Clinical trial NCT01888237: High Dose PPI Triple Therapy Versus Sequential Therapy for Helicobacter Pylori Eradication
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Dyspepsia
Helicobacter-associated Gastritis
Stomach Disorders
Keywords: Dyspepsia
Helicobacter pylori
Clarithromycin resistance
Other Specified Disorders of Function of Stomach
Lead sponsor: Mahidol University
Sponsor class: OTHER
Collaborators: name: Takeda Pharmaceuticals International, Inc.
First posted: 2013-06-27
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Eradication rate
timeFrame: 4 weeks after the end of intervention
Secondary outcomes:
measure: Adherence rate/adverse events
timeFrame: up to 2 weeks after intervention initiation
measure: Prevalence of clarithromycin resistance HP
timeFrame: 4 weeks after the end of intervention
measure: Symptomatic responses regarding dyspeptic symptoms after HP eradication
timeFrame: Baseline, week 4,8 and 24 after intervention completion
Other outcomes:
Locations:
city: Bangkok Noi
country: Thailand
facility: Division of gastroenterology, Department of Medicine, Siriraj hospital
state: Bangkok,
Study officials:
affiliation: Division of gastroenterology, Department of Medicine, Siriraj hospital 2, Pran-nok, Bangkoknoi, Bangkok, Thailand, Mahidol University
name: monthira maneerattanaporn
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.