Original article—alimentary tract
Sequential and Concomitant Therapy With Four Drugs Is Equally Effective for Eradication of H pylori Infection

https://doi.org/10.1016/j.cgh.2009.09.030Get rights and content

Background & Aims

Sequential therapy with a proton pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole agent reportedly have a better rate of curing Helicobacter pylori infection than PPI, amoxicillin, and clarithromycin triple therapy. The concomitant administration of these 4 drugs (concomitant therapy) is also an effective treatment strategy. We compared the efficacies of sequential and concomitant therapy and analyzed the effects of antibiotic resistance in patients with H pylori infection.

Methods

In a randomized trial of 232 H pylori-infected patients from 3 hospitals in Kaohsiung, Taiwan, patients were given 10 days of sequential (n = 115) or concomitant (n = 117) therapy. H pylori status was confirmed by endoscopy or urea breath test.

Results

Intention-to-treat analysis demonstrated similar eradication rates for sequential (92.3%; 95% confidence interval [CI], 87.5%–97.1%) and concomitant therapy (93.0%; 95% CI, 88.3%–97.7%)(P = .83). Per-protocol eradication results were similar for sequential (93.1%; 95% CI, 90.7%–95.5%) and concomitant therapy (93.0%; 95% CI, 88.3%–97.7%) (P = .99). Univariate analysis showed that compliance and resistance to clarithromycin were independent determinants of eradication. Dual resistance did not influence the level of eradication in the concomitant group, but significantly affected that of the sequential therapy group. Clarithromycin resistance was less frequent than expected.

Conclusions

Sequential or concomitant therapy with a PPI, amoxicillin, clarithromycin, and an imidazole agent are equally effective and safe for eradication of H pylori infection. Resistance to clarithromycin, compliance, and adverse events reduced the level of eradication. Concomitant therapy may be more suitable for patients with dual resistance to antibiotics.

Section snippets

Setting and Participants

We surveyed patients who visited the gastroenterology clinics of Kaohsiung Medical University Hospital, Kaohsiung Veteran General Hospital, and Kaohsiung Municipal Hsiao-Kang Hospital between June 2007 and May 2008.

Patients with H pylori infection were enrolled in this study. Pre-enrollment procedures included biopsy of the gastric mucosa where the presence of H pylori was assessed by histological examination of the tissue, culture, and rapid urease testing. The presence of H pylori was defined

Characteristics of the Study Groups

A total of 232 H. pylori-infected patients were randomly assigned to sequential (n = 115) or concomitant (n = 117) therapies (see Supplementary Figure 1). The first patient was randomized on February 26, 2007 and the last ended treatment on January 25, 2008. The subjects were all included in the ITT analysis for H pylori eradication. The baseline demographic and clinical characteristics of patients at entry are summarized in Table 1. The 2 groups had comparable age, gender, history of smoking,

Discussion

H pylori eradication rate following triple therapies has substantially decreased, requiring a search for novel therapeutic approaches to cure H pylori infections.16 Sequential therapy was one approach to overcoming the resistance problem, and our study showed that the administration of a PPI and 3 antibiotics, whether given sequentially or concomitantly, had good success. It also showed that there appears to be nothing special with the sequential approach, which may be more complicated than is

Acknowledgments

The authors thank Dr Claudia A. Kozinetz for the assistance with study design.

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    Conflict of interest The authors disclose the following: In the last 3 years, Dr Graham has received small amounts of grant support and/or free drugs, or urea breath tests from Meretek, and BioHit for investigator-initiated and completely investigator-controlled research. Dr Graham is a consultant for Novartis in relation to vaccine development for treatment or prevention of H pylori infection. Dr Graham is a also a paid consultant for Otsuka Pharmaceuticals and until July 2007 was a member of the Board of Directors of Meretek Diagnostics, the manufacturer of the 13C-urea breath test. Dr Graham will receive royalties on the Baylor College of Medicine patent covering materials related to 13C-urea breath test until October 2009. The remaining authors disclose no conflicts.

    Funding This study was funded in part by the National Science Council of the ROC (NSC-98-2314-B-037-004-MY2), Center of Excellence for Environmental Medicine, Kaohsiung Medical University and National Sun Yat-Sen University-Kaohsiung Medical University Joint Center. Role of the funding source: Funding only, no involvement in design or analysis. Dr Graham is supported in part by Public Health Service grant DK56338 which funds the Texas Medical Center Digestive Diseases Center and R01 CA116845. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the VA or NIH.

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