2011-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/656684摘要：【本計畫在去年曾提出三年期計畫，已先通過的第一年計畫現正在執行中（2010.8.1至2011.7.30），進行的情況很順利。這次我們除了繼續後兩年之schedule外，我們針對依計畫治療，而仍失敗的受試者，再規畫後續的處理及治療，以期最終能清除全部受試者的幽門螺旋桿菌感染。】幽門螺旋桿菌(幽菌)和一些重要上消化道疾病有強烈相關性。為期一週的三合一療法為目前清除幽菌的第一線用藥，但是由於抗藥性盛行率的增加，使得治療失敗率快速升高。第二線用藥的處方包括新抗生素的三合一療法、接續性療法及高劑量二合一療法等。十天期的接續療法被認為是不錯的救援療法，甚至也可用來做第一線治療。此外，含有levofloxacin的三合一療法也被用於一線治療失敗後的救援療法。基於化學穩定性，amoxicillin及一些抗生素在胃內pH值較高時，有較好的殺菌作用。多數質子幫浦抑制劑(PPI)主要經CYP2C19酵素代謝。研究顯示，把PPI使用劑量提高，可以減低CYP2C19基因型造成的衝擊。因此高劑量的二合一療法用於救援療法，其成功率可高於95%。由於amoxicillin之原發及次發抗藥性的盛行率仍然很低，因此高劑量的PPI/amoxicillin二合一療法應有潛力同時作為優良抗幽菌的第一線或救援治療。雖然目前文獻報告，給予一些較為可行的清除幽菌的第一線及第二線建議療法，但是在世界各地區，因為不同的人種代謝基因型，不同的抗藥性盛行率，不同的用藥服從性，常導致在不同地區有不同的療效，到底何者較佳，需要因地制宜。就我們所知，至目前為止鮮少有大規模前瞻性的研究同時比較這幾種被推薦療法的療效、副作用及服藥順從性等重要的資料，因此我們提出本計畫，目的包括：(1) 比較高劑量二合一療法、接續性療法、及含clarithromycin三合一療法作為第一線治療的療效；(2) 比較高劑量二合一療法、接續性療法、及含levofloxacin三合一療法作為救援治療的療效；(3) 比較服用這些療法的副作用及服藥順從性；(4) 探討可能影響這些療法的療效的因素；(5) 調查及分析最近三年抗生素抗藥性的變動情形。我們預估需要收集800例(第一線治療組及救援治療組各400例，組內療法至少各100例)才可達80% power。各組情形如下：1)第一線治療組分組：A1組 – high dose dual therapy (rabeprazole 20 mg/amoxicillin 750 mg qid 14天);B1組 – sequential therapy (rabeprazole 20 mg/amoxicillin 1000 mg, bid 5天, then rabeprazole 20 mg/metronidazole 500 mg/clarithromycin 500 mg, bid next 5天);C1組 – clarithromycin-based triple therapy (rabeprazole 20 mg/amoxicillin 1000 mg/clarithromycin 500 mg, bid 7天)。2) 救援治療組分組：A2組 – high dose dual therapy (同A1組);B2組 – sequential therapy (同B1組);C2組–levofloxacin-based triple therapy (rabeprazole 20 mg/amoxicillin 1000 mg/ levofloxacin 250 mg, bid 7天)。所有病患(年齡18歲以上)接受服藥前胃鏡評估及檢體收集，確認有慢性胃炎及/或消化性潰瘍合併有幽菌感染，服藥後以胃鏡取檢體或碳13呼氣試驗評估其療效。病患填寫一份問卷，同時在治療期間，每天記錄臨床症狀和藥物用量。自2010年8月開始至12月，我們已篩檢了250位病例，其中75位收錄進入第一線治療組，25位進入救援治療組，130位確定不符合納入/排除條件，另有20位仍在評估中。我們預估分別有50位於第一線治療和90位於救援治療之病例可能治療失敗。治療失敗很容易引起次發抗藥性，但amoxicillin則是較不易引起此種抗藥情況。針對這些病例，我們鼓勵他們接受胃鏡複檢，並做細菌培養，以觀察次發抗藥性的比例，並藉此選擇後續治療藥方。對於未做胃鏡複檢，及未有次發amoxicillin抗藥性的病例，我們將嘗試再使用高劑量二合一療法來治療，同時觀察此療法重覆使用的累積清除率。<br> Abstract: 【This project has been proposed for a 3-year period study last year, and has got a grant from NSC for the 1st year. It is now undergoing the 1st year’s schedule smoothly. This time, we will continue the schedule in the next years. Besides, we propose some additional targets that we want to investigate. Through these plans, we hope to eradicate Helicobacter pylori infection in all of the study cases.】H. pylori infection is associated with many gastrointestinal disorders. Although U.S. and European authorities endorse a 1-week triple therapy as first-line treatment for H. pylori infection, the rate of treatment failure has rapidly increased. Second-line therapies, including alternative triple therapy (TT), sequential therapy (ST) and high dose dual therapy (HDDT) have been recommended. A 10-day ST was proposed to be a promising rescue regimen for H. pylori treatment even as a 1st-line regimen. Levofloxacin-based TT has also been used as a salvage regimen. For chemical stability reasons, the antibacterial activity of amoxicillin, is