Comparison of the Levofloxacin Sequential Therapy and Quadruple Therapy in Second Line Treatment for HP

NCT03148366 | Completed Phase 3 DMC

• 1 other identifier: 201410001MINC
• Study Type: interventional
• Target: 560
• Locations: 1 country
• Sites: 2

Brief Summary

Objectives: Eradication of H. pylori infection could reduce the occurence or recurrence of gastric cancer and peptic ulcer diseases. However, it was estimated that 15-20% of patients would fail from first line standard eradication therapy and need second line rescue therapy. About 15-30% of patient would fail from second line therapy. Bismuth quadruple therapy and triple therapy containing levofloxacin are currently the recommended rescue therapies in the second line and third line treatment. Recently, our pilot study showed that modified sequential therapy containing levofloxacin achieved high eradication rate (95%) in the second line therapy. The regimen includes a PPI plus amoxicillin for 5-7 days, followed by a PPI plus levofloxacin and metronidazole for another 5-7 days. However, whether this modified sequential therapy containing levofloxacin is more effective than bismuth quadruple therapy in the second line and third line treatment remains unknown. Besides, the impact of these regimens on the antibiotic resistance , microbiota of gut flora, and metabolic factors remains unknown. Aims: Therefore, the investigators aimed to

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

Conditions

Helicobacter

Keywords

Self Efficacy

Outcome Measures

Primary Outcomes (1)

• Eradication rate after second line eradication therapy according to ITT analysis

  The eradication status will be determined by urea breath test (UBT) at least 6 weeks after completion of the treatment. The delta value of UBT of 4 or less will be defined as negative and successful eradication.

  6 weeks after completion of treatment

Secondary Outcomes (3)

• Adverse effects during eradication therapy

  during treatment (2 weeks)

• Long term eradication rate 1 year after eradication therapy

  1 year after treatment

• changes of gut microbiota before and after eradication therapy

  1 year

Study Arms (2)

Levofloxacin based sequential therapy

EXPERIMENTAL

Levofloxacin based sequential therapy : sequential therapy containing levofloxacin for 14 days D1-D7: (esomeprazole 40mg bid + amoxicillin 1gm bid) for 7 days D8-D14: (esomeprazole 40mg bid + levofloxacin 250mg bid + metronidazole 500mg bid) for another 7 days

Drug: Levofloxacin based sequential therapy

bismuth quadruple therapy (BQ)

ACTIVE COMPARATOR

bismuth quadruple therapy for 10 days (BQ) D1-D10: (esomeprazole 40mg bid + Dibismuth trioxide 120mg qid + metronidazole 500mg tid + tetracycline 500mg qid) for 10 days

Drug: bismuth quadruple therapy for 10 days (BQ)

Interventions

Levofloxacin based sequential therapy DRUG

D1-D7: (esomeprazole 40mg bid + amoxicillin 1gm bid) for 7 days D8-D14: (esomeprazole 40mg bid + levofloxacin 250mg bid + metronidazole 500mg bid) for another 7 days

Levofloxacin based sequential therapy

bismuth quadruple therapy for 10 days (BQ) DRUG

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

bismuth quadruple therapy (BQ)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (2)

National Taiwan University Hospital

Taipei, Taiwan

Location

National Taiwan University Hospital, Yunlin branch

Yunlin, Taiwan

Location

Related Publications (4)

• 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.

  PMID: 23158886 RESULT

• Liou JM, Chen CC, Chang CY, Chen MJ, Fang YJ, Lee JY, Chen CC, Hsu SJ, Hsu YC, Tseng CH, Tseng PH, Chang L, Chang WH, Wang HP, Shun CT, Wu JY, Lee YC, Lin JT, Wu MS; Taiwan Helicobacter Consortium. Efficacy of genotypic resistance-guided sequential therapy in the third-line treatment of refractory Helicobacter pylori infection: a multicentre clinical trial. J Antimicrob Chemother. 2013 Feb;68(2):450-6. doi: 10.1093/jac/dks407. Epub 2012 Oct 25.

  PMID: 23099849 RESULT

• Liou JM, Chen CC, Chen MJ, Chang CY, Fang YJ, Lee JY, Sheng WH, Wang HP, Wu MS, Lin JT. Empirical modified sequential therapy containing levofloxacin and high-dose esomeprazole in second-line therapy for Helicobacter pylori infection: a multicentre clinical trial. J Antimicrob Chemother. 2011 Aug;66(8):1847-52. doi: 10.1093/jac/dkr217. Epub 2011 May 31.

  PMID: 21632579 RESULT

• Liou JM, Jiang XT, Chen CC, Luo JC, Bair MJ, Chen PY, Chou CK, Fang YJ, Chen MJ, Chen CC, Lee JY, Yang TH, Yu CC, Kuo CC, Chiu MC, Chen CY, Shun CT, Hu WH, Tsai MH, Hsu YC, Tseng CH, Chang CY, Lin JT, El-Omar EM, Wu MS; Taiwan Gastrointestinal Disease and Helicobacter Consortium. Second-line levofloxacin-based quadruple therapy versus bismuth-based quadruple therapy for Helicobacter pylori eradication and long-term changes to the gut microbiota and antibiotic resistome: a multicentre, open-label, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023 Mar;8(3):228-241. doi: 10.1016/S2468-1253(22)00384-3. Epub 2022 Dec 19.

  PMID: 36549320 DERIVED

Study Officials

• Ming-Shiang Wu

  National Taiwan University Hospital

  STUDY CHAIR

• Jyh-Ming Liou

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2015
• First Posted: May 11, 2017
• Study Start: February 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2020
• Last Updated: June 8, 2022

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

TW (2)