Clinical trial NCT01042184: Efficacy of 10-day and 14-day Sequential Therapy Versus Triple Therapy on the Eradication of Helicobacter Pylori
Official title: Phase IV Study Comparing the Duration of Sequential Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: H. Pylori Infection
Keywords: H. pylori infected patients without prior eradication therapy
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2010-01-05
Enrollment: 900
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background: Helicobacter pylori infection has been shown to be associated with the development of gastric cancer and peptic ulcer diseases. Eradication of H. pylori infection could reduce the occurence or recurrence of these diseases. However, the eradication rate of clarithromycin-based triple therapy has been declining in recent years, probably related to the increasing resistant rate to clarithromycin. 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 and need to be rescued with third line therapy. In recent years, the concept of sequential therapy has been advocated in the treatment of H. pylori infection. The regimen includes a PPI plus amoxicillin for five days, followed by a PPI plus clarithromycin and tinidazole for another five days. The eradication rate in the first line treatment of sequential therapy had been reported to be as high as 90%. More importantly, it has been demonstrated that the eradication rate among patients with clarithromycin-resistant strains could be as high as 89%. However, tinidazole is not available in many countries. Whether metronidazole would be an effective alternative to tinidazole in the sequential therapy remains unknown. Besides, whether extending the duration of sequential therapy from 10-day to 14-day would result in higher eradication rate also deserves further investigation. Furthermore, data on the efficacy of rescue regimens for patients who failed from first line sequential therapy are also lacking. The impact of clarithromycin, metronidazole resistance and CYP2C19 polymorphism on the sequential therapy containing metronidazole (rather than tinidazole) also has not been reported.

Aims: Therefore, we aim to assess

1. whether the substitution of metronidazole for tinidazole in the sequential therapy is also more effective than clarithromycin-based triple therapy
2. whether extending the duration of sequential therapy from 10-day to 14-day would achieve higher eradication rate
3. whether levofloxacin-based sequential therapy for 14-days is effective as second line rescue regimen for those who failed from first line sequential therapy
4. the impact of antibiotic resistance and CYP2C19 polymorphism on the eradication rate of sequential therapy


Eligibility criteria: Inclusion Criteria:

1. Patients are 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 enrollment.

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 (amoxicillin, clarithromycin, levofloxacin, metronidazole) and prompt pump inhibitors (lansoprazole),
5. contraindication to treatment drugs,
6. pregnant or lactating women,
7. severe concurrent disease,
8. Patients who cannot give informed consent by himself or herself.

Primary outcomes:
measure: Eradication rate according to Intention to treat (ITT) and per-protocol (PP) analysis
timeFrame: 6 weeks after eradication therapy
Secondary outcomes:
measure: The impact of antibiotic resistance and CYP2C19 polymorphism on the eradication rate of sequential therapy
timeFrame: 6 weeks after eradication therapy
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Jyh-Ming Liou, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.