Sequential Therapy Versus Triple Therapy for Helicobacter Pylori Eradication: a Placebo-Controlled Trial

Condition(s) targeted: Helicobacter Pylori Infection

Intervention: Placebo amoxicillin pantoprazole clarithromycin tinidazole (Drug)

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: St. Orsola Hospital

Official(s) and/or principal investigator(s):
Dino Vaira, M.D., Principal Investigator, Affiliation: S.Orsola/Malpighi Teaching Hospital, University of Bologna, Italy

To assess if a sequential treatment regimen better eradicates H. pylori than does a triple drug regimen in adults with dyspepsia or peptic ulcer disease.

Official title: Sequential Therapy Versus Triple Therapy for Helicobacter Pylori Eradication: a Placebo-Controlled Trial

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: 13C urea breath test, upper endoscopy, histology, rapid urease test assessment

Secondary outcome: bacterial culture, and antibiotic resistance assessment

Detailed description: Background: Antimicrobial resistance has decreased eradication rates for H. pylori worldwide.

Objective: To assess if a sequential treatment regimen better eradicates H. pylori than does a triple drug regimen in adults with dyspepsia or peptic ulcer disease.

Design: Placebo-controlled trial. Setting: Two Italian Hospitals between September 2003 and April 2006. Patients: 300 dyspeptic or peptic ulcer patients Measurements: 13C urea breath test, upper endoscopy, histology, rapid urease test, bacterial culture, and antibiotic resistance assessment.

Intervention: 10-day sequential regimen (pantoprazole 40 mg, amoxicillin 1 g plus placebo for the first 5 days, followed by pantoprazole 40 mg, clarithromycin 500 mg and tinidazole 500 mg for the remaining 5 days) in 150 patients or standard 10-day therapy (pantoprazole 40 mg, clarithromycin 500 mg, and amoxicillin 1 g) in 150 patients. All drugs were given twice daily.

Results: There were 295 patients (Intent to treat) of whom 91% (95% CI: 86. 5–95. 7) had successful eradication with sequential therapy compared to 78% (95% CI: 71. 2–84. 5) for standard therapy (difference: 13. 3%; 95%). The sequential therapy was significantly more effective in patients with clarithromycin resistant strains (88. 9% patients vs. 28. 6%; P = 0. 0034). The incidence of major and minor side effects did not differ between therapy groups (17% vs. 17%).

Limitations: Follow-up was incomplete in 4. 6% and 2. 7% patients in sequential and standard therapy, respectively. The higher efficacy of sequential regimen should be confirmed outside Italy.

Conclusions: Sequential therapy is superior to conventional therapy for the eradication of H. pylori and it is significantly more effective in patients harbouring clarithromycin resistant strains.

The incidence side effects did not differ between therapy groups.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Helicobacter pylori infected patients > 18 years

Exclusion Criteria:

- previous H. pylori eradication treatment;

- Use of proton pump inhibitors, H2-receptor antagonists, bismuth preparations and

antibiotics in the previous 4 weeks;

- Concomitant anticoagulant or ketoconazole use, due to the potential of interaction

with the study medications;

- Zollinger-Ellison syndrome;

- Previous surgery of the esophagus and/or upper gastrointestinal tract (with the

exception of appendectomy, polypectomy and cholecystectomy);

- Severe or unstable cardiovascular, pulmonary, or endocrine disease; clinically

significant renal or hepatic disease or dysfunction; hematological disorder; any other clinically significant medical condition that could increase the risk to the study participants; malignant disease of any kind during the previous 5 years except for successfully treated skin (basal or squamous cell) cancer or Barrett esophagus with high grade dysplasia;

- Drug or medication abuse within the past year;

- Severe psychiatric or neurological disorders;

- Pregnant or nursing women sexually active women of child bearing potential who were

not willing to practice medically acceptable contraception (oral contraceptives; inject able/implantable or mechanical devices as well as vasectomy of the sexual partner) for the entire duration of the study.

S.Orsola/Malpighi Teaching Hospital, University, Bologna 40138, Italy

Related publications:

Zullo A, Gatta L, De Francesco V, Hassan C, Ricci C, Bernabucci V, Cavina M, Ierardi E, Morini S, Vaira D. High rate of Helicobacter pylori eradication with sequential therapy in elderly patients with peptic ulcer: a prospective controlled study. Aliment Pharmacol Ther. 2005 Jun 15;21(12):1419-24.

De Francesco V, Margiotta M, Zullo A, Hassan C, Troiani L, Burattini O, Stella F, Di Leo A, Russo F, Marangi S, Monno R, Stoppino V, Morini S, Panella C, Ierardi E. Clarithromycin-resistant genotypes and eradication of Helicobacter pylori. Ann Intern Med. 2006 Jan 17;144(2):94-100.

Starting date: July 2003
Ending date: February 2006
Last updated: November 22, 2006