Prospective Randomised Trial of First and Second Line Treatments of RCT of First and Second Line H Pylori Treatments in Slovenia

Prospective Randomised Trial of First and Second Line Treatments of Helicobacter Pylori Infection in Slovenia

Study is prospective randomised multicentric. The primary objective of the study is to compare the efficacy of two first-line therapy regimens and two second-line therapy regimens (ie, after failure of first-line treatment) in patients with H. pylori infection. The secondary objective of the study is to determine the primary resistance of H. pylori to antibiotics in Slovenia.

Study Overview

• Status: Not yet recruiting
• Conditions: Helicobacter Pylori Infection; Eradication Treatments
• Intervention / Treatment: Drug: Esomeprazole 40mg, Clarithromycin 500 mg, Metronidazole 400 mg,; Drug: Esomeprazole 40mg, Bismuth subcitrate 120 mg, Amoxicillin 500 mg, Metronidazole 400 mg; Drug: Esomeprazole 40mg, Bismuth subcitrate 120 mg, Amoxicillin 500 mg, Metronidazole 400 mg; Drug: Esomeprazole 40mg, Amoxicillin 500 mg, Levofloxacin 500 mg

Detailed Description

The infection with Helicobacter pylori is extremely widespread, as 60% of the world's population is infected. In Slovenia, the average prevalence is 25.1 %, the prevalence in the 20-year age group is 20 % and 76 % in patients in age group 50 - 75 years. All infected patients have active chronic gastritis, which is asymptomatic in most cases. Ulcers in the stomach or duodenum occurs in 15 % of patients. Due to chronic infection, MALT lymphoma or gastric cancer develop in 1 - 3 % of patients. According to the recommendations of the Slovenian Association for Gastroenterology and Hepatology, as well as European and other recommendations, everyone who is infected with Helicobacter pylori should be treated. H. pylori is a first-class carcinogen and is responsible for 50 % of all chronic cancer-causing infections in the developed world. Therefore, it is necessary to start programs of primary and secondary prevention of gastric cancer by searching and treating infected patients.

Patients infected with H. pylori who have not yet been treated will be randomly assigned to two first-line treatment groups:

Group 1: Esomeprazole 40 mg, Clarithromycin 500 mg, Amoxicillin 1000 mg, all BID,14 days Group 2: Bismuth subcitrate 120 mg, Amoxicillin 500 mg, Metronidazole 400 mg, all QID Esomeprazole 40 mg BID, 14 days

Patients unsuccessfully treated with first-line therapy will be randomly assigned to two second-line treatment groups:

Group 1: Esomeprazole 40 mg BID, Levofloxacin 500 mg OID, Amoxicillin 1000 mg BID, 14 days Group 2: Bismuth subcitrate 120 mg, Amoxicillin 500 mg, Metronidazole 400 mg, all QID, Esomeprazole 40 mg BID, 14 days

Inclusion criteria :

Patients 18 to 80 years of age. Patients have not received proton pump inhibitors for the past 14 days. Patients did not receive antibiotics last month. Helicobacter pylori infection has been demonstrated by rapid urease test

Exclusion criteria :

Prior treatment for Helicobacter pylori infection (in patients who will receive Schedule 1 eradication therapy).

Defects in blood clotting. taking anticoagulant medicines that make it impossible to take biopsies.

Drug allergy used in the study. Pregnancy, breastfeeding. Psychiatric illness that would prevent research participation. Active treatment for malignancy.

Statistical analysis:

To describe the variables, we will use the average value and standard deviation for the symmetrically distributed variables or median and 25th and 75th percentiles for asymmetrically distributed variables. Investigators will use the t-test for dependent variables or, in the case of asymmetrically distributed variables, the Wilcoxon test. To determine the differences between the two groups (Group 1 and Group 2) of the subjects, t-test for independent samples Will be used, or in the case of an asymmetrically distributed variables Mann-Whitney test.

• Study Type: Interventional
• Enrollment (Anticipated): 560
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: BOJAN TEPES; Phone Number: 0038641325916 0038641325916; Email: bojan.tepes@siol.net

Study Locations

• Slovenia
  • Bled, Slovenia, 4260
    • DC BLED
    • Contact: Milan Stefanovič; Email: milan.stefanovic@dc-bled.si
    • Sub-Investigator: Milan Stefanovič, MD
  • Ljubljana, Slovenia, 1000
    • UCC
    • Contact: Borut Stabuc, MD PhD; Email: borut.stabuc@kclj.si
    • Principal Investigator: Borut Stabuc, MD PhD
  • Rogaška Slatina, Slovenia, 3250
    • Am Dc Rogaska
    • Contact: Prof B TEPES; Phone Number: 0038641325916 0038641325916; Email: bojan.tepes@siol.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Patients 18 to 80 years of age.
• Patients have not received proton pump inhibitors for the past 14 days.
• Patients did not receive antibiotics in the last month.
• Helicobacter pylori infection has been demonstrated by rapid urease test.

