Clinical trial NCT03124199: Rifaximin Associated With Classic Triple Therapy for the Eradication of Helicobacter Pylori Infection
Official title: Rifaximin Associated With Classic Triple Therapy (Inhibitor of Proton Pump, Amoxicillin and Clarithromycin) for the Eradication of Helicobacter Pylori Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bacterial Infection Due to Helicobacter Pylori (H. Pylori)
Keywords: Eradication
Helicobacter pylori
rifaximin
therapy
standard triple therapy
Lead sponsor: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Sponsor class: OTHER
First posted: 2017-04-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With H.Pylori Infection Eradication
timeFrame: 1 month
Secondary outcomes:
measure: Tolerability of Treatment
timeFrame: 1 month
measure: Compliance With Treatment of Patients That Completed the Study
timeFrame: 1 month
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
Study officials:
affiliation: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
name: Javier Perez, Gisbert
role: PRINCIPAL_INVESTIGATOR
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