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

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	Phase
Dyspepsia; Helicobacter-associated Gastritis; Stomach Disorders	Drug: Double dose of PPI; Drug: sequence of drug use	Phase 4

Detailed 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)

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	118 participants
Allocation:	Randomized
Intervention Model:	Factorial Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Study Start Date :	May 2013
Actual Primary Completion Date :	August 2014
Actual Study Completion Date :	September 2014

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: Sequential therapy (ST); 10 day Sequential therapy: 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	Drug: 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)
Experimental: High dose PPI triple therapy(TT); 10 day high dose PPI triple therapy: lansoprazole 60 mg b.d. plus clarithromycin 500 mg b.d. and amoxycillin 1000 mg b.d. for 10 days	Drug: Double dose of PPI; Lansoprasole (30mg) 2 tab oral BID

Outcome Measures

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Primary Outcome Measures :

1. Eradication rate [ Time Frame: 4 weeks after the end of intervention ]

Secondary Outcome Measures :

1. Adherence rate/adverse events [ Time Frame: up to 2 weeks after intervention initiation ]
2. Prevalence of clarithromycin resistance HP [ Time Frame: 4 weeks after the end of intervention ]
3. Symptomatic responses regarding dyspeptic symptoms after HP eradication [ Time Frame: Baseline, week 4,8 and 24 after intervention completion ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

Thailand
Division of gastroenterology, Department of Medicine, Siriraj hospital
Bangkok Noi, Bangkok,, Thailand, 10700

Sponsors and Collaborators

Mahidol University

Takeda Pharmaceuticals International, Inc.

Investigators

Principal Investigator:	monthira maneerattanaporn	Division of gastroenterology, Department of Medicine, Siriraj hospital 2, Pran-nok, Bangkoknoi, Bangkok, Thailand, Mahidol University

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Monthira Maneerattanaporn, Lecturer, Mahidol University
ClinicalTrials.gov Identifier:	NCT01888237 History of Changes
Other Study ID Numbers:	si111/2013
First Posted:	June 27, 2013
Last Update Posted:	April 10, 2015
Last Verified:	April 2015

Keywords provided by Monthira Maneerattanaporn, Mahidol University:

Dyspepsia; Helicobacter pylori; Clarithromycin resistance; Other Specified Disorders of Function of Stomach

Additional relevant MeSH terms:

Dyspepsia; Gastritis; Stomach Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Amoxicillin; Clarithromycin; Lansoprazole	Anti-Bacterial Agents; Anti-Infective Agents; Protein Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Anti-Ulcer Agents; Gastrointestinal Agents; Proton Pump Inhibitors