Genotypic Resistance-guided Versus Empirical Therapy for H. Pylori Eradication.

Genotypic Resistance-guided Triple Therapy Versus Empirical Concomitant Therapy for First-line H. Pylori Eradication.

This study aims to investigate the efficacy of a 7-day genotypic resistance-guided triple therapy, compared with empirical concomitant therapy, for first-line eradication of H. pylori.

Study Overview

• Status: Unknown
• Conditions: Helicobacter Pylori Infection
• Intervention / Treatment: Drug: Esomeprazole 40mg; Drug: Clarithromycin 500mg; Drug: Amoxicillin 1000 MG; Drug: Levofloxacin 500mg; Drug: Rifabutin 150 MG; Drug: Metronidazole 500 mg

Detailed Description

Empiric eradication of H. pylori becomes steadily more challenging because of increasing antibiotic resistance. In high-resistance countries where bismuth and/or tetracycline are unavailable (eg; Greece), non-bismuth quadruple therapies are currently recommended as first-line therapeutic options; however, eradication rates >95% are infrequently achieved and even >90% are disputed. Antimicrobial susceptibility-guided therapy is a promising alternative in order to maintain high therapeutic efficacy. However, traditional culture-based susceptibility testing methods have several shortcomings, including they are time-consuming and they do not 100% reflect in vivo eradication. Recent guidelines also recommend the use of molecular testing for evaluation of H. pylori antibiotic susceptibility. Nevertheless, the efficacy of genotypic resistance-guided treatment of H. pylori has been seldom appraised. Therefore, the investigators conducted this prospective randomized controlled trial aiming to investigate the efficacy of a 7-day genotypic resistance-guided triple therapy, compared with empirical concomitant therapy, for first-line eradication of H. pylori.

• Study Type: Interventional
• Enrollment (Anticipated): 304
• Phase: Phase 4

Contacts and Locations

Study Locations

• Greece
  • Nea Ionia
    • Athens, Nea Ionia, Greece, 14233
      • Recruiting
      • Konstantopoulio-Patision General Hospital
      • Contact: Vasilios Papastergiou, MD; Phone Number: +302132057018; Email: gastrenterologiki@konstantopouleio.gr

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:

• Consecutive outpatients aged ≥18 years with documented H. pylori infection. Mental and legal ability to provide written informed consent.

Exclusion Criteria:

• previous history of H. pylori eradication therapy
• history of allergies to the medications used
• previous esophageal or gastric surgery
• serious systemic disease
• pregnancy or lactation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Genotypic resistance-guided triple therapy; In the group of genotypic resistance-guided triple therapy, a molecular assay based on DNA-strip technology was used to determine the genotypic resistance of H. Pylori to clarithromycin (23SrRNA mutations) and fluoroquinolones (gyrA mutations) from gastric biopsy specimens. According to 23SrRNA and gyrA mutational analyses, a 7-day tailored triple therapy therapy was given as follows: Wild-type 23SrRNA: Clarithromycin-based triple therapy comprising esomeprazole 40 mg b.i.d., amoxicillin 1 g b.i.d. and clarithromycin 500 mg b.i.d. 23SrRNA mutated/wild-type gyrA: Levofloxacin-based triple therapy comprising esomeprazole 40 mg b.i.d., amoxicillin 1 g b.i.d. and levofloxacin 500 mg b.i.d. 23SrRNA mutated/gyrA mutated: Rifabutin-based triple therapy comprising esomeprazole 40 mg b.i.d., amoxicillin 1 g t.i.d. and rifabutin 150 mg b.i.d.	Drug: Esomeprazole 40mg; Use in a drug combination for H. pylori eradication; Drug: Clarithromycin 500mg; Use in a drug combination for H. pylori eradication; Drug: Amoxicillin 1000 MG; Use in a drug combination for H. pylori eradication; Drug: Levofloxacin 500mg; Use in a drug combination for H. pylori eradication; Drug: Rifabutin 150 MG; Use in a drug combination for H. pylori eradication
ACTIVE_COMPARATOR: Empirical concomitant therapy; In the empirical concomitant group, patients received esomeprazole 40mg, amoxicillin 1gr, clarithromycin 500mg and metronidazole 500mg, all b.i.d., for 10-14 days.	Drug: Esomeprazole 40mg; Use in a drug combination for H. pylori eradication; Drug: Clarithromycin 500mg; Use in a drug combination for H. pylori eradication; Drug: Amoxicillin 1000 MG; Use in a drug combination for H. pylori eradication; Drug: Metronidazole 500 mg; Use in a drug combination for H. pylori eradication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of H. pylori eradication	Rate of H. pylori eradication by intention to treat/per protocol in each group at least 6 weeks after treatment completion using the urea breath test.	At least 6 weeks after treatment completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of adverse effects	Adverse events were investigated by means of a structured clinical interview immediately after the completion of therapy. The subjects were asked to grade the severity of adverse events according to their influence on daily activities, experienced as "mild" (transient and well tolerated), "moderate" (causing discomfort and partially interfering with daily activities), or "severe" (causing considerable interference with daily activities).	At least 6 weeks after treatment completion
Compliance rates	Drug compliance was determined by counting unused medication. For this purpose, any tablet that was not consumed was brought back to the clinic for pill count. Poor compliance was defined as taking less than 80% of the total medication prescribed.	At least 6 weeks after treatment completion

Collaborators and Investigators

• Sponsor: Konstantopoulio-Patission General Hospital of Nea Ionia

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2019
• Primary Completion (ANTICIPATED): February 28, 2020
• Study Completion (ANTICIPATED): February 28, 2020

Study Registration Dates

• First Submitted: September 12, 2019
• First Submitted That Met QC Criteria: September 12, 2019
• First Posted (ACTUAL): September 16, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 19, 2019
• Last Update Submitted That Met QC Criteria: September 17, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: H. pylori; tailored therapy; genotypic resistance; concomitant therapy
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Gastrointestinal Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Metronidazole; Rifabutin; Amoxicillin; Clarithromycin; Levofloxacin; Ofloxacin; Esomeprazole
• Other Study ID Numbers: 10548 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No