@article{ee0db678eba04ddf9a95271a40512833,
title = "Efficacies of Genotypic Resistance-Guided vs Empirical Therapy for Refractory Helicobacter pylori Infection",
abstract = "Background & Aims: We aimed to compare the efficacy of genotypic resistance–guided therapy vs empirical therapy for eradication of refractory Helicobacter pylori infection in randomized controlled trials. Methods: We performed 2 multicenter, open-label trials of patients with H pylori infection (20 years or older) failed by 2 or more previous treatment regimens, from October 2012 through September 2017 in Taiwan. The patients were randomly assigned to groups given genotypic resistance–guided therapy for 14 days (n = 21 in trial 1, n = 205 in trial 2) or empirical therapy according to medication history for 14 days (n = 20 in trial 1, n = 205 in trial 2). Patients received sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole, with levofloxacin, clarithromycin, or tetracycline (doxycycline in trial 1, tetracycline in trial 2) for another 7 days (all given twice daily) based on genotype markers of resistance determined from gastric biopsy specimens (group A) or empirical therapy according to medication history. Resistance-associated mutations in 23S ribosomal RNA or gyrase A were identified by polymerase chain reaction with direct sequencing. Eradication status was determined by 13C-urea breath test. The primary outcome was eradication rate. Results: H pylori infection was eradicated in 17 of 21 (81%) patients receiving genotype resistance–guided therapy and 12 of 20 (60%) patients receiving empirical therapy (P =.181) in trial 1. This trial was terminated ahead of schedule due to the low rate of eradication in patients given doxycycline sequential therapy (15 of 26 [57.7%]). In trial 2, H pylori infection was eradicated in 160 of 205 (78%) patients receiving genotype resistance–guided therapy and 148 of 205 (72.2%) patients receiving empirical therapy (P =.170), according to intent to treat analysis. The frequencies of adverse effects and compliance did not differ significantly between groups. Conclusions: Properly designed empirical therapy, based on medication history, is an acceptable alternative to genotypic resistance–guided therapy for eradication of refractory H pylori infection after consideration of accessibility, cost, and patient preference. ClinicalTrials.gov ID: NCT01725906.",
keywords = "23S rRNA, Gyrase A, Susceptibility Testing, Third-Line",
author = "{Taiwan Gastrointestinal Disease and Helicobacter Consortium} and Liou, {Jyh Ming} and Chen, {Po Yueh} and Luo, {Jiing Chyuan} and Lee, {Ji Yuh} and Chen, {Chieh Chang} and Fang, {Yu Jen} and Yang, {Tsung Hua} and Chang, {Chi Yang} and Bair, {Ming Jong} and Chen, {Mei Jyh} and Hsu, {Yao Chun} and Hsu, {Wen Feng} and Chang, {Chun Chao} and Lin, {Jaw Town} and Shun, {Chia Tung} and El-Omar, {Emad M.} and Wu, {Ming Shiang} and Liou, {Jyh Ming} and Lee, {Yi Chia} and Lin, {Jaw Town} and Wu, {Chun Ying} and Wu, {Jeng Yih} and Chen, {Ching Chow} and Lin, {Chun Hung} and Fang, {Yu Ren} and Bair, {Ming Jong} and Luo, {Jiing Chyuan} and Wu, {Ming Shiang} and Cheng, {Tsu Yao} and Tseng, {Ping Huei} and Chiu, {Han Mo} and Chang, {Chun Chao} and Yu, {Chien Chun} and Chiu, {Min Chin} and Chen, {Yen Nien} and Hu, {Wen Hao} and Chou, {Chu Kuang} and Tai, {Chi Ming} and Lee, {Ching Tai} and Wang, {Wen Lun} and Chang, {Wen Shiung}",
note = "Funding Information: Funding This study was funded by the Ministry of Science and Technology, Executive Yuan, ROC, Taiwan (grant number: 102-2628-B-002-034-MY3, 104-2325-B-002-002, 105-2325-B-002-042, TCTC-TR2 106-2321-B-002-025, and MOST 107-3017-F-002-002-), the Ministry of Health and Welfare of Taiwan (grant number: MOHW106-TDU-B-211-113002, MOHW107-TDU-B-211-123002), Center of Precision Medicine from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan (Grant Number: NTU- 107L9014-1), and the National Taiwan University Hospital (grant number: NTUH 104-P05, NTUH 106-P06). EM El-Omar is funded by grants from the Australian Federal Government to the St George and Sutherland Medical Research Foundation. The funding source had no role in study design, data collection, analysis or interpretation, report writing or the decision to submit this paper for publication. Funding Information: The authors would like to express their special thanks to the staff of the Eighth Core Lab, Department of Medical Research, National Taiwan University Hospital and the Taipei Institute of Pathology for their technological support. Taiwan Helicobacter Consortium investigators: Steering committee of The Taiwan Gastrointestinal Disease and Helicobacter Consortium: Jyh-Ming Liou (Taipei), Yi-Chia Lee (Taipei), Jaw-Town Lin (Taipei), Chun-Ying Wu (Taipei), Jeng-Yih Wu (Kaohsiung), Ching-Chow Chen (Taipei), Chun-Hung Lin (Taipei), Yu-Ren Fang (Yun-Lin), Ming-Jong Bair (Taitung), Jiing-Chyuan Luo (Taipei), and Ming-Shiang Wu (Taipei). Others investigators of the Taiwan Helicobacter Consortium in this study: Tsu-Yao Cheng (Taipei), Ping-Huei Tseng (Taipei), Han-Mo Chiu (Taipei), Chun-Chao Chang (Taipei), Chien-Chun Yu (Yun-Lin), Min-Chin Chiu (Yun-Lin),Yen-Nien Chen (Hsinchu), Wen-Hao Hu (Hsinchu), Chu-Kuang Chou (Chia-Yi), Chi-Ming Tai (Kaohsiung), Ching-Tai Lee (Kaohsiung), Wen-Lun Wang (Kaohsiung), and Wen-Shiung Chang (Taipei). Author contributions: The study was conceived by JM Liou, with input from two senior authors, EM El-Omar and MS Wu, and all the other listed contributors from the Taiwan Helicobacter Consortium. JM Liou designed the study and wrote the protocol. JM Liou and MS Wu applied for funding of this trial. JM Liou, PY Chen, JC Luo, JY Lee, YJ Fang, CC Chen, CY Chang, MJ Bair, MJ Chen, YC Hsu, TH Yang, WF Hsu, CH Tseng, YC Hsu, JY Lee, TH Yang, CC Chang, JT Lin, and MS Wu recruited patients to the study. CT Shun contributed to the histological assessment. JM Liou prepared the statistical analyses. WF Hsu performed the decision model analysis. JM Liou drafted the article, which was critically revised by MS Wu and EM El-Omar. All authors commented on drafts and approved the final version. All authors had full access to the data and participated in the decision to submit for publication. ClinicalTrials.gov ID: NCT01725906 . Publisher Copyright: {\textcopyright} 2018 AGA Institute",
year = "2018",
month = oct,
day = "1",
doi = "10.1053/j.gastro.2018.06.047",
language = "English",
volume = "155",
pages = "1109--1119",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "4",
}