Tepes 2012.

Methods	Multicentre, prospective, randomised, controlled clinical trial Dates the study was conducted: from 2011 to 2014 Funding sources and potential conflicts of interest: study co‐funded by Slovenian Association for Gastroenterology and Hepatology and a grant from KRKA Pharmaceuticals. No information of conflicts of interest reported Definition of compliance: not defined
Participants	Number and type of participants: 356 H.pylori‐positive participants were enrolled in the study Participants were randomised to 3 different treatment groups: 7‐day standard triple regimen, 10‐day sequential regimen and concomitant therapy for 10 days. For our review only data for the standard and the sequential therapies are relevant Country: Slovenia Number of participants randomised: 356 (ITT sample) Number of participants in the 7‐day STT arm: 116 Number of participants in the 10‐day SEQ arm: 120 Number of participants in the PP analysis: 344 Number of participants in the 7‐day STT arm (PP analysis): 110 Number of participants in the 10‐day SEQ arm (PP analysis): 117 Mean age of the population reported as the number of participants by treatment group: not reported Sex ratio (M/F) per treatment group: 7‐day STT: 57/59 10‐day SEQ: 49/71 Medical condition at baseline by treatment group as n (%) Functional dyspepsia: 7‐day STT: 70 (60.3) 10‐day SEQ: 69 (57.5) Duodenal ulcer: 7‐day STT: 23 (19.8) 10‐day SEQ: 37 (30.8) Gastric ulcer: 7‐day STT: 23 (19.8) 10‐day SEQ: 14 (11.7) H. pylori diagnostic methods in all treatment arms: ¹³C‐urea breath test, rapid urease test, histology and H pylori culture. 2 tests had to be positive for definite diagnosis Sensitivity test (yes/no) to antibiotics before/after treatment: Culture positive biopsy specimens were phenotypically tested for susceptibility to amoxicillin, clarithromycin and metronidazole using gradient diffusion method Metronidazole resistance (%) before treatment: 7‐day STT: 21 (20.4) 10‐day SEQ: 32 (28.3) Clarithromycin resistance (%) before treatment 7‐day STT: 12 (11.0) 10‐day SEQ: 9 (7.8) Dual resistance (%) before treatment 7‐day STT: 5 (6.2) 10‐day SEQ: 6 (7.1)
Interventions	Participants randomised to the SEQ group were administered metronidazole. Length of STT (days): 7 days Name, dose timing of antibiotics in 7‐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+ metronidazole 400 mg twice a day (during 5 days) (Total: 10 days) Method of assessment of H. pylori status after treatment: ¹³C‐urea breath test Time for assessment of H. pylori status after treatment: 4 weeks
Outcomes	ITT eradication rate (%) (95% CI) by treatment group : 7‐day STT: 97/116 (83.6) (76.9 to 90.4) 10‐day SEQ: 113/120 (94.2) (90.0 to 98.4) Metronidazole resistance rate (%) after treatment, ITT analysis 7‐day STT: 16/21 (76.2) 10‐day SEQ: 28/32 (87.5) Clarithromycin resistance rate (%) after treatment, ITT analysis 7‐day STT: 4/12 (33.3) 10‐day SEQ: 6/9 (66.7) PP eradication rate (%) (95% CI) by treatment group: not reported 7‐day STT: 97/110 (88.2) (82.2 to 94.2) 10‐day SEQ: 113/117 (96.6) (93.3 to 99.9) Metronidazole resistance rate (%) after treatment, PP analysis 7‐day STT: not reported 10‐day SEQ: not reported Clarithromycin resistance (%) after treatment, PP analysis 7‐day STT: 16/21 (76.2) 10‐day SEQ: 28/31 (90.3) Adherence rate (%) to therapy by treatment group: not reported Compliance rate (%) by treatment group: reported as "very good" in all treatment arms Incidence rate (%) of AEs by treatment group: 7‐day STT: 21/110 (19) 10‐day SEQ: 25/117 (21) Incidence (%) serious AEs SEQ/STT: not reported
Notes	Author was contacted for further details on methods
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computerised random‐number table
Allocation concealment (selection bias)	Low risk	Investigators in the centres did not know the details of the allocation sequence
Incomplete outcome data (attrition bias) All outcomes	High risk	Eradication rate by treatment group was not reported in the abstract. However, first author provided detailed data when contacted
Blinding of participants and personnel (performance bias) All outcomes	High risk	Treatment was clearly explained to all participants by investigating physician in each participating centre. Study drugs were handed to patients with a day‐by‐ day intake scheme and diagram. Drugs were self‐administered orally at home 30 minutes before meals
Publication format	High risk	Abstract