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

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

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:

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

Study Overview

• Status: Completed
• Conditions: Helicobacter Infection
• Intervention / Treatment: Drug: high dose dual therapy; Drug: sequential therapy; Drug: clarithromycin-based triple therapy; Drug: levofloxacin-based triple therapy

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 Type: Interventional
• Enrollment (Actual): 618
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 10043
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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).	3.5 years

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: National Science Council, Taiwan

Publications and helpful links

General Publications

• Yang JC, Lin CJ, Wang HL, Chen JD, Kao JY, Shun CT, Lu CW, Lin BR, Shieh MJ, Chang MC, Chang YT, Wei SC, Lin LC, Yeh WC, Kuo JS, Tung CC, Leong YL, Wang TH, Wong JM. High-dose dual therapy is superior to standard first-line or rescue therapy for Helicobacter pylori infection. Clin Gastroenterol Hepatol. 2015 May;13(5):895-905.e5. doi: 10.1016/j.cgh.2014.10.036. Epub 2014 Nov 14.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: July 1, 2010
• First Submitted That Met QC Criteria: July 14, 2010
• First Posted (Estimate): July 15, 2010

Study Record Updates

• Last Update Posted (Estimate): December 3, 2013
• Last Update Submitted That Met QC Criteria: December 1, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Helicobacter pylori; high dose dual therapy; antibiotic resistance; sequential therapy; clarithromycin-based triple therapy; levofloxacin-based triple therapy
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Helicobacter Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Clarithromycin; Levofloxacin; Ofloxacin
• Other Study ID Numbers: 200912093M