Efficacy of High-dose Dual Therapy vs Bismuth-containing Quadruple Therapy for Rescue Treatment of Hp Infection

Efficacy of High-dose Dual Therapy Versus Bismuth-containing Quadruple Therapy for Rescue Treatment of Helicobacter Pylori Infection - A Prospective, Randomized, Comparative Study

Up to now, there is few randomized, large scale study prospectively and simultaneously comparing the efficacy, adverse effects and patient adherence of high-dose dual therapy (HDDT) and bismuth-containing quadruple therapy (BQT) as rescue regimens for H. pylori eradication.

The aims of this study are:

1. to compare the efficacy of HDDT, and BQT as rescue regimen in H. pylori eradication;
2. to compare the patient adherence and adverse effects of these treatment regimens;
3. to investigate factors that may influence H. pylori eradication by these treatment regimens.

Study Overview

• Status: Completed
• Conditions: Helicobacter Pylori Infection
• Intervention / Treatment: Drug: High-dose dual therapy (rabeprazole, amoxicillin); Drug: Bismuth-containing quadruple therapy (rabeprazole, tripotassium dicitrate bismuthate, metronidazole, tetracycline)

Detailed Description

Participants, aged ≥ 20, having H. pylori-positive chronic gastritis with/without peptic ulcers (duodenal or gastric ulcers) will be recruited. All undergo endoscopy with biopsy for rapid urease teat, histology, and bacterial culture before treatment. Four to eight weeks after termination of treatment, H. pylori infection status will be examined by the 13C-urea breath test. The CYP2C19 genotype of each participant will be analyzed by the polymerase chain reaction-based restriction fragment length polymerase (PCR-RFLP) method. A computed generated random numbers sequence will be blocked into two subgroups, say A, and B.

If the patients failed anti-H. pylori therapy previously, they will be invited to enter this study for evaluating the efficacy of these rescue regimens. Participant 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:

group A- HDDT (rabeprazole 20 mg qid + amoxicillin 750 mg qid for 14 days);

group B- BQT ( rabeprazole 20 mg qid + tripotassium dicitrate bismuthate 300 mg qid + metronidazole 250 mg qid + tetracycline 500 mg qid for 10 days);

All participants will be asked to complete a questionnaire and to record symptoms and drug consumption daily during the treatment period. Post-treatment, the participants will be followed up at the Outpatients Clinic to investigate patient adherence and adverse effect of treatment.

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Participants having H. pylori related chronic gastritis with/without peptic ulcers who are aged greater than 20 years old and are willing to received eradication therapy.

Exclusion criteria:

1. pregnant or nursing woman
2. serious concomitant illness and malignant tumor of any kind
3. history of hypersensitivity to test drugs
4. serious bleeding during the course of the ulcer
5. previous gastric surgery
6. receiving bismuth salts, PPIs, 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-dose dual therapy; group A-high-dose dual therapy ( rabeprazole 20 mg, tablet, qid + amoxicillin 750 mg, capsule, qid for 14 days)	Drug: High-dose dual therapy (rabeprazole, amoxicillin); High-dose dual therapy ( rabeprazole 20 mg qid + amoxicillin 750 mg qid for 14 days); Other Names: Proton pump inhibitor, Rabeprazole, Pariet®; Antibiotics, Amoxicillin ,Amoxicillin®
Active Comparator: Bismuth-containing quadruple therapy; group B-bismuth-containing quadruple therapy (rabeprazole 20 mg, tablet, bid + tripotassium dicitrate bismuthate 300 mg, tablet, qid + metronidazole 250 mg, tablet, qid + tetracycline 500 mg qid, capsule, for 10 days)	Drug: Bismuth-containing quadruple therapy (rabeprazole, tripotassium dicitrate bismuthate, metronidazole, tetracycline); Bismuth-containing quadruple therapy (rabeprazole 20 mg bid + tripotassium dicitrate bismuthate 300 mg qid + metronidazole 250 mg qid + tetracycline 500 mg qid for 10 days); Other Names: Proton pump inhibitor, Rabeprazole, Pariet®; Antibiotics, Metronidazole, Flagyl®; Antibiotics, Tetracycline, Tetracycline®; Colloidal Bismuth, Tripotassium dicitrate bismuthate, KCB®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The eradication rates as a measure of the efficacy of HDDT, and BQT	The eradication rates (efficacy) will be evaluated by intention-to-treat (ITT) and per-protocol (PP) analysis.	3.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse effects as a measure of safety	The safety will be evaluated by counting the number of participant with adverse events.	3.5 years
Amount of unused medication post treatment as a measure of patient adherence.	The patient adherence will be evaluated by counting unused medication after the treatment.	3.5 years

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): January 1, 2019

Study Registration Dates

• First Submitted: July 2, 2015
• First Submitted That Met QC Criteria: July 6, 2015
• First Posted (Estimate): July 7, 2015

Study Record Updates

• Last Update Posted (Actual): April 29, 2020
• Last Update Submitted That Met QC Criteria: April 27, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Helicobacter pylori; high dose dual therapy; bismuth-containing quadruple therapy; antibiotic resistance
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Helicobacter Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Anti-Ulcer Agents; Antitubercular Agents; Antacids; Metronidazole; Anti-Bacterial Agents; Antibiotics, Antitubercular; Rabeprazole; Amoxicillin; Bismuth; Tetracycline; Proton Pump Inhibitors
• Other Study ID Numbers: 201504037MINB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No