Triple Therapy Versus Quadruple Therapies in the First Line Therapy of Helicobacter Pylori Infection

Comparison of the Efficacy of Clarithromycin-based Triple Therapy Versus Quadruple Therapies in the First Line Therapy of Helicobacter Pylori Infection- A Multicenter Randomized Comparative Trial

Whether non-bismuth quadruple therapy (concomitant therapy) is more effective than bismuth quadruple therapy or triple therapy for 14 days remains unknown.

Therefore, we aim to compare the eradication rates and long term re-infection rates of quadruple therapy for 10 days versus non-bismuth quadruple therapy for 10 days vs. triple therapy for 14 days.

Methods: This will be a multi-center, open labeled, randomized control trial Patients: H. pylori infected patients who have willingness to receive eradication therapy

Testing for H. pylori infection Before First Line Ttreatment

(1)Any two positive of rapid urease test, histology, serology and culture or a positive UBT will be considered as H. pylori infected

After First Line Treatment: C13-Urea breath test will be used to assess the existence of H. pylori 6-8 weeks after first line therapy.

Long term reinfection: C13- Urea breath test will be used to assess the recurrence of H. pylori 1 year after eradication therapy

Study Overview

• Status: Unknown
• Conditions: Helicobacter Pylori Infection
• Intervention / Treatment: Drug: triple, quadruple, non-bismuth quadruple therapy

Detailed Description

First line therapy: open labeled, randomized control trial, randomized into one of the three groups Group (A): triple therapy for 14 days D1-D14: (lansoprazole 30mg + clarithromycin 500mg + amoxicillin 1gm) bid Group (B): non-bismuth quadruple therapy for 10 days D1-D10: lansoprazole 30mg bid + amoxicillin 1gm bid + clarithromycin 500mg bid + metronidazole 500mg bid Group (C): bismuth quadruple therapy for 10 days D1-D10: lansoprazole 30mg bid + colloidal bismuth subcitrate 300mg tid + metronidazole 500mg tid + tetracycline 500mg tid

Second line therapy: patients who fail from first line treatment will be rescue with the following treatment Group (A) Patient who fail from triple therapy will be retreated with bismuth quadruple therapy for 10 days D1-D10: lansoprazole 30mg bid + colloidal bismuth subcitrate 300mg tid + metronidazole 500mg tid + tetracycline 500mg tid Group (B) Patient who fail from non-bismuth quadruple therapy will be retreated with bismuth quadruple therapy for 10 days D1-D10: lansoprazole 30mg bid + colloidal bismuth subcitrate 300mg tid + metronidazole 500mg tid + tetracycline 500mg tid Group (C) Patients who fail from bismuth quadruple therapy will be retreated with non-bismuth quadruple therapy for 10 days D1-D10: lansoprazole 30mg bid + amoxicillin 1gm bid + clarithromycin 500mg bid + metronidazole 500mg bid

• Study Type: Interventional
• Enrollment (Anticipated): 1620
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Chiayi, Taiwan
    • Recruiting
    • Chiayi Christian Hospital
    • Contact: Po-ye Chen
  • Hsinchu, Taiwan
    • Recruiting
    • National Taiwan University Hospital, Hsinchu Branch
    • Contact: Wen Fong Hsu, MD
    • Principal Investigator: Wen Fong Hsu, MD
  • Kaohsiung, Taiwan
    • Recruiting
    • E- DA Hospital and I-Shou University
    • Contact: Chi-Yang Chang, MD
    • Principal Investigator: Chi Yang Chang, MD
  • Kaohsiung, Taiwan
    • Recruiting
    • Kaohsiung Medical University Hospital
    • Contact: Jeng-Yih Wu
  • Taipei, Taiwan
    • Recruiting
    • Taipei Medical University Hospital
    • Contact: Chun-Chao Chen
  • Taipei, Taiwan
    • Recruiting
    • Taipei Veterans General Hospital
    • Contact: Jiing-Chyuan Luo, MD
    • Principal Investigator: Jiing-Chyuan Luo, MD
  • Taipei, Taiwan, 10002
    • Recruiting
    • Ming-Shiang Wu
    • Contact: Jyh-Ming Liou, MD, PhD
    • Principal Investigator: Ming-Shiang Wu, MD, PHD
    • Principal Investigator: Jyh-Ming Liou, MD, PhD
    • Sub-Investigator: Mei-Jyh Chen, MD
    • Sub-Investigator: Chien-Chun Chen, MD
  • Taipei, Taiwan
    • Recruiting
    • Mackay Memorial Hospital, Taipei
    • Contact: Wen-Hsiung Chang, MD
    • Principal Investigator: Wen-Hsiung Chang, MD
  • Taitung, Taiwan
    • Recruiting
    • Mackay Memorial Hospital, Taitung
    • Contact: Ming Chung Bair, MD
    • Principal Investigator: Ming Chung Bair, MD
  • Yun-Lin County, Taiwan
    • Recruiting
    • National Taiwan University Hospital, Yun-Lin Branch
    • Contact: Chieh-Chang Chen, MD
    • Principal Investigator: Chieh-Chang Chan, MD
    • Sub-Investigator: Ji-Yuh Lee, MD
    • Sub-Investigator: Yu-Jen Fang, MD
    • Principal Investigator: Chi-Yang Chang, MD

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:

Patients aged greater than 20 years who have H. pylori infection without prior eradication therapy and are willing to receive the sequential therapy will be eligible for enrolment. Written informed consents will be obtained from all patients prior to enrollment.

