1. LOGO Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-lable, randomised trial 杨 天 1311210631 Epidemiology and Biostatistics March 31, 2014

2. LOGO Contents Introduction Methods Procedures Statistical analysis Results Discussion

3. LOGO Introduction Sequential treatment  a proton-pump inhibitor and amoxicillin for the first 5 days ；  proton-pump inhibitor plus clarithroycin and metronidazole (or tinidazole) for another 5 days. Triple therapy  7 days or 10 days

4. LOGO Concerns  Susceptibility tests;  Generalised to other countries;  Few studies, contradictory results, reasons unknown;  The effectiveness of extending the duration of sequential treatment from 10 days to 14 days.

5. LOGO Concerns  Re-treat the patients who fail sequential treatment;  To choose the best regimen on the basis of the prevalence of antibiotic resistance in different geographical areas;

6. LOGO A randomised controlled trial  The efficacy of sequential treatment for 10 days and 14 days with triple therapy for 14 daysin firstline treatment;  Eradication rates;  The efficacy of the modified sequential treatment;  The efficacies of three regimens in the sensitivity analysis.

7. LOGO Methods ： Study design and participants  Gastroenterology clinics in six medical centres in Taiwan.  Aged 20 years or older;  Documented H pylory infection.

8. LOGO The criteria of exclusion of the study  Previous eradication treatment for H pylory;  History of gastrectomy;  Contraindication or previous allergic reactions to the study drugs;  Pregnant or lactating women  Use of antibiotics within the previous 4 weeks;  Severe concurrent diseases or malignancy.

9. LOGO Randomisation and masking A permuted block randomisation; An independent research assistant; The computerised random number sequence; An opaque envelop All investigators were masked. T-14 lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg for 14 days. S-10 lansoprazole 30 mg and amoxicillin 1 g for the first 5 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg for another 5 days. S-14 lansoprazole 30 mg and amoxicillin 1 g for the first 7 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg for another 7 days. Procedures for the first-line treatment.

10. LOGO Procedures Before enrolment Post-treatment H pylori status Patients with positive results: rapid urease test, histology, culture, and serology. Asymptomatic individuals who underwent screening: positive C urea breath test. TC urea breath test (C-UBT): stop treatment with proton-pump inhibitor and histamin-2 blocker for at least 2 weeks. Primary endpoint: H pylori eradication rates in first-line treatment. Secondary endpoints: the frequency of adverse events and compliance.

11. LOGO Figure 1. Trial profile ITT=intention-to-treat. PP=per-protocol. MS-14=modified sequential treatment containing levofloxacin. S-10=sequential treatment for 10 days. S-14=sequential treatment for 14 days. T14=triple therapy for 14 days.

12. LOGO Statistical analysis  Sample size: 300 individuals in each group  Power: 90%  Chi-square test or Fisher's exact test  Student's t test  Multiple logistic regression analyses  A decision model  Deterministic and probabilistic sensitivity analyses.

13. LOGO Table1: Baseline characteristics

14. LOGO Table 2: Helicobacter pylory eradication in first-line and second-line treatments

15. LOGO Figure 2: Efficacies of first-line and second-line Helicobacter pylory treatments

16. LOGO Table 3: Adverse events in first-line and second-line treatment

17. LOGO Table 4: Factors affecting eradication first-line treatment

18. LOGO Appendix

19. LOGO

20. Discussion: Novel findings  Sequential treatment for 14 days is better than triple therapy for 14 days as first-line treatment;  Clarithromycin resistance decreased the efficacies of both sequential and triple treatments;  Metronidazole resistance decreased the efficacy of sequential treatment;

21. LOGO Novel findings  H pylory eradication rates are not affected by host CYP2C19 polymorphisms nor bacterial virulence factors;  Modified sequential treatment containing levofloxacin is effective for patients who failed from either sequential or triple therapy.

22. LOGO Strengths  Large sample size;  Comparison of three treatment groups;  Factors that might affect treatment efficacy;  The efficacy of their recue treatment;  The sensitivity analysis according to the prevalence of antibiotic resistance.

23. LOGO Limitations  Selection bias;  The difference in the overall efficacy after first-line and second- line treatment;  The precision in the efficacy estimate of MS-14 was constrained;

24. LOGO Limitations  The complexity of sequential treatment might reduce patients' compliance outside clinical trials;  The allocation concealment;  The differences between S-14 and S-10 and between S-10 and T-14 were not statisticaly significant.

25. LOGO Summary  All the findings lend support to the use of sequential treatment as the standard first-line treatment for H pylori infection.  They also lend support to the idea that the best eradication regimen should be chosen on the basis of the prevalence of antibiotic- resistant H pylori in the region.

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