Triple Therapy Versus Levofloxacin-based Therapy for Helicobacter Pylori Eradication in Mexico.

March 31, 2016 updated by: Asofarma de México S.A de C.V.

Helicobacter Pylori Eradication in Mexico With a Levofloxacin-containing Scheme Versus Clarithromycin-based Triple Therapy: a Randomized, Open-label, Non-inferiority, Phase 3b Trial.

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

230

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female adult subjects who wish to participate after signing the informed consent.
  2. Aged between 18 and 65 years.
  3. HP infection diagnosed by endoscopic gastric biopsy.

  4. Subjects who fulfill the following HP eradication criteria according to Maastricht 3 Consensus Report:

    • Non ulcer dyspepsia with gastric biopsy positive for HP infection,
    • Uncomplicated duodenal ulcer (without active bleeding, perforation or stenosis) with gastric biopsy positive for HP infection,
    • Uncomplicated benign gastric ulcer (without active bleeding, perforation or stenosis) with gastric biopsy positive for HP infection,
    • Chronic intake of NSAIDs with gastric biopsy positive for HP infection without active gastrointestinal bleeding.

Exclusion Criteria:

  1. Pregnant or lactating women.
  2. Subjects who have previously received the PLA or CLA treatment.
  3. Subjects who are diagnosed by endoscopy with upper gastrointestinal bleeding secondary to active peptic ulcer (gastric or duodenal) with injuries classified in any of the following stages of the Forrest Classification: I-a (Spurting hemorrhage), I-b (Oozing hemorrhage), II-a (Visible vessel) or II-b (Adherent clot).
  4. Subjects who are diagnosed by endoscopy with upper gastrointestinal bleeding by erosive gastritis secondary to active NSAID with positive biopsy for HP infection and whose clinical conditions require hospitalization and / or blood transfusion.
  5. Subjects with psychiatric disorders including eating disorders.
  6. Subjects with chronic degenerative diseases including uncontrolled hepatic, renal or endocrine diseases (except diabetes controlled by oral hypoglycemic agents or controlled hypothyroidism), malabsorption or chronic diarrhea, history of seizures or epilepsy, gastric surgery or subjects with oncological diseases.
  7. Subjects with previous allergic reactions to any of the treatment components: Pantoprazole, Amoxicillin, Clarithromycin, Azithromycin or Levofloxacin.
  8. Subjects with a history of photosensitivity or tendinitis secondary to quinolones intake.

  9. Subjects who are taking any of the following medications:

    • NSAIDS: Fenbufen
    • ergot
    • Oral anticoagulants
    • Cyclosporine
    • Digoxin

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: CLA (Clarithro+Lanso+Amoxi)
Clarithromycin 500 mg bid, Lansoprazole 30 mg bid and Amoxicillin 500 bid, tablets of oral administration, during 10 days.
Drug: CLA (Clarithro+Lanso+Amoxi)
Tablets of oral administration administered to subjects randomized to this group twice daily for 10 days.
Other Names:
  • Pylopac®, Medix, Mexico
Experimental: PLA (Panto+Levoflox+Azithro)
Pantoprazole 80 mg od, Levofloxacin 500 mg od and Azithromycin 500 mg od, tablets of oral administration, during 10 days.
Drug: PLA (Panto+Levoflox+Azithro)
Tablets of oral administration to subjects randomized to this group once daily for 10 days.
Other Names:
  • Zoltum®, Truxa® (MTV SA, Argentina), Levofloxacino, AsoMex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
HP eradication rate calculated from negative 13C-urea breath tests.
Time Frame: Four weeks after the end of the allocated treatment.
Four weeks after the end of the allocated treatment.

Secondary Outcome Measures

Outcome Measure
Time Frame
Determine the frequency of Clarithromycin-resistance mutations by fluorescence in situ hybridization (FISH).
Time Frame: Within a month after taking gastric endoscopy biopsy to confirm the diagnosis of HP infection.
Within a month after taking gastric endoscopy biopsy to confirm the diagnosis of HP infection.
Compare the proportion of Clarithromycin-resistance mutations determined by FISH with the HP eradication rate calculated.
Time Frame: A week after both proportions are calculated.
A week after both proportions are calculated.

Other Outcome Measures

Outcome Measure
Time Frame
Percentage and type of Adverse Events (AEs) and Serious Adverse Events (SAEs) in each group (PLA vs CLA).
Time Frame: Up to a month after the end of both treatments.
Up to a month after the end of both treatments.
Proportion of treatments prematurely suspended due to AEs or SAEs in each group (PLA vs CLA).
Time Frame: Within ten days after each treatment is randomly allocated.
Within ten days after each treatment is randomly allocated.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Asofarma de México S.A de C.V.

Collaborators

Hospital Ángeles, Clínica Londres, Mexico City
Centro InmunoQ, Mexico City
Torre Mayo, Metepec, State of Mexico
Hospital Ángeles Metropolitano, Mexico City
Centro Médico ABC Observatorio, Mexico City

Investigators

  • Principal Investigator: Alma L Ladrón de Guevara, MD

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (Actual)

March 1, 2014

Study Completion (Actual)

May 1, 2014

Study Registration Dates

First Submitted

March 28, 2016

First Submitted That Met QC Criteria

March 28, 2016

First Posted (Estimate)

April 1, 2016

Study Record Updates

Last Update Posted (Estimate)

April 4, 2016

Last Update Submitted That Met QC Criteria

March 31, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ASO HO 01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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