Rifaximin Associated With Classic Triple Therapy for the Eradication of Helicobacter Pylori Infection
Rifaximin Associated With Classic Triple Therapy for the Eradication of Helicobacter Pylori Infection
Background: A progressive decrease in Helicobacter pylori eradication rates has been
 described over the years, so new combinations of antibiotics for treatment are needed.

 Aim: To evaluate the efficacy and safety of the addition of rifaximin to standard triple
 therapy (omeprazole, amoxicillin and clarithromycin) for the eradication of H. pylori.

 Methods: Independent prospective pilot clinical trial (EUDRA CT: 2013-001080-23). Forty
 consecutive adult patients were included with H. pylori infection, dyspeptic symptoms and
 naive to eradication treatment. A full blood test was performed in the first 5 patients
 included to evaluate the safety of the treatment. H. pylori eradication was confirmed with
 urea breath test at least 4 weeks after the end of treatment. Treatment: Rifaximin 400 mg/8
 h, clarithromycin 500 mg/12 h, amoxicillin 1 g/12 h, and omeprazole 20 mg/12 h for 10 days.
4. STUDY DESIGN 4.1. Endpoints Main endpoint Eradication of infection "by intention to
 treat". Secondary endpoints Eradication of infection "per protocol". Adherence to treatment.
 Medication side effects.

 Clinical and demographic variables:

 1) Age; 2) Sex; 3) Smoking habit; 4) Comorbidity (diabetes mellitus, hypertension, ischemic
 heart disease, dyslipidemia, others); 5) Indication of eradication (peptic ulcer vs.
 functional dyspepsia or not investigated) 6) Initial diagnosis test of H. pylori infection.

 4.2. Clinical trial design Phase III clinical trial, prospective, pilot, open, not
 controlled. The recruitment period will be five months. All the tests to confirm infection
 with Helicobacter pylori made within a maximum period of one year, provided the patient has
 not taken any antibiotics able to eradicate bacteria from conducting the test until the day
 of inclusion, will be given as valid, for the inclusion of the patient, Patients with proven
 infection and that have already prescribed standard triple therapy by routine clinical
 practice, will be required written informed consent to participate in the study, after which
 treatment with Rifaximin will be added.

 1. At the time of enrollment, after reviewing the inclusion and exclusion criteria and
 obtaining the patient's consent, a medical history and complete examination will take
 place including: antiulcer treatment received, history of smoking and alcohol intake,
 aspirin consumption and NSAID. Other concomitant medications that the patient is
 receiving for any other process will be also recorded.

 2. Between days 5-15 after taking the last dose, the procedures of the follow up visit
 specified in section 7.3.2 will be performed to the patients. Similarly, these
 procedures will be performed at the time when the patient leaves the study prematurely,
 if need be.

 3. Control breath test or histology between 4 and 8 weeks after treatment ends. Before the
 control test, it will be confirmed that the patient has not taken proton pump inhibitors
 during the 15 days before or antibiotics within 4 weeks prior to the breath test.

 The breath test is approved for the detection of H. pylori infection and post-eradication
 control. Sample collection can be performed in the same hospital.

 Breath test has been chosen as post-eradication control because it is the test that, in
 isolation, has a higher diagnostic accuracy, so is currently considered as the diagnostic
 method of choice to confirm eradication of H. pylori. In cases of gastric ulcer where
 gastroscopy after treatment control is required, the biopsy is valid also as post-eradication
 control.

 A single test post-treatment control is requested at least four weeks after completion of
 therapy since it has been observed an excellent correlation between it and the long-term
 results in previous studies.

 4.3. Treatment Description Control treatment: N/A Experimental treatment: rifaximin 400 mg (2
 tablets of Rifaximin 200 mg)/8 hours for 10 days.

 Study medication will be donated by "Alfa Wassermann" and re-labeled in accordance with the
 recommendations of the Royal Decree 223/2004 for medication trials.

 4.5. Withdrawal criteria and analysis The patient can discontinue his/her participation in
 the study at any time he/she wishes. In his opinion and judgment, the researcher doctor may
 also decide to withdraw a patient from the trial if it does not comply with the protocol.

 The occurrence of chronic diseases during the trail will result in the permanent exclusion of
 the subject. The onset of acute pathology during the trial period will delay the
 administration of test drugs until the patient is healed. Patients who may vomit within 3
 hours after taking the drug (verified by asking the patient) or other clinically relevant
 process that may affect the pharmacokinetics of study drug, will be excluded from analysis
 Only subjects excluded from the trial before receiving the study medication will be replaced
 by others, so that the number of patients will remain as provided by the sample size
 calculation. Individual sheets of collecting data from these excluded subjects will also be
 sent to the Sponsor organization for evaluation.

 4.6. Investigational drug accountability procedures Patients will receive Rifaximin and will
 be asked to return the remaining investigational medication in follow up visit after
 treatment. They will be asked to collaborate also bringing the remains of standard triple
 therapy for counting. The doctor will ask the patient about treatment compliance and count
 the residual medication after which he will return the remains of the standard triple therapy
 to the patient and preserve the remains of Rifaximin for later destruction by appropriate
 methods.

 4.8. Definition of end of trial Date on which the last patient completed the study follow-up
 visit.
Inclusion Criteria:

 1. Age greater than or equal to 18 years.

 2. Patients with dyspeptic symptoms, ie pain or discomfort (including abdominal bloating,
 early satiety and bloating) centered on the upper abdomen, persistent or recurrent,
 with proven H. pylori infection (through testing breath or gastric biopsy based
 methods, if it has been done) with a validity period of one year.

 3. Having been previously prescribed by routine clinical practice the standard triple
 therapy as eradication treatment:

 -  Proton Pump Inhibitor. Omeprazole 40 mg (or equivalent) every 12 hours. Treatment
 duration: 10 days.

 -  Clarithromycin. Dose: 500 mg every 12 hours. Treatment duration: 10 days.

 -  Amoxicillin. Dose: 1000 mg every 12 hours. Treatment duration: 10 days.

 4. Not having yet begun taking the eradication therapy.

 5. Written informed consent from the patient.

 6. The first five patients included in the study, should had cited from the outpatient
 and prior to his arrival in consultation, a routine analysis in the month after the
 completion of the eradication therapy.

 7. If the patient is a woman of childbearing age, she will be asked to commit to not get
 pregnant or to use an adequate contraception method.

 Exclusion Criteria:

 1. Previous eradication treatment for H. pylori (these patients are often carriers of
 antibiotic resistant strains and have a much lower response than those that had never
 received treatment).

 2. Allergy to any of the antibiotic in the treatment.

 3. Taking antibiotics or bismuth salts since performing the breath test.

 4. Previous gastric surgery.

 5. Presence of severe pulmonary, hepatic, renal, endocrine, metabolic, hematologic or
 tumor disease.

 6. Very advanced chronic disease or other conditions that prevent attending to controls
 and follow ups.

 7. Previous history of alcohol or drugs abuse.

 8. Patients who are pregnant or lactating.