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. 2016 Jun 28;2016(6):CD009034. doi: 10.1002/14651858.CD009034.pub2

Liou 2013.

Methods Randomised, open‐label, multicentre trial.
Dates the study was conducted: from December 2009 to September 2011
Funding sources and potential conflicts of interest: study funded by the National Taiwan University Hospital and National Science Council. Authors declare no conflicts of interest.
Definition of compliance: defined as low when < 80% of pills were taken
Participants Number and type of participants: 900 H.pylori‐positive participants were enrolled in the study
Participants were randomised to 3 different treatment groups: 14‐day standard triple regimen, 10‐day sequential regimen and 14‐day sequential regimen. Only data referring to the 7‐day STT and 10‐day SEQ are relevant
Number of participants randomised: 900 (ITT sample)
Number of participants in the 14‐day STT arm, ITT analysis: 300
Number of participants in the 10‐day SEQ arm, ITT analysis: 300
Number of participants in the 14‐day STT arm, PP analysis: 279
Number of participants in the 10‐day SEQ arm, PP analysis: 285
Country: China
Average age (SD) of the population in years reported by treatment group:

  • 14‐day STT: 53.3 (14.1)

  • 10‐day SEQ: 52.8 (13.8)


Sex proportions as the number of M/F in the ITT population by treatment group:

  • 14‐day STT: 167/133

  • 10‐day SEQ: 159/141


Medical condition (PUD participants) at baseline reported as number of participants (%) in the

  • 14‐day STT: 197/300 (66%)

  • 10‐day SEQ: 209/300 (70%)


Baseline resistance for every antibiotic as the number of participants (%) or participants positive/participants tested (%):
Metronidazole ITT resistance (%) before treatment, 10‐day SEQ: 46/192 (24%)
Metronidazole ITT resistance (%) before treatment, 14‐day STT: 48/183 (26%)
Clarithromycin ITT resistance (%) before treatment, 10‐SEQ: 21/183 (11%)
Clarithromycin ITT resistance (%) before treatment, 14‐day STT: 18/192 (9%)
Amoxicillin ITT resistance (%) before treatment, 10‐day SEQ: 4/192 (2%)
Amoxicillin ITT resistance (%) before treatment, 14‐day STT: 5/183 (3%)
Levofloxacin ITT resistance (%) before treatment, 10‐day SEQ: 22/183 (12%)
Levofloxacin ITT resistance (%) before treatment, 14‐day STT: 22/192 (11%)
H. pylori diagnostic methods in both treatment arms: serology, RUT, histology, culture, UBT
Participants with positive results in at least 2 of these tests were eligible for enrolment
Interventions Participants randomised to the SEQ group were administered metronidazole
Name, dose timing of antibiotics in 14‐day STT:
lansoprazole 30 mg twice a day + clarithromycin 500 mg twice a day + amoxicillin 1 g twice a day (during 14 days)
Length of STT (days): 14
Name, dose timing of antibiotics in 10‐day SEQ:
lansoprazole 30 mg twice a day + amoxicillin 1 g twice a day (during 5 days) and lansoprazole 30 mg twice a day + clarithromycin 500 mg twice a day + metronidazole 500 mg twice a day (during 5 days) (Total: 10 days)
Sensitivity test (yes/no) to antibiotics before/after treatment: Yes. probabilistic sensitivity tests were performed to investigate the effects of changes in the prevalence of the antibiotic resistant strains
Method of assessment of H. pylori status after treatment: ¹³ C‐urea breath test
Time for assessment of H. pylori status after treatment: 6 weeks
Outcomes The study flow chart showed that after randomisation, in the 14‐day STT arm there were 21 dropouts, whereas in the 10‐day SEQ there were 15 dropouts
ITT eradication rate (%) (95% CI) by treatment group:

  • 14‐day STT: 247/300 (82.3) (78.0 to 86.6)

  • 10‐day SEQ: 261/300 (87.0) (83.2 to 90.8)


PP eradication rate (%) (95%CI) by treatment group :

