Increased Re-eradication Rate of Helicobacter Pylori by Adding N-acetylcystein or Metronidazole to the Triple Therapy

Increased Second-line Eradication Rate of Helicobacter Pylori by Adding N-acetylcystein or Metronidazole to the Conventional Triple Therapy.

Compare efficacy and safety of 10-day triple therapy (rabeprazole, clarithromycin and amoxicillin) plus N-acetylcystein versus 10-day concomitant therapy (rabeprazole, clarithromycin, amoxicillin and metronidazole) for re-eradication for gastric Helicobacter pylori infection.

Study Overview

• Status: Unknown
• Conditions: Bacterial Infection Due to Helicobacter Pylori (H. Pylori)
• Intervention / Treatment: Drug: 10RAC+acetylcystein; Drug: 10RAC+metronidazole

Detailed Description

Background: Antimicrobial resistance has decreased the eradication rates of common used triple therapy for Helicobacter pylori infection (less than 80%). Such treatment for patient previously with treatment failure, the retreatment eradication rate is less then 50%. Some studies showed the Helicobacter pylori form biofilm to prevent entry of antibiotics, and the N-acetylcystein is helpful to dissolve the biofilm.

Objective: To determine the eradication rate of the common used triple therapy after adding N-acetylcystein for second line treatment for adults infected with Helicobacter pylori in Eastern Taiwan.

Design: Randomized, open-label, prospective controlled trial.

Patients: who are previously failed the primary treatment for eradication and still infected by Helicobacter pylori.

Measurements: 13C-urea breath test, upper endoscopy, histologic evaluation, rapid urease test, bacterial culture, assessment of antibiotic resistance and CYP2C19 genotype of host.

Intervention: patients with Helicobacter pylori eradication treatment failure are recruited and randomly assigned to receive one of the following therapeutic schemes: 1) study group: rabeprazole 20mg bid + amoxicillin 1g bid + clarithromycin 0.5g bid + N-acetylcystein 0.6g bid for 10 days; 2) control group: rabeprazole 20mg bid + amoxicillin 1g bid + clarithromycin 0.5g bid + metronidazole 0.5g bid for 10 days. Repeat upper endoscopy for histologic evaluation, rapid urease test or 13C-urea breath test after 4 week of treatment to assess the treatment result. The influence on the hybrid therapies of antibiotic resistance of Helicobacter pylori and CYP2C19 genotype of host were determined.

Expected results: The new second line treatment for eradication of Helicobacter pylori is effective, and to determine the relation of antibiotic resistance of Helicobacter pylori and CYP2C19 genotype of host to the treatment result.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Hualien, Taiwan, 97002
    • Recruiting
    • Buddhist Tzu Chi General Hospital
    • Contact: Ming-Cheh CHEN, MD; Phone Number: +886-910-521003; Email: MingCheh_chen@tzuchi.com.tw
    • Principal Investigator: Chi-Tan HU, PhD, MD
    • Sub-Investigator: Wei-Yi RAY, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient after treatment for Helicobacter pylori eradication.
• Still clinically with evidence of gastric Helicobacter pylori infection.

Exclusion Criteria:

• woman in breast feeding or pregnancy.
• allergy to drugs used in study.
• never treated for H. pylori.
• intolerance to fructose, lactose.
• patients with hematologic, brain or spinal disorders.
• patients under 20 years old.
• patients with malignancy or with decompensated function of vital organs.

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: Acetylcystein; 10-day triple therapy plus N-acetyl-cystein to remove the biofilm.	Drug: 10RAC+acetylcystein; 10-days rabeprazole 20mg b.i.d + clarithromycin 500mg b.i.d + amoxicillin 1000mg b.i.d + N-acetyl-cystein 600mg b.i.d; Other Names: Klaricid; Fluimucil; Pariet; Hiconcil
ACTIVE_COMPARATOR: Metronidazole; 10-day triple therapy plus metronidazole (concomitant therapy) as active comparator	Drug: 10RAC+metronidazole; 10-days rabeprazole 20mg b.i.d + clarithromycin 500mg b.i.d + amoxicillin 1000mg b.i.d + metronidazole 500mg b.i.d; Other Names: Klaricid; Flagyl; Pariet; Hiconcil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Re-eradication rate	A negative post-treatment 13C-urea breath test result at more than 4 weeks after complete use of drug for treatment.	4 weeks after complete use of drug for treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Influence of Participant's CYP2C19 genotype on re-eradication rate	Influence of Participant's CYP2C19 genotype (EM, IM or PM) on re-eradication rate of Helicobacter pylori	4 weeks after complete use of drug for treatment

Collaborators and Investigators

• Sponsor: Buddhist Tzu Chi General Hospital

Publications and helpful links

General Publications

• Wu DC, Hsu PI, Wu JY, Opekun AR, Kuo CH, Wu IC, Wang SS, Chen A, Hung WC, Graham DY. Sequential and concomitant therapy with four drugs is equally effective for eradication of H pylori infection. Clin Gastroenterol Hepatol. 2010 Jan;8(1):36-41.e1. doi: 10.1016/j.cgh.2009.09.030. Epub 2009 Oct 3.
• Cammarota G, Branca G, Ardito F, Sanguinetti M, Ianiro G, Cianci R, Torelli R, Masala G, Gasbarrini A, Fadda G, Landolfi R, Gasbarrini G. Biofilm demolition and antibiotic treatment to eradicate resistant Helicobacter pylori: a clinical trial. Clin Gastroenterol Hepatol. 2010 Sep;8(9):817-820.e3. doi: 10.1016/j.cgh.2010.05.006. Epub 2010 May 31.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (ANTICIPATED): December 1, 2012
• Study Completion (ANTICIPATED): December 1, 2012

Study Registration Dates

• First Submitted: April 4, 2012
• First Submitted That Met QC Criteria: April 5, 2012
• First Posted (ESTIMATE): April 6, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): April 6, 2012
• Last Update Submitted That Met QC Criteria: April 5, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Helicobacter pylori; antibiotic resistance; biofilm; N-acetylcystein; second-line eradication treatment
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Gastrointestinal Agents; Protective Agents; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Respiratory System Agents; Antiprotozoal Agents; Antiparasitic Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Antioxidants; Free Radical Scavengers; Expectorants; Metronidazole; Rabeprazole; Clarithromycin; Acetylcysteine
• Other Study ID Numbers: IRB100-26