High Dose PPI Triple Therapy Versus Sequential Therapy for Helicobacter Pylori Eradication

Dyspepsia Clinical Trial

Official title:

Randomized Open Labeled Clinical Trial: a Comparative Study of 10-day High Dose PPI-based Triple Therapy vs. 10-day Sequential Therapy for Helicobacter Pylori Eradication in Functional Dyspepsia Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01888237
• Other study ID #: si111/2013
• Status: Completed
• Phase: Phase 4
• First received: June 25, 2013
• Last updated: April 9, 2015
• Start date: May 2013
• Est. completion date: September 2014

Study information

• Verified date: April 2015
• Source: Mahidol University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Thailand: Ethical Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the efficacy between 1-day high dose PPI-based triple therapy vs. 10-day sequential therapy for Helicobacter pylori eradication in functional dyspepsia patients.

Description:

Background:

Helicobacter pylori (HP) play an important role in the pathogenesis of chronic gastritis, peptic ulcer diseases as well as gastric cancer. Helicobacter pylori eradication is a critical strategy to reduce aforementioned conditions. Proton-pump inhibitor (PPI)-based triple therapy (Standard dose PPIs+ Clarithromycin 1g/D + Amoxycillin 2g/D or Metronidazole 800 mg/D) is recommended as a frontline treatment in current guidelines for HP eradication, both from Thai and Second Asia-Pacific Consensus Guideline for H.pylori 2009. Unfortunately, it has been reported an unacceptably low eradication rate (<85%) of this regimen in a tertiary care hospital in Thailand. This occurrence is not surprised as the worldwide efficacy of this regimen had decreased to 50-75%. Of this, Clarithromycin resistance has been a major cause of the treatment failure.

Sequential therapy (ST) which consists of standard dose PPIs + amoxycillin 2 g/D for 5 days with 5 additional days of clarithromycin 1g/D + metronidazole 800 mg/D has been proposed to increase an efficacy in HP eradication. A recent meta-analysis of over three thousand population revealed a higher eradication rate over PPI-based triple therapy (TT). A consistent finding from Thailand was reported an impressive success rate of ST in HP eradication up to 95%. Therefore, more updated guidelines recommend using ST, not TT, as the first line regimen. However, ST is a complicated regimen for the patients to be followed. This might cause a low adherence rate in clinical practice as well as development of drug resistance in near future.

Interestingly, PPI is a pivotal in all regimens in HP eradication. There is evidence that the sustained higher intragastric pH is a major therapeutic determinant of HP eradication. Other factors including inflammatory cytokine polymorphisms, especially the IL-1B-511 T/T genotype and PPIs metabolizer, are the determinants of eradication by affecting gastric acid secretion and mucosal inflammation. Hence, higher dosage of PPIs is justified to eradicate HP. This has been shown in a recent meta-analysis that high dose PPI is better than standard dose PPI triple therapy in HP eradication of HP. Our study aims to compare the efficacy of ST to high dose PPI TT. Secondary outcomes include comparisons in the adherence and adverse events between both regimens, to determine the prevalence of clarithromycin resistance HP and determine improvement of dyspeptic symptoms after HP eradication

Primary Aim/Objective:

To evaluate eradication rates of Helicobacter pylori infection in functional dyspepsia patients amongst Thai population, compare between a 10-day sequential regimen (lansoprazole 30 mg b.d. plus amoxicillin 1000 mg b.d. for 5 days then lansoprazole 30 mg b.d., metronidazole 400 mg b.d. and clarithromycin 500 mg b.d. for the remaining 5 days) with a 10-day high dose PPI-based triple regimen (lansoprazole 60 mg b.d. plus clarithromycin 500 mg b.d. and amoxycillin 1000 mg b.d. for 10 days)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: September 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Functional dyspepsia patients (Rome III) with rapid urease test positive

• Age = 18 years old

• No history of HP eradication

Exclusion Criteria:

• Recent use of PPI, H2RA, NSAID, Antibiotics within 2 weeks

• Currently use of anticoagulants or ketoconazole

• C/I for gastric biopsy

• History of gastric surgery

• Comorbidity: ESRD, advanced cirrhosis, AIDS, stroke (bed ridden)

• Pregnancy or lactation

• Allergy to studied drugs

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dyspepsia
• Helicobacter-associated Gastritis
• Stomach Diseases
• Stomach Disorders

Intervention

Drug:
• Double dose of PPI
Lansoprasole (30mg) 2 tab oral BID
• sequence of drug use
lansoprazole 30 mg b.d. for 10 days amoxicillin 1000 mg b.d. (day 1 to day 5) metronidazole 400 mg b.d. (day 6-day 10) and clarithromycin 500 mg b.d. (day 6-day 10)

Locations

Country	Name	City	State
Thailand	Division of gastroenterology, Department of Medicine, Siriraj hospital	Bangkok Noi	Bangkok,

Sponsors (2)

Lead Sponsor	Collaborator
Mahidol University	Takeda Pharmaceuticals International, Inc.

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Eradication rate		4 weeks after the end of intervention	Yes
Secondary	Adherence rate/adverse events		up to 2 weeks after intervention initiation	Yes
Secondary	Prevalence of clarithromycin resistance HP		4 weeks after the end of intervention	No
Secondary	Symptomatic responses regarding dyspeptic symptoms after HP eradication		Baseline, week 4,8 and 24 after intervention completion	No