  • 14‐day STT: 243/279 (87.1) (83.2 to 91.0)

  • 10‐day SEQ: 258/285 (90.5) (87.1 to 93.9)


ITT eradication rate (%) in PUD participants:

  • 14‐day STT: 161/179 (90)

  • 10‐day SEQ: 180/199 (90)


ITT eradication rate (%) in NUD participants:

  • 14‐day STT: 82/100 (82)

  • 10‐day SEQ: 78/86 (91)


Univariate analysis of post‐treatment antibiotic susceptibilities and resistances in the 10‐day SEQ and 14‐day STT respectively:
Clarithromycin resistance rates (%) (resistant ‐R and susceptible ‐S strains) (phenotypic) in 10‐day SEQ and 14‐STT groups respectively

  • Cla‐S: 152/166 (92) ‐ 137/151 (91)

  • Cla‐R: 10/17 (59) ‐ 11/20 (55)


Metronidazole resistance rates (%) (resistant ‐R and susceptible ‐S strains) (phenotypic) in 10‐day SEQ and 14‐STT groups respectively:

  • Met‐S: 130/139 (94) ‐ 107/125 (86)

  • Met‐R: 32/44 (73) ‐ 41/46 (89)


Amoxicillin resistance rates (%) (resistant ‐R and susceptible ‐S strains) (phenotypic) in 10‐day SEQ and 14‐STT groups respectively

  • Amoxi‐S: 160/179 (89) ‐ 147/166 (89)

  • Amoxi‐R: 2/4 (50) ‐ 1/5 (20)


Clarithromycin (Cla) and metronidazole (Met) resistance rates (%) (resistant ‐R and susceptible ‐S strains) (phenotypic) in 10‐day SEQ and 14‐STT groups respectively

  • Cla‐S and Met‐S: 123/129 (95) ‐ 98/109 (90)*

  • Cla‐S and Met‐R: 29/37 (78) ‐ 39/42 (93)

  • Cla‐R and Met‐S: 7/10 (70) ‐ 9/16 (56)

  • Cla‐R and Met‐R: 3/7 (43) ‐ 2/4 (50)


Compliance rate (%) in ITT sample (took at least 80% of the drugs)

  • 10‐day SEQ: 258/285 (91)

  • 14‐day STT: 243/278 (87)


Number of patients (%) that did not take the 80% of the drugs:

  • 10‐day SEQ: 3/3 (100)

  • 14‐day STT: 4/7 (57)


Type and Incidence rate (%) of AEs reported in the 10‐day SEQ/14‐day STT arms respectively:
Diziness: 31/295 (11)/19/299 (6)
Skin rash: 9/295 (3)/7/299 (2)
Headache: 9/295 (3)/16/299 (5)
Taste distortion: 58/295 (20)/76/299 (25)
Abdominal pain: 19/295 (6)/31/299 (10)
Nausea: 23/295 (8)/11/299 (4)
Diarrhoea: 48/295 (16)/62/299 (21)
Constipation: 9/295 (3)/11/299 (4)
Bloating: 21/295 (7)/17/299 (6)
Any type of adverse events: 142/294 (48)/164/298 (55)
Number of patients out of the total (%) that discontinued drugs because of AEs in the 10‐day SEQ/14‐day STT arms respectively: 6/295 (2)/13/297 (4)
Incidence rate (%) of serious AEs SEQ / STT: not reported
Notes  
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk The trial was truly randomised. A permuted block randomisation method with a block size of 6 was used. An independent research assistant at the National Taiwan University Hospital generated the computerised random number sequence
Allocation concealment (selection bias) Low risk The sequence was concealed in an opaque envelope until the intervention was assigned. After the written informed consents were obtained from eligible participants, the independent research assistant telephoned study staff to give them each participant’s treatment allocation
Incomplete outcome data (attrition bias) 
 All outcomes Low risk Outcome data were clearly reported
Blinding of participants and personnel (performance bias) 
 All outcomes Unclear risk All investigators were masked to the randomisation sequence
Publication format Low risk Full article