The Efficacy of the 7 Days Tailored Therapy as 2nd Rescue Therapy for Eradication of H. Pylori Infection

A Prospective, Single-center, Randomized, Open-label, Parallel Design Clinical Trial to Compare the 14-day Bismuth Quadruple Therapy and 7-day Culture Based Tailored Therapy for the Eradication of Helicobacter as a Rescue 2nd Therapy.

As increasing the antibiotics resistance, the effectiveness of traditional Helicobacter pylori (H. pylori) therapies has been declined coincidentally.

In this study, the investigators evaluated the efficacy of H. pylori eradication between a 7 days personalized therapy for H. pylori infection based on the results of antibiotics resistance by using H. pylori culture and minimal inhibitory concentration (MIC) and the 14 days bismuth contained quadruple 2nd rescue regimens, and the investigators analyzed the prevalence of the antibiotic resistance after 1st eradication of H. pylori in the tailored therapy group.

Study Overview

• Status: Terminated
• Conditions: Helicobacter Infection
• Intervention / Treatment: Drug: Metronidazole; Drug: Moxifloxacin; Drug: Amoxicillin; Drug: Tetracycline; Drug: tripotassium dicitrate bismuthate; Drug: 14 days empirical bismuth quadruple therapy (Proton pump inhibitor); Procedure: H. pylori culture and antimicrobial susceptibility testing; Drug: 7 days tailored therapy Proton Pump Inhibitor

Detailed Description

The patients who had shown the evidence of persistent H. pylori infection after the 1st eradication were enrolled for this study.

After giving the informed consent about the method and efficacy (ITT and PP analysis) of the 14 days bismuth quadruple 2nd rescue therapy and the 7 days tailored therapy for H. pylori infection based on culture and MIC, the patients were randomly classified into the two regimen group under the patient's agreement and underwent 2nd eradication [14 days bismuth-based quadruple therapy (Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d.), or 7 days tailored therapy based on H. pylori culture and MIC (select the 2nd rescue regimen between 7 days of bismuth-based quadruple therapy or 7 days moxifloxacin-containing triple therapy (PPI regular dose b.i.d., moxifloxacin 400 mg q.d., and amoxicillin 1g b.i.d.) according to antibiotics susceptibility.

This study was designed to evaluate the success of eradication for enrolled participants by methods of an open labelled randomized prospectively.

• Study Type: Interventional
• Enrollment (Actual): 370
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nayoung Kim, M.D., Ph. D; Phone Number: 82-31-787-7008; Email: nayoungkim49@empas.com

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
      • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• The patients who proved a failure of 1st eradication of H. pylori with Proton pump inhibitor based triple therapy (PPI bid + amoxacillin 1g b.i.d + Clarithromycin 500 mg b.i.d) or sequential therapy (initial 5-day therapy with a combination of PPI b.i.d and amoxicillin 1g b.i.d, followed by 5 days of PPI b.i.d., clarithromycin 500mg b.i.d., and metronidazole 500mg t.i.d) following three methods

  1. positive rapid urease test (CLOtest)
  2. histologic evidence of H. pylori by modified Giemsa staining
  3. positive 13C-Urea breath test
• Male and female Korean Adult (Aged ≥ 18 years)

Exclusion Criteria:

• Patients who received two or more eradication therapy for H. pylori infection
• H. pylori eradication failure because of poor compliance
• the administration of antibiotics or the consumption of bismuth salts within 4 weeks or the administration of a proton pump inhibitor (PPI) within 2 weeks
• Advanced gastric cancer or other malignancy
• Abnormal liver function or liver cirrhosis
• Abnormal renal function or chronic kidney disease
• Other severe concurrent diseases
• Previous allergic reactions to the study drugs
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 14 days PBMT group; Giving the 14 days bismuth quadruple regimen as 2nd rescue therapy for eradication of persistent H. pylori infection Drug regimen Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d	Drug: Metronidazole; Drug: Tetracycline; Drug: tripotassium dicitrate bismuthate; Drug: 14 days empirical bismuth quadruple therapy (Proton pump inhibitor); Giving the 14 days PBMT regimen as 2nd rescue therapy Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d.
Experimental: 7 days tailored therapy group; According the antimicrobial susceptibility testing, the H. pylori isolates were resistant to moxifloxacin, 7 days PBMT regimen were prescribed; if the isolates were resistant to metronidazole, 7 days moxiflxacin based triple regimen (PPI regular dose b.i.d., moxifloxacin 400 mg q.d., and amoxicillin 1g b.i.d) were prescribed.	Drug: Moxifloxacin; Drug: Amoxicillin; Procedure: H. pylori culture and antimicrobial susceptibility testing; This intervention will be performed in 7 days tailored therapy group. All the patients who enrolled in this arm, they will be received endoscopy guided biopsy procedure. Minimum inhibitory concentrations (MICs) were determined by the agar dilution method. Amoxicillin, clarithromycin, metronidazo, tetracycline and moxifloxacin for the H. pylori isolates were examined by use of the serial two fold agar dilution method; Drug: 7 days tailored therapy Proton Pump Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the percentage of participants with successful H. pylori eradication in each groups	The efficacy of H. pylori eradication between a 7 days tailored therapy for H. pylori infection based on the results of antimicrobial resistance by using H. pylori culture and minimal inhibitory concentration (MIC) and the 14 days bismuth quadruple therapy as 2nd rescue regimens. The eradication rate was evaluated by intention to treat (ITT) and per-protocol (PP) analysis	6 weeks after completion of eradication

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital
• Investigators: Principal Investigator: Nayoung Kim, M.D., Ph. D, Seoul National University Bundang Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: February 4, 2015
• First Submitted That Met QC Criteria: February 9, 2015
• First Posted (Estimate): February 10, 2015

Study Record Updates

• Last Update Posted (Actual): April 13, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Helicobacter pylori; resistance; rescue therapy
• Additional Relevant MeSH Terms: Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Helicobacter Infections; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Gastrointestinal Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antacids; Moxifloxacin; Metronidazole; Anti-Bacterial Agents; Amoxicillin; Anti-Infective Agents; Bismuth; Tetracycline; Proton Pump Inhibitors
• Other Study ID Numbers: B1408/285-005