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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Mahidol University
Sponsor:
Collaborator:
Takeda Pharmaceuticals International, Inc.
Information provided by (Responsible Party):
Monthira Maneerattanaporn, Mahidol University
ClinicalTrials.gov Identifier:
NCT01888237
First received: June 25, 2013
Last updated: June 27, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Dyspepsia
Helicobacter-associated Gastritis
Stomach Disorders
Drug: Double dose of PPI
Drug: sequence of drug use
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Mahidol University:

Primary Outcome Measures:
  • Eradication rate [ Time Frame: 4 weeks after the end of intervention ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Adherence rate/adverse events [ Time Frame: up to 2 weeks after intervention initiation ] [ Designated as safety issue: Yes ]
  • Prevalence of clarithromycin resistance HP [ Time Frame: 4 weeks after the end of intervention ] [ Designated as safety issue: No ]
  • Symptomatic responses regarding dyspeptic symptoms after HP eradication [ Time Frame: Baseline, week 4,8 and 24 after intervention completion ] [ Designated as safety issue: No ]

Estimated Enrollment: 118
Study Start Date: May 2013
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01888237

Contacts
Contact: Monthira Maneerattanaporn, MD., MS. 66816979551 monthira.man@mahidol.ac.th

Locations
Thailand
Division of gastroenterology, Department of Medicine, Siriraj hospital Recruiting
Bangkok Noi, Bangkok,, Thailand, 10700
Contact: Monthira Maneerattanaporn, MD., MS.    66816979551    monthira.man@mahidol.ac.th   
Principal Investigator: Monthira Maneerattanaporn, MD., MS.         
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

No publications provided

Responsible Party: Monthira Maneerattanaporn, Lecturer, Mahidol University
ClinicalTrials.gov Identifier: NCT01888237     History of Changes
Other Study ID Numbers: si111/2013
Study First Received: June 25, 2013
Last Updated: June 27, 2013
Health Authority: Thailand: Ethical Committee

Keywords provided by Mahidol University:
Dyspepsia
Helicobacter pylori
Clarithromycin resistance
Other Specified Disorders of Function of Stomach

Additional relevant MeSH terms:
Gastritis
Dyspepsia
Stomach Diseases
Signs and Symptoms, Digestive
Signs and Symptoms
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Clarithromycin
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014