Exclusion Criteria:

• Prior treatment for Helicobacter pylori infection (in patients who will receive Schedule 1 eradication therapy).•
• Defects in blood clotting. taking anticoagulant medicines that make it impossible to take biopsies.
• Allergy to drugs used in the study.
• Pregnancy, breastfeeding shold be excluded.
• Psychiatric illness that would prevent research participation.
• Active treatment for malignancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: First line therapy for H pylori infection; Tripple 14 day first line therapy Esomeprazole 40 mg, Clarithromycin 500 mg, Amoxicillin 1000 mg, all BID 14 days	Drug: Esomeprazole 40mg, Clarithromycin 500 mg, Metronidazole 400 mg,; First line therapy; Other Names: Emozul, Fromilid,Efloran
EXPERIMENTAL: First line therapy for H pylori infection second arm; Bismuth quadruple first line therapy Bismuth subcitrat 120 mg , Amoxicillin 500 mg, Metronidazole 400 mg, all QID, Esomeprazole 40 mg BID, 14 days.	Drug: Esomeprazole 40mg, Bismuth subcitrate 120 mg, Amoxicillin 500 mg, Metronidazole 400 mg; First line therapy second arm; Other Names: Emozul, Bismut oksid Krka, Hiconcil, Efloran; Drug: Esomeprazole 40mg, Bismuth subcitrate 120 mg, Amoxicillin 500 mg, Metronidazole 400 mg; Second line therapy for Helicobacter pylori infection; Other Names: Emozul, Bismut oksid Krka, Hiconcil, Efloran
ACTIVE_COMPARATOR: Second line therapy for H pylori infection; Bismuth quadruple second line therapy for those treated with Tripple first line therapy Bismuth subcitrat 120 mg , Amoxicillin 500 mg, Metronidazole 400 mg, all QID, Esomeprazole 40 mg BID, 14 days.	Drug: Esomeprazole 40mg, Bismuth subcitrate 120 mg, Amoxicillin 500 mg, Metronidazole 400 mg; First line therapy second arm; Other Names: Emozul, Bismut oksid Krka, Hiconcil, Efloran; Drug: Esomeprazole 40mg, Bismuth subcitrate 120 mg, Amoxicillin 500 mg, Metronidazole 400 mg; Second line therapy for Helicobacter pylori infection; Other Names: Emozul, Bismut oksid Krka, Hiconcil, Efloran
EXPERIMENTAL: Second line therapy for H pylori infection second arm; Tripple second line therapy Esomeprazol 40 mg BID Amoxicillin 1000 mg BID, Levofloxacin 500 mg OID, 14 days or	Drug: Esomeprazole 40mg, Amoxicillin 500 mg, Levofloxacin 500 mg; Second line therapy for Helicobacter pylori infection second arm; Other Names: Emozul, Hiconcil,Tavanic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success rate of first line therapy for Helicobacter pylori infection	Eradication rate	2 years
Success rate of second line therapy for Helicobacter pylori infection	Eradication rate	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Helicobacter pylori resistance rate to antibiotics	Culture and susceptibility testing	3 years

Collaborators and Investigators

• Sponsor: Slovenian Society for Gastroenterology and Hepatology
• Collaborators: KRKA
• Investigators: Principal Investigator: BOJAN TEPES, Am Dc Rogaska

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 10, 2020
• Primary Completion (ANTICIPATED): May 31, 2023
• Study Completion (ANTICIPATED): September 30, 2023

Study Registration Dates

• First Submitted: April 17, 2020
• First Submitted That Met QC Criteria: April 23, 2020
• First Posted (ACTUAL): April 24, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 23, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Helicobacter pylori; First line treatment; Second line treatment; susceptibility to antibiotics
• Additional Relevant MeSH Terms: Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Helicobacter Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Gastrointestinal Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Antacids; Anti-Infective Agents, Urinary; Renal Agents; Metronidazole; Amoxicillin; Clarithromycin; Levofloxacin; Ofloxacin; Esomeprazole; Bismuth; Bismuth tripotassium dicitrate
• Other Study ID Numbers: SZGH Krka

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No