回病患每日自我簡記症狀之記錄卡。自病患進入第5週起,依其第4週之症狀若已達完全緩解,將施行“需要時才給藥”(on-demand)之治療方式,直到第8週結束時回診,計算esomeprazole、omeprazole剩餘之藥品數量。

[研究結果] 第4週結束時E40組達到完全無心頭灼熱感及胃酸逆流症狀之病患百分比稍高於O20組( 71% vs. 55%,p = 0.189)。兩組達到無逆流性食道炎症狀之中位數(天)是相似的。E40組比O20組有更多病患能進入on-demand治療方式(ITT:44.4% vs. 18.5%,p = 0.04)。在接受on-demand治療患者中,E40組其剩餘藥品數量與O20組比較下是差不多。

[結論] Esomeprazole 40 mg比omeprazole 20 mg有較高百分比的患者能進入on-demand治療,亦可作為對逆流性食道炎患者施行on-demand之藥物。
Background: Refluxive esophagitis (RE) is growing one of the common diseases in gastroenterological clinic. The effective acid control by proton pump inhibitor (PPI) attributed as the drug of the best choice for RE in clinical practice. PPI, such as initially omeprazole, has been well established to heal the majority of patients with refluxive esophagitis in medical journals. However, PPI should be maintained for more than six months to prevent relapse. Ideally, the utilization of PPI should be minimized in the drug dosage to fulfill a more cost-beneficial rule. Esomeparzole, the S-isomer of omeparzole, is the first PPI to be developed as an optical isomer and demonstrates significantly superior pharmacokinetics and more effective acid control than omeprazole. The study will evaluate that the patients received esomeprazole can have an earlier remissive symptoms of RE than those treated with omeprazole.

Aims: The primary efficacy endpoint of the study is whether esomeprazole 40 mg is different from omeprazole 20 mg in improving symptoms of RE within 1~8 weeks. The secondary efficacy endpoint is to assess the efficacy of “on-demand” therapy when RE symptoms were totally free on the 4th week.

Methods: Sixty-nine patients with acid regurgitation (AR) or heartburn sensation (HB) were enrolled. Endoscopic severity of RE was graded in each patient by Los-Angles classification (Grade A-D). These patients were randomized to receive either omeprazole 20mg (O20 group) or esomeprazole 40mg (E40 group) qd for 8 weeks. The scores of AR and HB of RE evaluated by a questionnaire were evaluated on the baseline, the end of the 1st week, 4th week, and 8th week respectively. The patients’ cards of self-records every day in AR and HB were also returned. Once the patients achieved free from AR and HB at week 4, “on-demand” therapy began at the 5th week. The remaining tablets of esomeprazole or omeprazole were calculated on the end of the 8th week.

Result: The patients in E40 group had a slightly higher symptom-free than those in O20 group on the end of 4th week (71% vs. 55%, p = 0.189), but the rate doesn’t have statistical significance. The median day to achieve free from RE symptoms was similar in both groups. More patients in E40 group than in O20 group could start with “on-demand” therapy (ITT: 44.4% vs. 18.5%, p = 0.04). In the patients receiving “on-demand” therapy, the remaining tablets were similar in both groups.

Summary: Esomeprazole 40mg is superior to omeprazole 20mg for the rate of the patients receiving “on-demand” therapy and can be promisingly used as “on-demand” drug for RE patients.
目錄
中文摘要 i
英文摘要 iv
表目錄 x
圖目錄 xi
縮寫 xiii
第壹章 研究背景 1
第貳章 文獻回顧
第一節 前言:胃食道逆流疾病之流行病學與臨床症狀表現 2
第二節 24小時內正常胃酸分泌量與胃內pH值之動態分佈 4
第三節 胃食道逆流疾病之致病機轉 6
第四節 胃食道逆流疾病之分類 9
第五節 胃食道逆流疾病之治療 10
壹、 生活飲食習慣的改變 11
貳、 藥物治療 12
參、 手術治療 16
第六節 氫離子幫浦抑制劑的化學特性 17
第七節 氫離子幫浦抑制劑的藥理作用機轉 20
第八節 Esomeprazole之介紹-
壹、 Esomeprazole藥物藥動學特性與其他氫離子幫浦抑制劑之比較 23
貳、 Esomeprazole治療胃食道逆流疾病之臨床試驗 31
參、 Esomeprazole於胃食道逆流疾病維持療法之應用 33
第九節 氫離子幫浦抑制劑安全性 35
第十節 氫離子幫浦抑制劑-藥物與藥物之交互作用 37
第十一節 成本效益(cost-effectiveness) 39
第十二節 Esomeprazole於台灣應用之展望 41
第參章 研究目的 42
第肆章 研究材料 42
第伍章 研究方法
第一節 研究設計 43
第二節 研究對象 43
第三節 治療方法 45
第四節 評估指標
壹、 療效評估指標 46
貳、 安全性評估指標 48
第節 統計方法 49
第陸章 研究結果
第一節 研究對象 50
第二節 藥物療效評估
壹、 第1 ~ 4週藥物治療之情形 55
貳、 第5 ~ 8週藥物治療之情形 60
參、 能進入on-demand與未能進入on-demand病患間的差異性 63
肆、 藥品需求數量及藥費之情形 64
伍、 病患每次回診問卷評估之情形 66
第三節 安全性評估 68
第柒章 討論
第一節 藥物療效 69
第二節 整體耐受性、安全性評估結語 77
第三節 未來研究 78
第捌章 結論 80
參考文獻 82
附錄一、 臨床藥事服務 87
附錄二、 個案報告書 93
附錄三、 臨床試驗說明及同意書 109
附錄四、 藥委會及人體試驗委員會同意臨床試驗證明書 112
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