Jyh-Ming Liou1, Po-Yueh Chen2, Jiing-Chyuan Luo3, Ji-Yuh Lee4, Chieh-Chang Chen1, Yu-Jen Fang4, Tsung-Hua Yang4, Chi-Yang Chang5, Ming-Jong Bair6, Mei-Jyh Chen1, Yao-Chun Hsu5, Wen-Feng Hsu1, Chun-Chao Chang7, Jaw-Town Lin8, Chia-Tung Shun9, Emad M El-Omar10, Ming-Shiang Wu11. 1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. 2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chia-Yi Christian Hospital, Chia-Yi, Taiwan. 3. Department of Medicine, National Yang-Ming University, School of Medicine, and Taipei Veterans General Hospital, Taipei, Taiwan. 4. Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, National Taiwan University College of Medicine, Yun-Lin, Taiwan. 5. School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. 6. Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan and Mackay Medical College, New Taipei City, Taiwan. 7. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 8. Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. 9. Department of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. 10. Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia. 11. Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: mingshiang@ntu.edu.tw.
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 givendoxycycline 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.
RCT Entities:
BACKGROUND & AIMS: We aimed to compare the efficacy of genotypic resistance-guided therapy vs empirical therapy for eradication of refractory Helicobacter pyloriinfection 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.