Jyh-Ming Liou1, Yu-Jen Fang2, Chieh-Chang Chen1, Ming-Jong Bair3, Chi-Yang Chang4, Yi-Chia Lee1, Mei-Jyh Chen1, Chien-Chuan Chen1, Cheng-Hao Tseng4, Yao-Chun Hsu4, Ji-Yuh Lee2, Tsung-Hua Yang2, Jiing-Chyuan Luo5, Chun-Chao Chang6, Chi-Yi Chen7, Po-Yueh Chen7, Chia-Tung Shun8, Wen-Feng Hsu9, Wen-Hao Hu9, Yen-Nien Chen9, Bor-Shyang Sheu10, Jaw-Town Lin11, Jeng-Yih Wu12, Emad M El-Omar13, Ming-Shiang Wu14. 1. Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. 2. Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, National Taiwan University College of Medicine, Yun-Lin, Taiwan. 3. Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan; Department of Nursing, Meiho University, Pingtung, Taiwan. 4. Department of Internal Medicine, E-DA Hospital and I-Shou University, Kaohsiung County, Taiwan. 5. Department of Medicine, National Yang-Ming University, School of Medicine, and Taipei Veterans General Hospital, Taipei, Taiwan. 6. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital and School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 7. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chia-Yi Christian Hospital, Chia-Yi, Taiwan. 8. Department of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. 9. Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan. 10. Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; National Cheng Kung University Medical Center, Tainan, Taiwan. 11. 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. 12. Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 13. Department of Medicine, St George & Sutherland Clinical School, University of New South Wales, Sydney, Australia. 14. Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: mingshiang@ntu.edu.tw.
Abstract
BACKGROUND: Whether concomitant therapy is superior to bismuth quadruple therapy or 14-day triple therapy for the first-line treatment of Helicobacter pylori infection remains poorly understood. We aimed to compare the efficacy and safety of 10-day concomitant therapy, 10-day bismuth quadruple therapy, and 14-day triple therapy in the first-line treatment of H pylori. METHODS: In this multicentre, open-label, randomised trial, we recruited adult patients (aged >20 years) with H pylori infection from nine medical centres in Taiwan. Patients who had at least two positive tests from the rapid urease test, histology, culture, or serology or who had a single positive 13C-urea breath test for gastric cancer screening were eligible for enrolment. Patients were randomly assigned (1:1:1) to either concomitant therapy (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily) for 10 days; bismuth quadruple therapy (bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day) for 10 days; or triple therapy (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily) for 14 days. A computer-generated permuted block randomisation sequence with a block size of 6 was used for randomisation, and the sequence was concealed in an opaque envelope until the intervention was assigned. Investigators were masked to treatment allocation. The primary outcome was the eradication frequency of H pylori with first-line therapy assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01906879. FINDINGS:Between July 17, 2013, and April 20, 2016, 5454 patients were screened for eligibility. Of these, 1620 patients were randomly assigned in this study. The eradication frequencies were 90·4% (488/540 [95% CI 87·6-92·6]) for 10-day bismuth quadruple therapy, 85·9% (464/540 [82·7-88·6]) for 10-day concomitant therapy, and 83·7% (452/540 [80·4-86·6]) for 14-day triple therapy in the intention-to-treat analysis. 10-day bismuth quadruple therapy was superior to 14-day triple therapy (difference 6·7% [95% CI 2·7-10·7, p=0·001), but not 10-day concomitant therapy. 10-day concomitant therapy was not superior to 14-day triple therapy. The frequency of adverse events was 67% (358/533) in patients treated with 10-day bismuth quadruple therapy, 58% (309/535) in patients treated with 10-day concomitant therapy, and 47% (252/535) in patients treated with 14-day triple therapy. INTERPRETATION:Bismuth quadruple therapy is preferable to 14-day triple therapy in the first-line treatment in the face of rising prevalence of clarithromycin resistance. Concomitant therapy given for 10 days might not be optimum and a longer treatment length should be considered. FUNDING: National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.
RCT Entities:
BACKGROUND: Whether concomitant therapy is superior to bismuth quadruple therapy or 14-day triple therapy for the first-line treatment of Helicobacter pylori infection remains poorly understood. We aimed to compare the efficacy and safety of 10-day concomitant therapy, 10-day bismuth quadruple therapy, and 14-day triple therapy in the first-line treatment of H pylori. METHODS: In this multicentre, open-label, randomised trial, we recruited adult patients (aged >20 years) with H pylori infection from nine medical centres in Taiwan. Patients who had at least two positive tests from the rapid urease test, histology, culture, or serology or who had a single positive 13C-urea breath test for gastric cancer screening were eligible for enrolment. Patients were randomly assigned (1:1:1) to either concomitant therapy (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily) for 10 days; bismuth quadruple therapy (bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day) for 10 days; or triple therapy (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily) for 14 days. A computer-generated permuted block randomisation sequence with a block size of 6 was used for randomisation, and the sequence was concealed in an opaque envelope until the intervention was assigned. Investigators were masked to treatment allocation. The primary outcome was the eradication frequency of H pylori with first-line therapy assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01906879. FINDINGS: Between July 17, 2013, and April 20, 2016, 5454 patients were screened for eligibility. Of these, 1620 patients were randomly assigned in this study. The eradication frequencies were 90·4% (488/540 [95% CI 87·6-92·6]) for 10-day bismuth quadruple therapy, 85·9% (464/540 [82·7-88·6]) for 10-day concomitant therapy, and 83·7% (452/540 [80·4-86·6]) for 14-day triple therapy in the intention-to-treat analysis. 10-day bismuth quadruple therapy was superior to 14-day triple therapy (difference 6·7% [95% CI 2·7-10·7, p=0·001), but not 10-day concomitant therapy. 10-day concomitant therapy was not superior to 14-day triple therapy. The frequency of adverse events was 67% (358/533) in patients treated with 10-day bismuth quadruple therapy, 58% (309/535) in patients treated with 10-day concomitant therapy, and 47% (252/535) in patients treated with 14-day triple therapy. INTERPRETATION:Bismuth quadruple therapy is preferable to 14-day triple therapy in the first-line treatment in the face of rising prevalence of clarithromycin resistance. Concomitant therapy given for 10 days might not be optimum and a longer treatment length should be considered. FUNDING: National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.
Authors: Mohd Amer Alsamman; Eric C Vecchio; Khaled Shawwa; Gabriel Acosta-Gonzales; Murray B Resnick; Steven F Moss Journal: Dig Dis Sci Date: 2019-06-11 Impact factor: 3.199