Efficacy and Safety of Quadruple Therapy in Eradication of H. Pylori: A Comparison to Triple Therapy

Study Overview
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Brief Summary
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This study aims at evaluating efficacy and safety of quadruple therapy (bismuth, metronidazole, tetracycline and omeprazole: OBMT) vs triple therapy (amoxicillin, clarithromycin and omeprazole: OAC) in H. Pylori eradication. It is hypothesized that quadruple therapy will be comparable in efficacy to triple therapy. Subjects with confirmed H. pylori positive status will be randomized to one of the treatments described above. At week 6 and 10 follow-up visits, a urea breath test (UBT) will be performed to confirm eradication.

Detailed Description
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The study will include three phases: screening, treatment and follow-up. Screening: this phase will last a maximum of 30 days and subjects eligibility will be evaluated after informed consent signature. Endoscopy and Urea Breath test will be performed in addition to the baseline routine evaluations. Treatment: Subjects assigned to OAC will be treated for 7 days. Those assigned to Pylera will be treated for 10 days. A randomization visit will take place on Day 0 and an end-of-treatment visit will take place between day 8 and 14. Follow-up: includes two visits. approximately one and two months post-treatment. Eradication of H. Pylori will be confirmed through UBT, and resistance will be evaluated in case of treatment failure. These subjects will undergo an endoscopy.

Official Title
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Efficacy and Safety of Quadruple Therapy by Bismuth Subcitrate Potassium, Metronidazole, and Tetracycline Given X 10 Days With Omeprazole in Eradication of Helicobacter Pylori: A Comparison to Omeprazole, Amoxicillin and Clarithromycin Given X 7 Days

Conditions
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Helicobacter Infections

Intervention / Treatment
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* Drug: Omeprazole, amoxicillin, clarithromycin
* Drug: Pylera (Bismuth subcitrate potassium, metronidazole, tetracycline) given in combination with omeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive H. Pylori status; Presence of upper gastro-intestinal symptoms; Mental and legal ability to sign informed consent. Exclusion Criteria: Previous surgery of the GI tract; Clinically significant impairment of renal or hepatic function; Severe unstable cardiovascular, pulmonary or endocrine disease; Barrett's oesophagus or high-grade dysplasia; Dysphagia or vomiting as major symptoms.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: OAC 7 days<br>Triple therapy, given for 7 days at a dose of omeprazole 20 mg twice daily, amoxicillin 500 mg 2 capsules twice daily, and clarithromycin 500 mg 1 tablet twice daily | Drug: Omeprazole, amoxicillin, clarithromycin<br>* Triple therapy given for 7 days at a dose of omeprazole 20 mg BID, amoxicillin 500 mg 2 capsules BID, and clarithromycin 500 mg 1 tablet BID<br>|
| Experimental: OBMT 10 days<br>OBMT (Pylera), consisting of a 3 in 1 capsule, made of bismuth subcitrate potassium 120 mg, metronidazole 125 mg, and tetracycline 125 mg, administered as 3 capsules 4 times daily. Omeprazole 20 mg is administered twice daily. | Drug: Pylera (Bismuth subcitrate potassium, metronidazole, tetracycline) given in combination with omeprazole<br>* Pylera is a three in one capsule containing bismuth subcitrate potassium 120 mg, metronidazole 125 mg and tetracycline 125 mg given as 3 capsules QID, with omeprazole 20 mg BID.<br>* Other names: Pylera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Helicobacter Pylori Eradication Confirmed by Urea Breath Test | H. pylori Eradication defined as a negative C13-UBT (urea breath test) result at both Week 6 and Week 10 follow-up visits. | Week 6 and week 10 follow-up visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Experiencing Treatment Emergent Adverse Events. | A treatment-emergent adverse event is defined as an event not present prior to exposure to the study medication or any event already present that worsens in either intensity or frequency following exposure to study medication up to 30 days after study discontinuation. All safety analysis based on the safety population. | at the end of treatment (day 8-14), week 6 and wek 10 follow-up visits. | 
| H. Pylori Eradication and Presence or Past History of Peptic Ulcers | Eradication rates in the subset of patients with peptic ulcer (current or past history) at baseline are reported based on the per protocol population. Eradication must be confirmed at week 6 and week 10 by a negative Urea Breath Test conducted within the allocated windows. | Week 6 and week 10 follow-up visits | 
| Clarithromycin Resistance | Eradication rates in subset of patients infected with a bacterial strain confirmed as resistant to clarithromycin at baseline. Resistance to clarithromycin defined as Minimum Inhibitory Concentration (MIC) of 1 ug/ml and above | Measured at baseline | 
| Metronidazole Resistance | Eradication rates in subset of patients infected with a bacterial strain confirmed as resistant to metronidazole at baseline. Resistance to metronidazole defined as Minimum Inhibitory Concentration (MIC) above 8 ug/ml | Measured at baseline | 
| Overall Compliance to Study Medications | Overall compliance: number of capsules dispensed - number of capsules returned/Number of prescribed capsules X 100. Percentages based on safety population | At the end of the treatment phase (days 8-14) | 
| Number of Patients With Bismuth Plasma Concentrations Above the Toxic Level | Tolerability of OBMT with respect to plasma bismuth concentrations: number of patients with bismuth concentrations above the toxic level (50 ug per liter) | Baseline (both arms), end of treatment (Day 11-14) and end of study (Day 70) OBMT arm only | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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H. Pylori, Quadruple therapy, Eradication rate, Multinational trial, Resistance to antibiotics, Subjects with confirmed Helicobacter Pylori infection