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Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, ope

n-lable, randomised trial

杨 天1311210631

Epidemiology and Biostatistics

March 31, 2014

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Contents

Introduction

Methods

Procedures

Statistical analysis

Results

Discussion

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Introduction

Sequential treatmenta proton-pump inhibitor and amoxicillin

for the first 5 days ；proton-pump inhibitor plus clarithroyci

n and metronidazole (or tinidazole) for another 5 days.

Triple therapy7 days or 10 days

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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.

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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;

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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.

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Methods ： Study design and participants

Gastroenterology clinics in six medical centres in Taiwan.

Aged 20 years or older;Documented H pylory infection.

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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.

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Randomisation and masking

• A permuted block rando

misation;

• 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.

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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.

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Figure 1. Trial profileITT=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.

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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.

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Table1: Baseline characteristics

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

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

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

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Table 4: Factors affecting eradication first-line treatment

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Appendix

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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;

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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.

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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.

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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;

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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.

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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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