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

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.

Study Overview

• Status: Completed
• Conditions: Helicobacter Pylori Infection
• Intervention / Treatment: Drug: Placebo amoxicillin pantoprazole clarithromycin tinidazole

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.

• Study Type: Interventional
• Enrollment: 300
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
13C urea breath test, upper endoscopy, histology, rapid urease test assessment

Secondary Outcome Measures

Outcome Measure
bacterial culture, and antibiotic resistance assessment

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Dino Vaira, M.D., S.Orsola/Malpighi Teaching Hospital, University of Bologna, Italy

Publications and helpful links

General 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. doi: 10.1111/j.1365-2036.2005.02519.x.
• 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. doi: 10.7326/0003-4819-144-2-200601170-00006.
• Vaira D, Zullo A, Vakil N, Gatta L, Ricci C, Perna F, Hassan C, Bernabucci V, Tampieri A, Morini S. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial. Ann Intern Med. 2007 Apr 17;146(8):556-63. doi: 10.7326/0003-4819-146-8-200704170-00006.

Study record dates

Study Major Dates

• Study Start: July 1, 2003
• Study Completion: February 1, 2006

Study Registration Dates

• First Submitted: November 22, 2006
• First Submitted That Met QC Criteria: November 22, 2006
• First Posted (Estimate): November 23, 2006

Study Record Updates

• Last Update Posted (Actual): March 18, 2021
• Last Update Submitted That Met QC Criteria: March 17, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Treatment; Helicobacter pylori infection; Double blind placebo controlled trial
• Additional Relevant MeSH Terms: Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Helicobacter Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Alkylating Agents; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Antitrichomonal Agents; Amoxicillin; Clarithromycin; Tinidazole; Pantoprazole
• Other Study ID Numbers: 1112/2006; No grant received