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

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

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.

Study Overview

• Status: Completed
• Conditions: Dyspepsia; Helicobacter-associated Gastritis; Stomach Disorders
• Intervention / Treatment: Drug: sequence of drug use; Drug: Double dose of PPI

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 Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Eradication rate	4 weeks after the end of intervention

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Mahidol University
• Collaborators: 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

Publications and helpful links

General Publications

• Auesomwang C, Maneerattanaporn M, Chey WD, Kiratisin P, Leelakusolwong S, Tanwandee T. Ten-day high-dose proton pump inhibitor triple therapy versus sequential therapy for Helicobacter pylori eradication. J Gastroenterol Hepatol. 2018 Nov;33(11):1822-1828. doi: 10.1111/jgh.14292. Epub 2018 Jun 27.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (ACTUAL): August 1, 2014
• Study Completion (ACTUAL): September 1, 2014

Study Registration Dates

• First Submitted: June 25, 2013
• First Submitted That Met QC Criteria: June 26, 2013
• First Posted (ESTIMATE): June 27, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): April 10, 2015
• Last Update Submitted That Met QC Criteria: April 9, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Helicobacter pylori; Dyspepsia; Clarithromycin resistance; Other Specified Disorders of Function of Stomach
• Additional Relevant MeSH Terms: Digestive System Diseases; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Gastritis; Dyspepsia
• Other Study ID Numbers: si111/2013