Exclusion Criteria:

Patients will be excluded from the study if any one of the following criteria is present: (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 (amoxicillin, clarithromycin, metronidazole, or levofloxacin) and prompt pump inhibitors (lansoprazole), (5)contraindication to treatment drugs, (6) pregnant or lactating women, (7) severe concurrent diseases, and (8) Patients who cannot give informed consent by himself or herself.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Triple therapy (A); lansoprazole, 30mg, twice daily, for 14 days, po clarithromycin, 500mg, twice daily, for 14 days, po amoxicillin, 1gm, twice daily, for 14 days, po	Drug: triple, quadruple, non-bismuth quadruple therapy; triple therapy, quadruple therapy, non-bismuth quadruple therapy; Other Names: Group (A): triple therapy for 14 days; Group (B): non-bismuth quadruple therapy for 10 days; Group (C): bismuth quadruple therapy for 10 days
Experimental: non-bismuth quadruple therapy; Group (B): non-bismuth quadruple therapy for 10 days: lansoprazole 30mg bid + amoxicillin 1gm bid + clarithromycin 500mg bid + metronidazole 500mg bid	Drug: triple, quadruple, non-bismuth quadruple therapy; triple therapy, quadruple therapy, non-bismuth quadruple therapy; Other Names: Group (A): triple therapy for 14 days; Group (B): non-bismuth quadruple therapy for 10 days; Group (C): bismuth quadruple therapy for 10 days
Experimental: bismuth quadruple therapy for 10 days; Group (C): bismuth quadruple therapy for 10 days D1-D10: lansoprazole 30mg bid + colloidal bismuth subcitrate 300mg tid + metronidazole 500mg tid + tetracycline 500mg tid	Drug: triple, quadruple, non-bismuth quadruple therapy; triple therapy, quadruple therapy, non-bismuth quadruple therapy; Other Names: Group (A): triple therapy for 14 days; Group (B): non-bismuth quadruple therapy for 10 days; Group (C): bismuth quadruple therapy for 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eradication rate for H. pylori	Eradication rate in the first line according to intention to treat (ITT) and per-protocol (PP) analysis in the three treatment groups	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse effects of each treatments	(1) Incidence of adverse effects in the first line therapy in the three treatment groups	2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reinfection rate	Eradication rates in the second line treatment in the three treatment groups; Overall eradication rates after first line and second line treatment in the three treatment groups; Antibiotic resistance of gut flora after first line and second line treatments in the three treatment groups; Changes of gut microbiota in the three treatment groups; Re-infection rate one year after eradication therapy	1 year

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Ming-Shiang Wu, MD. PhD, National Taiwan University Hospital, Taipei, Taiwan

Publications and helpful links

General Publications

• Liou JM, Chen CC, Chang CM, Fang YJ, Bair MJ, Chen PY, Chang CY, Hsu YC, Chen MJ, Chen CC, Lee JY, Yang TH, Luo JC, Chen CY, Hsu WF, Chen YN, Wu JY, Lin JT, Lu TP, Chuang EY, El-Omar EM, Wu MS; Taiwan Gastrointestinal Disease and Helicobacter Consortium. Long-term changes of gut microbiota, antibiotic resistance, and metabolic parameters after Helicobacter pylori eradication: a multicentre, open-label, randomised trial. Lancet Infect Dis. 2019 Oct;19(10):1109-1120. doi: 10.1016/S1473-3099(19)30272-5.
• Liou JM, Fang YJ, Chen CC, Bair MJ, Chang CY, Lee YC, Chen MJ, Chen CC, Tseng CH, Hsu YC, Lee JY, Yang TH, Luo JC, Chang CC, Chen CY, Chen PY, Shun CT, Hsu WF, Hu WH, Chen YN, Sheu BS, Lin JT, Wu JY, El-Omar EM, Wu MS; Taiwan Gastrointestinal Disease and Helicobacter Consortium. Concomitant, bismuth quadruple, and 14-day triple therapy in the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet. 2016 Nov 12;388(10058):2355-2365. doi: 10.1016/S0140-6736(16)31409-X. Epub 2016 Oct 18.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: July 21, 2013
• First Submitted That Met QC Criteria: July 21, 2013
• First Posted (Estimate): July 24, 2013

Study Record Updates

• Last Update Posted (Actual): June 12, 2017
• Last Update Submitted That Met QC Criteria: June 9, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• 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; Gastrointestinal Agents; Antacids; Bismuth
• Other Study ID Numbers: 201304017MINB

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