Clinical trial NCT00403364: Sequential Therapy Versus Triple Therapy for Helicobacter Pylori Eradication: a Placebo-controlled Trial
Official title: Sequential Therapy Versus Triple Therapy for Helicobacter Pylori Eradication: a Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Helicobacter Pylori Infection
Keywords: Helicobacter pylori infection
Treatment
Double blind placebo controlled trial
Lead sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Sponsor class: OTHER
First posted: 2006-11-23
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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.

Primary outcomes:
measure: 13C urea breath test, upper endoscopy, histology, rapid urease test assessment
Secondary outcomes:
measure: bacterial culture, and antibiotic resistance assessment
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: S.Orsola/Malpighi Teaching Hospital, University
Study officials:
affiliation: S.Orsola/Malpighi Teaching Hospital, University of Bologna, Italy
name: Dino Vaira, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.