Sequential Therapy Versus Quadruple Therapy in H. Pylori Eradication

Comparison of the Efficacy of Sequential Therapy and Bismuth Quadruple Therapy in the First Line and Second Line Therapy for Helicobacter Pylori Infection- A Multi-center Randomized Trial

The investigators aimed to

1. compare the eradication rates and long term re-infection rates of sequential therapy for 14 days versus bismuth quadruple therapy for 10 days in the first line and second line treatment
2. assess the impact of antibiotic resistance and CYP2C19 polymorphism on the eradication rate of these regimens
3. assess the impact of these eradication regimens on the antibiotic resistance and microbiota of the gut flora
4. assess the impact of eradication therapy on the metabolic factors

Study Overview

• Status: Unknown
• Conditions: Helicobacter
• Intervention / Treatment: Drug: 14-day sequential therapy; Drug: Bismuth quadruple therapy

Detailed Description

Helicobacter pylori infection has been shown to be associated with the development of gastric cancer and peptic ulcer diseases. Eradication of H. pylori infection reduces the risk of gastric cancer and recurrence of peptic ulcer disease. However, the eradication rate of clarithromycin-based triple therapy has been declining in recent years, probably related to the increasing resistant rate to clarithromycin. Sequential therapy for 10 days has been shown to be more effective than triple therapy for 7 and 10 days. The investigators further demonstrated that sequential therapy given for 14 days was superior to triple therapy given for 14 days. Recently, the investigators also found that bismuth quadruple therapy given for 10 days appeared to be more effective than triple therapy given for 14 days in the first line therapy. However, whether sequential therapy given for 14 days is more effective than bismuth quadruple therapy or triple therapy for 14 days remains unknown.

• Study Type: Interventional
• Enrollment (Anticipated): 620
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jyh-Ming Liou, MD, PhD; Email: dtmed046@pchome.com.tw

Study Locations

• Taiwan
  • Chiayi City, Taiwan
    • Recruiting
    • Chiayi Christian Hospital
    • Contact: Po-Yuei Chen
  • Hsinchu, Taiwan
    • Recruiting
    • National Taiwan University Hospital, Hsinchu Branch
    • Contact: Wen-Feng Hsu
  • Kaohsiung, Taiwan
    • Recruiting
    • E-DA University Hospital
    • Contact: Chi-Yang Chang, MD
  • Taipei, Taiwan
    • Recruiting
    • Taipei Veteran General Hospital
    • Contact: Jing-Chuang Luo
  • Taipei, Taiwan
    • Recruiting
    • Jyh-Ming Liou
    • Contact: Jyh-Ming Liou, MD, PhD; Phone Number: 886972651883; Email: jyhmingliou@gmail.com
  • Taitung, Taiwan
    • Recruiting
    • Mackay Memorial Hospital, Taitung branch
    • Contact: Ming-Chung Bair
  • Yunlin County, Taiwan
    • Recruiting
    • National Taiwan University Hospital, Yun-Lin Branch
    • Contact: Yu-Ren Fang, MD; Phone Number: 886972655474

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. H. pylori infected patients naïve to eradication therapies will be eligible in this study.

Exclusion Criteria:

1. children and teenagers aged less than 20 years,
2. history of gastrectomy,
3. gastric malignancy, including adenocarcinoma and lymphoma,
4. previous allergic reaction to antibiotics (bismuth, amoxicillin, metronidazole, clarithromycin, tetracycline) and PPI (esomeprazole),
5. contraindication to treatment drugs,
6. pregnant or lactating women,
7. severe concurrent disease,
8. concomitant use of clopidogrel, or (9) Unwilling to accept random assignment of subjects

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: sequential therapy for 14 days (S14); 14 day sequential therapy	Drug: 14-day sequential therapy; D1-D7: (esomeprazole 40mg qid + amoxicillin 500mg qid) for 7 days D8-D14: (esomeprazole 40mg qid + clarithromycin 500mg bid + metronidazole 500mg bid) for another 7 days; Other Names: S14
Active Comparator: bismuth quadruple therapy (Q10); Bismuth quadruple therapy	Drug: Bismuth quadruple therapy; D1-D10: (esomeprazole 40mg bid + dibismuth trioxide 120mg qid + metronidazole 500mg tid + tetracycline 500mg qid) for 10 days; Other Names: Q10

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eradication rate: determined by urea breath test (13C-UBT, according to ITT analysis)	No eradicated divided by total cases by intention to treat analysis. 13C-UBT will be used to determine the H. pylori status at least 6 weeks after completion of treatment. A delta value of > 4 units will be defined as positive for H. pylori infection as our previous studies.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse effect: occurrence of any adverse effect during the treatment	adverse effects related to treatment by per protocol analysis. The patients will be informed of the common side effects from the studied drugs prior to therapy. They will also be asked to record these symptoms during treatment. A standardized interview at the outpatient clinic at the end of treatment will be arranged. The adverse events and compliance will be assessed by the research staffs with pre-defined case report form.	2 weeks
changes of antibiotic resistance	changes of antibiotic resistance of E. coli by per protocol analysis	2 weeks, 8 weeks, 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes of gut microbiota	changes of gut microbiota before and after HP eradication by per protocol analysis	2 weeks, 8 weeks, 1 year

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Mackay Memorial Hospital; Taipei Veterans General Hospital, Taiwan; Kaohsiung Medical University; Chiayi Christian Hospital; E-DA Hospital; National Taiwan University Hospital Hsin-Chu Branch
• Investigators: Study Director: Ming-Shiang Wu, MD, PhD, National Taiwan University Hospital

Publications and helpful links

General Publications

• Liou JM, Chen CC, Fang YJ, Chen PY, Chang CY, Chou CK, Chen MJ, Tseng CH, Lee JY, Yang TH, Chiu MC, Yu JJ, Kuo CC, Luo JC, Hsu WF, Hu WH, Tsai MH, Lin JT, Shun CT, Twu G, Lee YC, Bair MJ, Wu MS; Members of the Taiwan Gastrointestinal Disease and Helicobacter Consortium. 14 day sequential therapy versus 10 day bismuth quadruple therapy containing high-dose esomeprazole in the first-line and second-line treatment of Helicobacter pylori: a multicentre, non-inferiority, randomized trial. J Antimicrob Chemother. 2018 Sep 1;73(9):2510-2518. doi: 10.1093/jac/dky183.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: September 30, 2015
• First Submitted That Met QC Criteria: May 16, 2017
• First Posted (Actual): May 17, 2017

Study Record Updates

• Last Update Posted (Actual): May 17, 2017
• Last Update Submitted That Met QC Criteria: May 16, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: safety; efficacy; H. pylori eradication
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Antacids; Bismuth
• Other Study ID Numbers: 201506129MINC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No