Triple Therapy Versus Levofloxacin-based Therapy for Helicobacter Pylori Eradication in Mexico.
Condition: Helicobacter Pylori Gastritis
MeSH terms: Gastritis
Study type: Interventional
Phase: Phase 3

Summary: 
      The goal of this trial is to compare the non-inferiority efficacy and safety of two different
      treatment schemes: pantoprazole 80 mg + levofloxacin 500 mg + azithromycin 500 mg once daily
      (PLA, test) vs. clarithromycin 500 mg + lansoprazole 30 mg + amoxicillin 1 g twice daily
      (CLA, reference), each during 10 days, over Helicobacter Pylori (HP) eradication. Both
      schemes will be tested in treatment-naive patients, with biopsy-based diagnosis for HP
      infection. One month after finishing each treatment, C13-urea breath testing will be required
      to verify HP eradication. Biopsies will also be taken to identify Clarithromycin-resistance
      mutations in HP strains by fluorescence in situ hybridization (FISH).
    

Detailed description: 
      This phase IIIb study is a prospective, open-label, randomized, parallel-group,
      non-inferiority efficacy and safety trial. It will be carried out at four outpatient clinics
      in two cities placed in Mexico (Mexico City and the town of Toluca). The study was approved
      by a central Ethics Committee and by COFEPRIS (Mexican Federal Commission for Sanitary Risks
      Protection) and will be conducted in accordance with Helsinki Declaration for the protection
      of human subjects and with Good Clinical Practice guidelines.

      Two hundred and thirty subjects aged 18 to 65 years, with HP infection proven by endoscopic
      biopsy and treatment-naïve will be included in the study after signing the informed consent.
      They will be randomly allocated into one of two groups: Group 1 will receive clarithromycin
      500 mg twice daily (bid), amoxicillin 1 g bid, and lansoprazole 30 mg bid (Pylopac®, Medix SA
      de CV, Mexico); Group 2 will receive azithromycin 500 mg once daily (od) (Truxa®,
      Laboratorios Monte Verde SA, Argentina), levofloxacin 500 mg od (Laboratorios Asofarma de
      México SA de CV, Mexico), and pantoprazole 80 mg od (Zoltum®, Laboratorio Monte Verde SA,
      Argentina). Both groups will receive the treatment for 10 days. Antibiotics will be
      prescribed after meals, whereas the proton-pump inhibitor will be taken in a fasting
      condition. No other medication will be allowed until the end of the treatment.

      Subjects will be evaluated using the 13C-urea breath test (13C-UBT) four weeks after HP
      eradication treatment. Eradication of H. pylori will be defined as a negative 13C-UBT. No
      further medication will be allowed during the four weeks preceding the 13C-UBT.

      Regarding safety assessment, blood samples will be collected in a central laboratory
      following signature of the informed consent and before treatment beginning. An additional
      blood sample will be drawn at the end of treatment of each group for comparison with initial
      results. Patient compliance and treatment-related AEs will be assessed at the end of the
      treatment (except whether the AE is serious, in which case it will be reported immediately
      and appropriate actions will be decided at that time).

      All biopsies will be reviewed by a central pathologist. Endoscopic biopsies will be
      immediately fixed in 10% buffer formalin, embedded in paraffin, sectioned (4 mm slice
      thickness), and dehydrated in a series of increasing ethanol/xylol concentration. Each
      section will be stained with hematoxylin and eosin (H&E). The diagnosis of gastritis will be
      established in accordance with the updated Sydney system10. Fluorescent in situ hybridization
      (FISH) will be performed in all biopsies. Briefly, formalin-fixed paraffin-embedded 4-mm
      tissue sections will be spotted onto slides coated with poly-L-lysine and processed by hexane
      and ethanol. Hybridization will be done using the commercially available BACTfish H pylori
      combi kit (Izinta Trading Co. Ltd., Hungary). The probe for H. pylori identification (Hpy 1)
      (5'CACACCTGACTGACTATCCCG-3') will be labeled with fluorescein isothiocyanate (FITC) that
      provides a green signal, and the probes that detect the three most prevalent
      clarithromycin-resistance mutations (ClaR1 (A2143G) 5'CGGGGTCTTCCCGTCTt-3', ClaR2 (A2144G)
      5'CGGGGCTCTCCGTCTT-3', and ClaR3 (A21443C) 5-CGGGGTCTTGCCGTCTT-3') will be labeled with red
      fluorochrome (Cy3). Following hybridization for 90 minutes at 46 °C, sections will be washed
      with wash buffer twice at 46 °C for 15 minutes. Air-dried sections will be stained with 4',
      6' diamino-2-phenylindole (DAPI). Slides will be evaluated using fluorescence Nikon Eclipse
      80i microscope. Pictures will be taken with a Nikon DS-Fi1 camera and processed with
      NIS-Elements 2.1 software.

      Continuous variables will be described using means and standard deviation. Efficacy analysis
      will be based on H. pylori eradication rate in subjects that finished treatment as per
      protocol. Considering a non-inferiority approach, Group 2 will be considered not inferior to
      Group 1 if the upper limit of the 95% confidence interval (CI) for the difference in the
      eradication rate between both groups is lower than the pre-established non-inferiority margin
      δ = 0.12%. Such margin was selected in accordance with previously published trials performed
      with the reference combination.

      Chi-square test and Student's t-test will be used to compare both groups regarding baseline
      data, eradication rate, adverse events and biochemical results for safety analysis. P value <
      0.05 will be considered significant. IBM SPSS 21 will be used to perform the statistical
      analysis.
    

Intervention name(s): CLA (Clarithro+Lanso+Amoxi); PLA (Panto+Levoflox+Azithro)
Intervention type(s): Drug; Drug
Intervention description(s): Tablets of oral administration administered to subjects randomized to this group twice daily for 10 days.; Tablets of oral administration to subjects randomized to this group once daily for 10 days.
Other intervention name(s): Pylopac®, Medix, Mexico; Zoltum®, Truxa® (MTV SA, Argentina), Levofloxacino, AsoMex
Intervention MeSH terms: Ofloxacin; Levofloxacin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Helicobacter Pylory infections; Levofloxacin; Antibiotic resistance; Clarithromycin; Mutations; Fluorescence; Hybridization