better at a higher intragastric pH. Most PPIs are mainly metabolized by CYP2C19, however, the impact of CYP2C19 genotypes becomes less significant when PPI doses were increased. Thus, HDDT can achieve high eradication rates (>95%) as a rescue regimen. The amoxicillin-based dual therapy, with a very rare prevalence of primary and secondary antibiotic resistance, has the potential to be an optimal first-line and rescue anti-Helicobacter pylori regimen. This study aims: 1) to compare the efficacy of HDDT, ST and clarithromycin-based TT as 1st-line regimen in H. pylori eradication; 2) to compare the efficacy of HDDT, ST and levofloxacin-based TT as rescue regimen in H. pylori eradication; 3) to compare the patient adherence and adverse effects of these treatment regimens; 4) to investigate factors that may influence H. pylori eradication by these treatment regimens; and 5) the prevalence and trend of antibiotic resistance.Totally, we should enroll about 800 cases, 400 cases in each part (1st-line regimen or rescue regimen) of study. Each patient will be randomly allocated to 1) 1st-line regimens: group A1–HDDT (rabeprazole 20 mg/amoxicillin 750 mg qid for 14 days); group B1–ST (rabeprazole/amoxicillin 1000 mg, bid for 5 days, then rabeprazole/metronidazole 500 mg/clarithromycin 500 mg, bid for next 5 days); group C1–clarithromycin-based TT (rabeprazole/amoxicillin 1000 mg/clarithromycin 500 mg, bid for 7 days). 2) rescue regimens: group A2–HDDT (as group A1); group B2–ST (as group B1); group C2–levofloxacin-based TT (rabeprazole/amoxicillin 1000 mg/levofloxacin 250 mg, bid for 7 days). Patients, aged  18, having H. pylori-positive chronic gastritis with/without peptic ulcers will be recruited. All undergo endoscopy with biopsy before treatment. Four to eight weeks after termination of treatment, H. pylori infection status will be examined by endoscopy with biopsy or the 13C-urea breath test if the patients refuse the second endoscopy. All patients will be asked to complete a questionnaire and to record symptoms and drug consumption daily during the treatment period. Post-treatment, the patients were seen at the Outpatients Clinic to investigate patient adherence and adverse effects of treatment.From Aug to Dec 2010, we have screened 250 patients, 75 cases and 25 cases have been enrolled into the 1st-line regimen groups and rescue regimen groups, respectively. We will encourage the patient having treatment failure (about 50 cases in 1st-line regimen group and 90 cases in rescue regimen group) to receive repeated endoscopy with bacterial culture and drug susceptibility test. By this procedure we can choose the subsequent optimal regimen. For the patients without repeated endoscopy or without carrying acquired amoxicillin resistant strain, HDDT will be given again to evaluate the efficacy of this regimen used repeatedly and the cumulative eradication rateMacrophagesphenotypepolarizationmicroRNAsdifferential expressionmicroarrayinflammationnon-small cell lung cancers