Sequential Versus Quadruple Therapy in the Second-line Treatment

Phase 4

• Conditions: Helicobacter Pylori Infection
• Interventions: Drug: Esomeprazole (S14); Drug: Esomeprazole (BQ10); Drug: Amoxicillin (ST14); Drug: dibismuth trioxide 120mg (BQ10); Drug: Metronidazole (BQ10); Drug: Clarithromycin (ST14); Drug: tetracycline (BQ10); Drug: Metronidazole (ST14)

• Registration Number: NCT03208426
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

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.

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 Timeline

• Study First Submitted: 2017-05-21
• Study First Submitted QC: 2017-07-03
• Study First Posted: 2017-07-05
• Study Start: 2017-10-01
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-01
• Last Update Posted: 2018-06-04
• Primary Completion: 2019-12-31
• Study Completion: 2020-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 240

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
bismuth quadruple therapy for 10 days	tetracycline (BQ10)	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
Sequential therapy for 14 days	Amoxicillin (ST14)	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
bismuth quadruple therapy for 10 days	Metronidazole (BQ10)	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
Sequential therapy for 14 days	Esomeprazole (S14)	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
bismuth quadruple therapy for 10 days	Esomeprazole (BQ10)	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
Sequential therapy for 14 days	Clarithromycin (ST14)	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
Sequential therapy for 14 days	Metronidazole (ST14)	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
bismuth quadruple therapy for 10 days	dibismuth trioxide 120mg (BQ10)	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

Primary Outcome Measures

Name	Time	Method
eradication rate in the second-line treatment according to intention to treat (ITT) analysis	6 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Eradication rates in the second line treatment according to per protocol (PP) analysis	6 weeks	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.
Changes of gut microbiota in the two treatment groups	2 weeks, 8 weeks, and 1 year	the stool specimens before, 2weeks after, 8 weeks after, and 1 year after the treatment will be collected for gut microbiota analysis
Re-infection rate one year after eradication therapy	1 year	Urea breath test will be performed 1 year after the end of eradication therapy.
Incidence of adverse effects in the first line therapy in the two treatment groups	2 weeks	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

Trial Locations

Locations (1)

Jyh-Ming Liou; 🇨🇳 Taipei, Taiwan, Taiwan