Efficacy of High Dose Dual Therapy, Sequential Therapy and Triple Therapy in H. Pylori Eradication

Sponsor

National Taiwan University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01163435

Collaborator

National Science Council, Taiwan (Other)

618

Enrollment

Location

Arms

Duration (Months)

16.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Up to now, to our knowledge, there is few randomized, large scale study prospectively and simultaneously comparing the efficacy, adverse effects and patient adherence of these current recommended 1st-line or 2nd-line regimens for H. pylori eradication in and out of our country.

The aims of this study are:

to compare the efficacy of high dose dual therapy, sequential therapy and clarithromycin-based triple therapy as 1st-line regimen in H. pylori eradication;
to compare the efficacy of high dose dual therapy, sequential therapy and levofloxacin-based triple therapy as rescue regimen in H. pylori eradication;
to compare the patient adherence and adverse effects of these treatment regimens;
to investigate factors that may influence H. pylori eradication by these treatment regimens;
to investigate and analyze the prevalence and trend of antibiotic resistance.

Condition or Disease	Intervention/Treatment	Phase
Helicobacter Infection	Drug: high dose dual therapy Drug: sequential therapy Drug: clarithromycin-based triple therapy Drug: levofloxacin-based triple therapy	Phase 4

Detailed Description

Patients having H. pylori-positive chronic gastritis with/without peptic ulcers will be recruited. All undergo endoscopy with biopsy before treatment. Four to eight weeks after termination of treatment, H. pylori infection status will be examined by endoscopy with biopsy or the Carbon 13-urea breath test if the patients refuse the second endoscopy. The cytochrome P450 (CYP) 2C19 genotype of each participant will be analyzed by the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. A computed generated random numbers sequence will be blocked into three subgroups, say A1, B1 and C1 (or A2, B2, and C2).

If the patients did not receive anti-H. pylori therapy previously, they will be invited to enter the first part of study for evaluating the efficacy of 1st-line regimens. If the patients had received anti-H. pylori therapy previously, they will be invited to enter the second part of study for evaluating the efficacy of rescue regimens. Patients who meet the inclusion criteria and do not have any one of the exclusion criteria will be randomized to receive one of the following regimens:

for 1st-line regimens: group A1 - high dose dual therapy (rabeprazole 20 mg qid + amoxicillin 750 mg qid for 14 days); group B1 - sequential therapy (rabeprazole 20 mg + amoxicillin 1000 mg, bid for 5 days, then rabeprazole 20 mg + metronidazole 500 mg + clarithromycin 500 mg, bid for next 5 days); group C1 - clarithromycin-based triple therapy (rabeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg, bid for 7 days).
for rescue regimens: group A2 - high dose dual therapy (as group A1); group B2 - sequential therapy (as group B1); group C2 - levofloxacin-based triple therapy (rabeprazole 20 mg + amoxicillin 1000 mg + levofloxacin 250 mg, bid for 7 days).

All patients will be asked to complete a questionnaire and to record symptoms and drug consumption daily during the treatment period. Post-treatment, the patients were seen at the Outpatients Clinic to investigate patient adherence and adverse effects of treatment.

Study Design

Study Type:

Interventional

Actual Enrollment :

618 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy of High Dose Dual Therapy, Sequential Therapy and Triple Therapy in H. Pylori Eradication - A Prospective, Comparative Study

Study Start Date :

Aug 1, 2010

Actual Primary Completion Date :

Jul 1, 2013

Actual Study Completion Date :

Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: high dose dual therapy group A1 and A2 - high dose dual therapy (rabeprazole 20 mg qid, amoxicillin 750 mg qid for 14 days)	Drug: high dose dual therapy rabeprazole 20 mg qid,amoxicillin 750 mg qid for 14 days
Experimental: sequential therapy group B1 and B2 - sequential therapy (rabeprazole 20 mg, amoxicillin 1000 mg, bid for 5 days, then rabeprazole 20 mg , metronidazole 500 mg, clarithromycin 500 mg, bid for next 5 days)	Drug: sequential therapy rabeprazole 20 mg, amoxicillin 1000 mg, bid for 5 days, then rabeprazole 20 mg , metronidazole 500 mg, clarithromycin 500 mg, bid for next 5 days
Active Comparator: clarithromycin-based triple therapy group C1 - clarithromycin-based triple therapy (rabeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, bid for 7 days)	Drug: clarithromycin-based triple therapy rabeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, bid for 7 days
Active Comparator: levofloxacin-based triple therapy group C2 - levofloxacin-based triple therapy (rabeprazole 20 mg, amoxicillin 1000 mg, levofloxacin 250 mg, bid for 7 days)	Drug: levofloxacin-based triple therapy rabeprazole 20 mg, amoxicillin 1000 mg, levofloxacin 250 mg, bid for 7 days

Outcome Measures

Primary Outcome Measures

to compare the efficacy, adverse effects and patient adherence of high dose dual therapy, sequential therapy and clarithromycin-based triple therapy (or levofloxacin-based triple therapy) as 1st-line regimen (or rescue regimen) in H. pylori eradication [3.5 years]
The eradication rates (efficacy) will be evaluated by intention-to-treat (ITT) and per-protocol (PP) analysis. The safety and tolerability will be evaluated by the number of participant with adverse events and patient adherence (by counting unused medication after the treatment).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

patients having H. pylori related chronic gastritis with/without peptic ulcers who are aged greater than 18 years and are willing to received eradication therapy.

Exclusion Criteria:

pregnant or nursing woman
serious concomitant illness and malignant tumor of any kind
history of hypersensitivity to test drugs
serious bleeding during the course of this ulcer
previous gastric surgery
receiving bismuth salts, proton pump inhibitors, or antibiotics in the previous month.