Empirical vs Tailored Therapy for H. Pylori Infection

Comparison of Empirical and Genotypic Resistance Guided Tailored Therapy for Helicobacter Pylori Infection

We aimed to compare the efficacy of genotypic resistance-guided tailored therapy vs empirical therapy for eradication of Helicobacter pylori (H. pylori) infection in randomized controlled trials.

Study Overview

• Status: Unknown
• Conditions: Helicobacter Pylori Infection; Helicobacter Pylori 23S rRNA Clarithromycin Resistance Mutation
• Intervention / Treatment: Combination product: triple therapy; Combination product: quadruple therapy; Diagnostic test: dual-priming oligonucleotide-based multiplex (DPO)-PCR test

Detailed Description

Empirical therapy is conventional triple therapy (proton pump inhibitor (PPI) standard dose, amoxicillin 1 g and clarithromycin 500 mg twice a day for 10 days). Genotypic resistance-guided tailored therapy is the method which is chosen by DPO-PCR test. While the patients who have positive result of clarithromycin resistance receive the quadruple therapy(PPI standard dose, bismuth 300mg twice daily, tetracycline 500 mg four times daily, metronidazole 500mg three times daily for 10 days), clarithromycin susceptible patients receive the triple therapy.

H. pylori is difficult to cultivate, cultivation of H. pylori and minimum inhibitory concentration test as a resistance test method are very difficult and take a long time. Recently, tailored treatment based on clarithromycin susceptibility has been proposed by dual-priming oligonucleotide-based multiplex (DPO)-PCR test. This is a method to confirm the mutation of A2142G and A2143G by PCR, which are known to be highly related to the resistance of clarithromycin 23S rRNA point mutation. This test is performed only by gastric biopsy. The examination time is also short as several hours, and sensitivity and specificity are about 80-85%.

Antibiotic resistance of H. pylori, especially clarithromycin resistance, is a cause of major failure of its eradication, and Korea 's clarithromycin resistance rate is reported to be about 37%. The eradication rate of standard triple therapy reported in Korea is also unsatisfactory as antibiotic resistance rate of H. pylori increases. The ideal eradication rate for H. pylori is approximately 90%, but in the meta-analysis of the recently reported primary eradication, the overall eradication rate was 74.6% in the intention to treat analysis.

• Study Type: Interventional
• Enrollment (Anticipated): 62
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with H. pylori who had undergone endoscopic resection for gastric neoplasm
• Patients with H. pylori who had diagnosed at peptic ulcer disease, MALT lymphoma

Exclusion Criteria:

• history of gastrectomy
• patients aged younger than 20 years or older than 80 years
• history of H. pylori eradication therapies or other antibiotics therapy within a month
• previous allergic reaction to the study drugs (amoxicillin, clarithromycin, metronidazole, tetracycline, and esomeprazole)
• contraindication to treatment drugs
• pregnant or lactating women
• severe concurrent illness

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Empirical group; Patients receive conventional triple therapy containing esomeprazole 40 mg, amoxicillin 1 g and clarithromycin 500 mg twice a day for 10 days	Combination product: triple therapy; esomeprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg twice a day for 10 days
Active Comparator: Genotypic resistance-guided tailored group; Patients receive triple or quadruple therapy by resistance-associated mutations in 23S ribosomal RNA which are identified by polymerase chain reaction (PCR). Triple therapy contains esomeprazole 40 mg, amoxicillin 1 g and clarithromycin 500 mg twice a day for 10 days and quadruple therapy contains esomeprazole 40 mg and bismuth 300mg twice daily, tetracycline 500 mg four times daily, metronidazole 500mg three times daily for 10 days.	Combination product: triple therapy; esomeprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg twice a day for 10 days; Combination product: quadruple therapy; esomeprazole 40 mg and bismuth 300mg twice daily, tetracycline 500 mg four times daily, metronidazole 500mg three times daily for 10 days; Diagnostic test: dual-priming oligonucleotide-based multiplex (DPO)-PCR test; Resistance of clarithromycin 23S rRNA point mutation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eradication rate	Eradication rate of H. pylori infection	13C-UBT at least 4 weeks after completion of treatment

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Soo-Jeong Cho, M.D., ph.D., Department of Internal Medicine and Liver Research Institute,

Publications and helpful links

General Publications

• Kim JL, Cho SJ, Chung SJ, Lee A, Choi J, Chung H, Kim SG. Empiric Versus Clarithromycin Resistance-Guided Therapy for Helicobacter pylori Based on Polymerase Chain Reaction Results in Patients With Gastric Neoplasms or Gastric Mucosa-Associated Lymphoid Tissue Lymphoma: A Randomized Controlled Trial. Clin Transl Gastroenterol. 2020 Sep;11(9):e00194. doi: 10.14309/ctg.0000000000000194.

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2019
• Primary Completion (Anticipated): August 31, 2019
• Study Completion (Anticipated): August 31, 2019

Study Registration Dates

• First Submitted: June 28, 2019
• First Submitted That Met QC Criteria: July 1, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: July 1, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Helicobacter Infections
• Other Study ID Numbers: 1811-029-983

Drug and device information, study documents

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