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Sequential Therapy versus Standard Triple-Drug Therapy for Helicobacter pylori Eradication
A Randomized Trial
- Dino Vaira, MD;
- Angelo Zullo, MD;
- Nimish Vakil, MD;
- Luigi Gatta, MD;
- Chiara Ricci, MD;
- Federico Perna, PhD;
- Cesare Hassan, MD;
- Veronica Bernabucci, MD;
- Andrea Tampieri, MD; and
- Sergio Morini, MD
- From the University of Bologna, Bologna, Italy; “Nuovo Regina Margherita Hospital,” Rome, Italy; University of Wisconsin, Madison, Wisconsin; and University of Brescia, Brescia, Italy.
Abstract
Background: Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide.
Objective: To determine whether sequential treatment eradicates H. pylori infection better than standard triple-drug therapy for adults with dyspepsia or peptic ulcers.
Design: Randomized, double-blind, placebo-controlled trial.
Setting: Two Italian hospitals between September 2003 and April 2006.
Patients: 300 patients with dyspepsia or peptic ulcers.
Measurements: 13C-urea breath test, upper endoscopy, histologic evaluation, rapid urease test, bacterial culture, and assessment of antibiotic resistance.
Intervention: A 10-day sequential regimen (40 mg of pantoprazole, 1 g of amoxicillin, and placebo, each administered twice daily for the first 5 days, followed by 40 mg of pantoprazole, 500 mg of clarithromycin, and 500 mg of tinidazole, each administered twice daily for the remaining 5 days) or standard 10-day therapy (40 mg of pantoprazole, 500 mg of clarithromycin, and 1 g of amoxicillin, each administered twice daily).
Results: The eradication rate achieved with the sequential regimen was significantly greater than that obtained with the standard treatment in the intention-to-treat analysis (89% vs. 77%; P = 0.0134; difference, 12% [95% CI, 3% to 20%]), the modified intention-to-treat analysis (91% vs. 78%; P = 0.0022; difference, 13% [CI, 5% to 21%]), and the per-protocol analysis (93% vs. 79%; P = 0.0013; difference, 14% [CI, 6% to 21%]). Sequential therapy was significantly more effective in patients with clarithromycin-resistant strains (89% vs. 29%; P = 0.0034). The incidence of major and minor side effects did not differ between therapy groups (17% in both groups). One patient (0.7%) in the standard therapy group discontinued treatment because of side effects.
Limitations: Follow-up was incomplete in 4.6% and 2.7% patients in the sequential therapy and standard therapy groups, respectively. The results may not be generalizable to other countries. Sequential therapy may be more effective because it includes 1 additional antibiotic (tinidazole) that is not contained in standard therapy.
Conclusions: Sequential therapy is statistically significant compared with standard therapy for eradicating H. pylori infection and is statistically significantly more effective in patients with clarithromycin-resistant strains. Side effects are similar with both treatment regimens and are rarely severe enough to cause discontinuation of therapy.
ClinicalTrials.gov registration number: NCT00403364.
For more information on therapy for Helicobacter pylori click here.
Article and Author Information
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Acknowledgments: The authors thank Dr. Alessandra Stancari, S. Orsola Pharmacy, for preparing the medication packages and for maintaining the randomization schedule, and Mrs. Alessandra Guarini, “Nuovo Regina Margherita Hospital,” for nursing assistance.
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Grant Support: Dr. Vakil was a paid attendee at a conference on a gastroesophageal reflux disease diagnostic questionnaire sponsored by Altana Pharma (now Nicomed) (manufacturer of pantoprazole) and was an investigator for a multicenter trial that subsequently evaluated this questionnaire in patients with gastroesophageal reflux disease.
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Potential Financial Conflicts of Interest: Consultancies: N. Vakil (Altana Pharma [now Nicomed]); Stock ownership or options (other than mutual funds): D. Vaira (Meridian Bioscience); Grants received: N. Vakil (Altana Pharma [now Nicomed]).
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Requests for Single Reprints: Dino Vaira, MD, Department of Internal Medicine and Gastroenterology, S. Orsola Hospital, Via Massarenti 9, 40138 Bologna, Italy; e-mail, vairadin{at}med.unibo.it.
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Current Author Addresses: Drs. Vaira, Gatta, Perna, Bernabucci, and Tampieri: Department of Internal Medicine and Gastroenterology, S. Orsola Hospital, Via Massarenti 9, 40138 Bologna, Italy.
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Drs. Zullo, Hassan, and Morini: Gastroenterologia ed Endoscopia Digestiva, Ospedale “Nuovo Regina Margherita,” Via E. Morosini 30, 00153, Rome, Italy.
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Dr. Vakil: Aurora Sinai Medical Center, 945 North 12th Street, Room 4040, Milwaukee, WI 53233.
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Dr. Ricci: Gastroenterology Unit, Spedali Civili, University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy.
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Author Contributions: Conception and design: D. Vaira, A. Zullo, N. Vakil, L. Gatta, C. Ricci.
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Analysis and interpretation of the data: D. Vaira, A. Zullo, N. Vakil, L. Gatta.
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Drafting of the article: D. Vaira, A. Zullo, N. Vakil, L. Gatta.
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Critical revision of the article for important intellectual content: D. Vaira, A. Zullo, N. Vakil, L. Gatta.
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Final approval of the article: D. Vaira, A. Zullo, N. Vakil, L. Gatta, C. Ricci, F. Perna, C. Hassan, V. Bernabucci, A. Tampieri, S. Morini.
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Provision of study materials or patients: D. Vaira, A. Zullo, L. Gatta, C. Ricci, F. Perna, C. Hassan, V. Bernabucci, A. Tampieri, S. Morini.
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Statistical expertise: A. Zullo, N. Vakil, L. Gatta.
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Obtaining of funding: D. Vaira.
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Administrative, technical, or logistic support: D. Vaira.
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Collection and assembly of data: D. Vaira, A. Zullo, L. Gatta.
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