Clinical trial NCT01219764: A Trial of Standard vs Half Dose Rabeprazole, Clarithromycin, Metronidazole and Amoxicillin in the Treatment of Helicobacter Pylori Infection
Official title: A Randomized Trial of Standard vs Half Dose Rabeprazole, Clarithromycin, Metronidazole and Amoxicillin in the Treatment of Helicobacter Pylori Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Helicobacter Infections
Keywords: Helicobacter pylori infection
quadruple therapy
Amoxicillin
Metronidazole
Clarithromycin
Rabeprazole
Lead sponsor: American University of Beirut Medical Center
Sponsor class: OTHER
First posted: 2010-10-13
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The proposed study will test the hypothesis that H. pylori can be eradicated successfully (\>85%) using half-or full-dose "concomitant" non-bismuth quadruple therapy regimen: rabeprazole, amoxicillin, clarithromycin and metronidazole twice daily for 7 days in patients with peptic ulcers and H. pylori related gastritis.

Two hundred patients from the outpatient department and the endoscopy unit at AUBMC will be enrolled in this open-label trial. Patients with positive CLO tests or urea breath tests, documenting H.pylori infection, will be randomized into one of two groups: Full dose or half dose the concomitant regimen, with 100 patients in each group. Compliance and side effects will be assessed, and a urea breath test will be done for all patients after 4 weeks of therapy completion to evaluate eradication rates. Success of therapy will be evaluated according to intent-to treat and per-protocol analyses.

Detailed description: Infection with H. pylori has been linked with chronic active gastritis, peptic ulcer disease, adenocarcinoma and Non-Hodgkin's lymphoma of the stomach. Eradication of this organism has been recommended for patients with peptic ulcer disease, low-grade gastric mucosa-associated lymphoid tissue lymphoma, atrophic gastritis, unexplained iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, as well as first-degree relatives of gastric cancer patients.

Guidelines still recommend using triple therapy regimen of PPI, clarithromycin and amoxicillin/metronidazole twice daily for 7 to 14 days. Over the years, it has become clear that the first-line triple therapy is loosing efficacy worldwide with PP and ITT eradication rates inferior to 80%. Antimicrobial resistance plays an important role in some of these failures.

Major H. pylori study groups in the world have agreed that alternative treatment regimens are urgently needed. So far, 2 alternative treatment regimens have shown superiority over the first-line treatment protocols: the sequential therapy consisting of a combination of amoxicillin and a PPI twice a day for 5 days followed by another 5 days of the PPI plus clarithromycin and tinidazole/metronidazole, and the concomitant non-bismuth quadruple regimen consisting of PPI, clarithromycin, metronidazole, and amoxicillin twice daily.

The proposed study will test the hypothesis that H. pylori can be eradicated successfully (\>85%) using half-or full-dose "concomitant" non-bismuth quadruple therapy regimen: rabeprazole, amoxicillin, clarithromycin and metronidazole twice daily for 7 days in patients with peptic ulcers and H. pylori related gastritis.

Two hundred patients from the outpatient department and the endoscopy unit at AUBMC will be enrolled in this open-label trial. Patients with positive CLO tests or urea breath tests, documenting H.pylori infection, will be randomized into one of two groups: Full dose or half dose the concomitant regimen, with 100 patients in each group. Compliance and side effects will be assessed, and a urea breath test will be done for all patients after 4 weeks of therapy completion to evaluate eradication rates. Success of therapy will be evaluated according to intent-to treat and per-protocol analyses.

Eligibility criteria: Inclusion Criteria:

* documented H.pylori infection by a CLO test or a Urea Breath Test
* sign the informed consent

Exclusion Criteria:

* Age under 18 or older than 80 years
* Allergies to any of the drugs used
* Recent antibiotic therapy (within 2 weeks of enrolment)
* Severe ulcers or bleeding
* Gastric perforation or obstruction
* Previous gastrectomy
* Gastric cancer
* Pregnancy or lactation
* Prior eradication therapy for H. pylori
* Severe concomitant disease or condition making the treatment unlikely to be effective i.e. alcoholism, drug addiction, and history of poor compliance.

Primary outcomes:
measure: Number of participants with negative urea breath test post treatment
timeFrame: 30 days post treatment completion
Secondary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: during the 7 days of the treatment
Other outcomes:
Locations:
city: Beirut
country: Lebanon
facility: American University of Beirut - Medical Center
Study officials:
affiliation: American University of Beirut Medical Center
name: Ala' I Sharara, MD
role: PRINCIPAL_INVESTIGATOR
References: