Susceptibility-Guided Sequential Therapy for Helicobacter Pylori Infection

Susceptibility-Guided Sequential Therapy Versus Empirical Therapy for Helicobacter Pylori Infection: a Randomised Controlled Trial

The main objective of this trial is to assess whether a sequential therapy strategy based on molecular antibiotic susceptibility testing (including clarithromycin and fluoroquinolone) for H. pylori infection will improve the eradication rate compared to an empirical therapy.

Study Overview

• Status: Recruiting
• Conditions: Helicobacter Pylori Infection
• Intervention / Treatment: Drug: clarithromycin-sensitive(first-line); Drug: clarithromycin-resistant(first-line); Drug: empirical therapy group first-line; Drug: levofloxacin-sensitive(rescue treatment); Drug: levofloxacin-resistant(rescue treatment); Drug: empirical therapy group rescue treatment

Detailed Description

This trial is designed as a prospective, randomised, open-label, active-controlled and single-centre study. For empirical therapy group(control group), Bismuth quadruple therapy will be an empirical first-line therapy, and high dose dual (proton-pump inhibitor + amoxicillin) treatment will be for rescue therapy if the first-line empirical treat failure. For the susceptibility-guided sequential therapy group, regimens were selected based on H. pylori susceptibility to clarithromycin and levofloxacin. The primary outcome is the first-line eradication rate in both groups, and the overall (including first- and rescue therapies) H. pylori eradication rates in both groups is one of the secondary outcomes. The eradication rates of H. pylori will be analysed by intention-to-treat analysis, modified intention-to-treat analysis and per-protocol analysis.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jing run Zhao, Dr; Phone Number: +86-635-8276373; Email: zhjrun77@163.com

Study Locations

• China
  • Shandong
    • Liaocheng, Shandong, China, 252000
      • Recruiting
      • Liaocheng People's Hospital
      • Contact: Jingrun Zhao, Dr; Phone Number: +86-635-8276373; Email: zhjrun77@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• H. pylori infection was determined using at least one of the following tests: 13C/14C-urea breath test (UBT), stool H. pylori antigen test, rapid urease test, and histological analysis within 4 weeks.
• Patients were naïve to H. pylori treatment.

Exclusion Criteria:

• Allergy to any drug administered.
• Pregnancy and lactation.
• Major systemic diseases, such as severe cardiopulmonary or liver dysfunction.
• Complicated with active peptic ulcer disease, gastric cancer, or prior gastrectomy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: clarithromycin-sensitive(first-line); If H. pylori is sensitive to clarithromycin, we will administer clarithromycin triple therapy-esomeprazole (20 mg, twice daily), clarithromycin (500 mg, twice daily), and amoxicillin (1.0 g, twice daily)-for 14 days	Drug: clarithromycin-sensitive(first-line); esomeprazole (20 mg, twice daily), clarithromycin (500 mg, twice daily), and amoxicillin (1.0 g, twice daily) for 14 days; Other Names: clarithromycin triple therapy
Experimental: clarithromycin-resistant(first-line); If H. pylori is clarithromycin resistance, we selected the High-dose dual therapy (HDDT) regimen as first-line treatment. HDDT-esomeprazole (20 mg, four times daily) and amoxicillin (750 mg, four times daily)-will be used for 14 days.	Drug: clarithromycin-resistant(first-line); esomeprazole (20 mg, four times daily) and amoxicillin (750 mg, four times daily) for 14 days; Other Names: High-dose PPI-amoxicillin dual therapy
Active Comparator: empirical therapy group first-line; The empirical therapy group will receive Bismuth-containing quadruple therapy(BQT) as first-line treatment, The BQT regime is comprising of esomeprazole (20 mg, twice daily), colloidal bismuth pectin (150 mg, four times daily), clarithromycin (500 mg, twice daily), and amoxicillin (1.0 g, twice daily) for 14 days.	Drug: empirical therapy group first-line; esomeprazole (20 mg, twice daily), colloidal bismuth pectin (150 mg, four times daily), clarithromycin (500 mg, twice daily), and amoxicillin (1.0 g, twice daily) for 14 days; Other Names: Bismuth-containing quadruple therapy
Experimental: levofloxacin-sensitive(rescue treatment); If H. pylori was levofloxacin-sensitive, we will use the levofloxacin quadruple regimen as rescue treatment-esomeprazole (20 mg, twice daily), levofloxacin (500 mg, once daily), amoxicillin (1.0 g, twice daily), and colloidal bismuth pectin (150 mg, four times daily)-for 14 days.	Drug: levofloxacin-sensitive(rescue treatment); esomeprazole (20 mg, twice daily), levofloxacin (500 mg, once daily), amoxicillin (1.0 g, twice daily), and colloidal bismuth pectin (150 mg, four times daily) for 14 days; Other Names: levofloxacin quadruple regimen
Experimental: levofloxacin-resistant(rescue treatment); If H. pylori was levofloxacin-resistant, we will use furazolidone quadruple regimen as rescue treatment-esomeprazole (20 mg, twice daily), furazolidone (100 mg, twice daily), amoxicillin (1.0 g, twice daily), and colloidal bismuth pectin (150 mg, four times daily)-for 14 days.	Drug: levofloxacin-resistant(rescue treatment); esomeprazole (20 mg, twice daily), furazolidone (100 mg, twice daily), amoxicillin (1.0 g, twice daily), and colloidal bismuth pectin (150 mg, four times daily) for 14 days; Other Names: furazolidone quadruple regimen
Active Comparator: empirical therapy group rescue treatment; If BQT fails, HDDT-esomeprazole (20 mg, four times daily) and amoxicillin (750 mg, four times daily)-will be used as a rescue treatment for 14 days.	Drug: empirical therapy group rescue treatment; esomeprazole (20 mg, four times daily) and amoxicillin (750 mg, four times daily) for 14 days; Other Names: High-dose PPI-amoxicillin dual therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the first-line H. pylori eradication rate	the proportion of participants with successful H. pylori eradication, as determined by 13C-Urea breath test(UBT), at least 4 weeks after the end of the first-line treatment period between Susceptibility-guided therapy(SGT) and empirical therapy(ET) group.	4-8 weeks after the end of treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the rescue H. pylori eradication rate	The second line eradication rate between SGT and ET group.	4-8 weeks after the second treatment
the overall H.pylori eradication rate	the total H.pylori eradication rate (first-line and second-line)between SGT and ET group.	4-8 weeks after the second treatment
high-dose dual therapy eradication rate	compare H. pylori eradication rate between clarithromycin resistance group and empirical BQT failure group.	4-8 weeks after the second treatment
Adverse events and compliance	3 days after the completion of therapy according to a data collection form	3 days after the end of treatment.

Collaborators and Investigators

• Sponsor: Liaocheng People's Hospital
• Investigators: Study Chair: Jing run Zhao, Dr, Liaocheng People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2022
• Primary Completion (Estimated): February 1, 2024
• Study Completion (Estimated): February 1, 2024

Study Registration Dates

• First Submitted: September 18, 2022
• First Submitted That Met QC Criteria: September 18, 2022
• First Posted (Actual): September 22, 2022

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Helicobacter pylori; Drug Resistance, Microbial; Microbial Sensitivity Tests
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Helicobacter Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; 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; Monoamine Oxidase Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Antacids; Anti-Infective Agents, Urinary; Antitrichomonal Agents; Amoxicillin; Clarithromycin; Levofloxacin; Ofloxacin; Bismuth; Furazolidone
• Other Study ID Numbers: CS-HP001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No