Zhou 2014.

Methods	Prospective, randomised, controlled clinical trial Dates the study was conducted: from March 2008 to December 2010. Funding sources and potential conflicts of interest: study supported by the National Science & Technology Pillar Program of 11th Five‐Year Plan in China (2007BAI04B02). Authors declare no conflicts of interest Definition of compliance: Compliance, determined by pill counts, was defined as good when > 90 % of the prescribed drugs were taken. Participants who had taken 80% of the treatment drugs were considered to show poor compliance and were excluded from the PP analysis Adverse events were evaluated by using open‐ended questions, by participant self reports, and from physical examinations
Participants	Number and type of participants: 280 H.pylori‐positive participants were enrolled in the study Participants were randomised to 2 different treatment groups: 10‐day standard triple regimen and 10‐day sequential regimen Country: China Number of participants randomised: 280 (ITT sample) Number of participants in the 10‐day STT arm: 140 (ITT analysis) Number of participants in the 10‐day STT arm: 128 (PP analysis) Number of participants in the 10‐day SEQ arm: 140 (ITT analysis) Number of participants in the 10‐day SEQ arm: 132 (PP analysis) Mean age of the population (SD) reported as the number of participants by treatment group: 10‐day STT: 43.3 (14.2) 10‐day SEQ: 43.6 (13.1) Sex ratio (M/F) per treatment group 10‐day STT: 71/69 10‐day SEQ: 61/79 Medical condition at baseline, endoscopic findings (NUD/PUD): 10‐day STT: 23/117 10‐day SEQ: 20/120 Antibiotic susceptibility was tested in vitro by the E‐tes from collected H pylori strains. Breakpoints were ≥ 1.0 μg/ml for amoxicillin and clarithromycin and ≥ 8 μg/ml for metronidazole. Isolated CLA‐R was defined as clarithromycin resistance and susceptibility to metronidazole. Isolated MET‐R was defined as metronidazole resistance and susceptibility to clarithromycin. Number of participants with clarithromycin resistance before treatment, n (%): 10‐day STT: 58 (41.4) 10‐day SEQ: 54 (38.6) Number of participants with metronidazole resistance before treatment, n (%): 10‐day STT: 91 (65.0) 10‐day SEQ: 96 (68.6) H. pylori diagnostic methods in all treatment arms: endoscopy with a gastric biopsy taken from the antrum was subjected to a RUT. If the result was positive, 2 additional specimens (from the antrum and corpus) were obtained for H. pylori culture. Participants with positive cultures were classified as being infected with H. pylori
Interventions	Participants randomised to the SEQ group were administered tinidazole Length of STT (days): 10 days Name, dose timing of antibiotics in 10‐day STT: esomeprazole 20 mg twice a day, clarithromycin 500 mg twice a day, amoxicillin 1g twice a day Name, dose timing of antibiotics in 10‐day SEQ: esomeprazole 20 mg twice a day + amoxicillin 1g twice a day (during 5 days) and esomeprazole 20 mg twice a day, clarithromycin 500 mg twice a day+ tinidazole 500mg twice a day (during 5 days) (Total: 10 days) Sensitivity test (yes/no) to antibiotics before/after treatment: Performed but method not specified Method of assessment of H. pylori status after treatment: ¹³C‐urea breath test Time for assessment of H. pylori status after treatment: 8 ‐ 12 weeks
Outcomes	ITT eradication rate (%) by treatment group : 10‐day STT: 93/140 (66.4) 10‐day SEQ: 101140 (72.1) PP eradication rate (%) by treatment group: 10‐day STT: 93/128 (72.7) 10‐day SEQ: 101/132 (76.5) Adherence rate (%) (95% CI) to therapy by treatment group: not reported Effect of antibiotic resistances on H pylori eradication proportions in the PP population, by treatment arm: ‐ Clarithromycin resistance rate (%) (amoxicillin and metronidazole susceptible): 10‐day STT: 7/16 (43.8) 10‐day SEQ: 8/9 (88.9) ‐ Metronidazole resistance rate (%) (amoxicillin and clarithromycin susceptible): 10‐day STT: 39/43 (90.7) 10‐day SEQ: 41/47 (87.2) ‐ Dual resistance rate (%) (clarithromycin and metronidazole resistance and amoxicillin susceptible): 10‐day STT: 18/34 (52.9) 10‐day SEQ: 17/37 (45.9) Incidence of AEs by treatment group (n, %): not reported Incidence (%) serious AEs SEQ / STT: not reported
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A computer‐generated randomisation scheme (SAS version 8.0; SAS Institute, Cary, NC), with stratification by centre, was constructed using a block design (block size of 4) by an independent statistician and was used to determine treatment allocation
Allocation concealment (selection bias)	Low risk	Allocation was concealed by the use of opaque envelopes that were opened by the investigator when the participant was eligible for the study and had provided written informed consent. The endoscopists, pathologists, and technicians who performed RUT and UBT were all blinded to the treatment group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Primary outcome data were clearly reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The participants were randomly assigned to treatment in a 1:1 ratio within 2 weeks of a positive culture result
Publication format	Low risk	Full article