Sequential Versus Quadruple Therapy in the Second-line Treatment

Comparison of the Efficacy of 14-day Sequential Therapy and 10-day Bismuth Quadruple Therapy in the Second Line Therapy for Helicobacter Pylori Infection: A Multi-center Randomized Trial

Objectives: A recent randomized trial showed that 14-day sequential therapy containing high dose proton pump inhibitor was higher than 95% in the first line treatment. However, whether the 14-day sequential therapy is more effective than 10-day bismuth quadruple therapy remains unknown. Therefore, the investigators aimed to 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 second line treatment.

Study Overview

• Status: Unknown
• Conditions: Helicobacter Pylori Infection
• Intervention / Treatment: Drug: Esomeprazole (S14); Drug: Amoxicillin (ST14); Drug: Clarithromycin (ST14); Drug: Metronidazole (ST14); Drug: Esomeprazole (BQ10); Drug: dibismuth trioxide 120mg (BQ10); Drug: Metronidazole (BQ10); Drug: tetracycline (BQ10)

Detailed Description

This will be a multi-center, open labeled, randomized comparative trial Patients: 240 patients with H. pylori infection who failed after first-line therapy will be eligible

Interventions: eligible patients will be randomized into one of the two groups Group (A): sequential therapy for 14 days (S14)

D1-D7: (esomeprazole 40mg bid + amoxicillin 1000mg bid) for 7 days

D8-D14: (esomeprazole 40mg bid + clarithromycin 500mg bid + metronidazole 500mg bid) for another 7 days

Group (B): bismuth quadruple therapy for 10 days (Q10)

D1-D10: (esomeprazole 40mg bid + dibismuth trioxide 120mg qid + metronidazole 500mg tid + tetracycline 500mg qid) for 10 days

Primary End Point: Eradication rate in the second line treatment according to intention to treat (ITT) analysis in the two treatment groups

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jyh-Ming Liou, MD, PhD; Phone Number: 63541 886-2-23123456; Email: jyhmingliou@gmail.com
• Study Contact Backup: Name: Ming-Shiang Wu, MD, PhD; Phone Number: 65043 886-2-23123456; Email: mingshiang@ntu.edu.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, Taiwan, 10002
    • Recruiting
    • Jyh-Ming Liou
    • Principal Investigator: Ming-Shiang Wu
    • Principal Investigator: Yu-Jen Fang

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:

• H. pylori infected patients who fail from first line standard triple therapy with clarithromycin, amoxicillin, and a proton pump inhibitor will be eligible in this study.

Exclusion Criteria:

Patients will be excluded from the study if any one of the following criteria was present:

• children and teenagers aged less than 20 years,
• history of gastrectomy,
• gastric malignancy, including adenocarcinoma and lymphoma,
• previous allergic reaction to antibiotics (bismuth, metronidazole, levofloxacin, tetracycline) and PPI (esomeprazole),
• contraindication to treatment drugs,
• pregnant or lactating women,
• severe concurrent disease, or
• 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: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequential therapy for 14 days; Sequential therapy for 14 days (experimental) D1-D7: (Nexium, esomeprazole 40mg bid + amoxicillin (Brand name: Amoxicillin Capsule) 1000mg bid) for 7 days D8-D14: (Nexium, esomeprazole 40mg bid + Klaricid XL, clarithromycin 500mg bid + Flagyl, metronidazole 500mg bid) for another 7 days	Drug: Esomeprazole (S14); Nexium, esomeprazole 40mg bid, 14 days; Other Names: Nexium; Drug: Amoxicillin (ST14); Day 1-7 amoxicillin (Brand name: Amoxicillin Capsule) 1000mg bid for 7 days; Other Names: amoxicillin capsule; Drug: Clarithromycin (ST14); Klaricid-XL, clarithromycin, 500mg, bid, for 7 days, (day 8-14); Other Names: Klaricid-XL 500mg; Drug: Metronidazole (ST14); Flagyl, metronidazole, 500mg bid, for 7 days (day 8-14); Other Names: Flagyl
Active Comparator: bismuth quadruple therapy for 10 days; Bismuth quadruple therapy for 10 days (active comparator) D1-D10: (Nexium, esomeprazole 40mg bid + KCB F.C. TABLETS, dibismuth trioxide 120mg qid + Flagyl, metronidazole 500mg tid + tetracycline (Brand name: Tetracycline Capsule ) 500mg qid) for 10 days	Drug: Esomeprazole (BQ10); Nexium, esomeprazole, 40mg bid for 10 days; Other Names: Nexium (BQ10); Drug: dibismuth trioxide 120mg (BQ10); KCB F.C. TABLETS, dibismuth trioxide 120mg qid for 10 days; Other Names: KCB F.C. TABLETS; Drug: Metronidazole (BQ10); Flagyl, metronidazole 500mg tid for 10 days; Other Names: Flagyl; Drug: tetracycline (BQ10); Tetracycline (Brand name: Tetracycline Capsule ) 500mg qid for 10 days; Other Names: Tetracycline Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
eradication rate in the second-line treatment according to intention to treat (ITT) analysis	Urea breath test will be performed at least 6 weeks after the end of eradication therapy. Successful eradication of H. pylori will be defined as a negative 13C-UBT result. A positive 13C-UBT test will be defined as a delta value of 4 units or greater. All subjects will be asked to stop PPI and H2-blocker for at least two weeks before 13C-UBT.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse effects in the first line therapy in the two treatment groups	At enrollment, the patients will be informed of the common side effects from the studied drugs and they will be asked to record these symptoms during treatment. A standardized interview and questionnaire will be used to assess the adverse events	2 weeks
Eradication rates in the second line treatment according to per protocol (PP) analysis	Urea breath test will be performed at least 6 weeks after the end of eradication therapy. Patients not follow the protocol will be excluded for PP analysis.	6 weeks
Changes of gut microbiota in the two treatment groups	the stool specimens before, 2weeks after, 8 weeks after, and 1 year after the treatment will be collected for gut microbiota analysis	2 weeks, 8 weeks, and 1 year
Re-infection rate one year after eradication therapy	Urea breath test will be performed 1 year after the end of eradication therapy.	1 year

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Study Chair: Jyh-Ming Liou, MD, PhD, National Taiwan University Hospital; Principal Investigator: Yu-Jen Fang, MD, National Taiwan University Hospital, Yun-Lin Branch

Publications and helpful links

General Publications

• 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.
• Liou JM, Chen CC, Chen MJ, Chen CC, Chang CY, Fang YJ, Lee JY, Hsu SJ, Luo JC, Chang WH, Hsu YC, Tseng CH, Tseng PH, Wang HP, Yang UC, Shun CT, Lin JT, Lee YC, Wu MS; Taiwan Helicobacter Consortium. Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet. 2013 Jan 19;381(9862):205-13. doi: 10.1016/S0140-6736(12)61579-7. Epub 2012 Nov 16. Erratum In: Lancet. 2013 Apr 13;381(9874):1276.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: May 21, 2017
• First Submitted That Met QC Criteria: July 3, 2017
• First Posted (Actual): July 5, 2017

Study Record Updates

• Last Update Posted (Actual): June 4, 2018
• Last Update Submitted That Met QC Criteria: June 1, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Efficacy, Self
• Additional Relevant MeSH Terms: Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Helicobacter Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Metronidazole; Amoxicillin; Clarithromycin; Esomeprazole; Tetracycline
• Other Study ID Numbers: 201611053MINA

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No