Genotypic Resistance Guided Versus Susceptibility Testing Guided Therapy for the First-line Eradication of H. Pylori

NCT ID: NCT03556254

Last Updated: 2018-10-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 560 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-29
• Study Completion Date: 2022-06-30

Brief Summary

We aimed to (1) compare the efficacy of genotypic resistance guided sequential therapy vs. susceptibility testing guided therapy in the first-line therapy (2) assess the long term impact of eradication therapy on the antibiotic resistance and microbiota of the gut flora and the metabolic factors in this multi-center, open labeled trial

Detailed Description

Background: Recent trials have shown that susceptibility testing guided therapy was more effective than empirical triple therapy given for 7-10 days in the first-line treatment of H. pylori infection. However, susceptibility testing is time consuming and inconvenient, limiting the widespread application of susceptibility testing guided therapy in clinical practice. Recently, point mutations at 23S rRNA and gyrase A have reported to be associated with clarithromycin and levofloxacin resistance. However, whether genotypic resistance guided therapy is more effective or non-inferior to susceptibility guided therapy has not been reported. Besides, the long term impact of H. pylori eradication on the gut microbiota and metabolic disorders remains unclear. Aim: Therefore, we aimed to (1) compare the efficacy of genotypic resistance guided sequential therapy vs. susceptibility testing guided therapy in the first-line therapy(2) assess the long term impact of eradication therapy on the antibiotic resistance and microbiota of the gut flora and the metabolic factorsMethods: This will be a multi-center, open labeled trialPatients: 560 patients with H. pylori infection naïve to eradication therapy will be enrolled Testing for H. pylori infectionBefore First Line TreatmentAny two positive of CLO test, histology, HpSA, and culture will be considered as H. pylori infectedAfter First-Line Treatment: C13-UBT will be used to assess the existence of H. pylori 6-8 weeks after first line therapy. Long term reinfection: C13-UBT will be used to assess the recurrence of H. pylori 1 year after eradication therapy Determination of antibiotic resistance of H. pylori: E-test will be used to determine the minimum inhibitory concentrations of clarithromycin and levofloxacin to guide the selection of antibiotics. Agar dilution test will also be done. Mutations in 23S rRNA and gyrase A will also be determined by PCR followed by direct sequencing Treatment regimens and assignment Eligible patients will be randomized to receive either one of the treatments (A) Genotypic resistance guided therapy: In the absence of 23S rRNA mutation, clarithromycin based sequential therapy will be given. In the presence of 23S rRAN mutation but the absence of gyrase A mutation, levofloxacin based sequential therapy will be given. In the presence of both 23S rRNA and gyrase A mutations or if genotyping fails, bismuth quadruple therapy will be given. (B) Susceptibility testing guided therapy: In the absence of clarithromycin resistance, clarithromycin based sequential therapy will be given. In the presence of clarithromycin resistance but the absence of levofloxacin resistance, levofloxacin based sequential therapy will be given. In the presence of both clarithromycin and levofloxacin resistance or if culture fails, bismuth quadruple therapy will be given. The stool samples will be collected before, and 2 and 8 weeks and 1 year after eradication therapy to analyze the changes in the antibiotic resistance and microbiota of gut floraThe body weight, waist and hip circumference and serum lipid profile, sugar, and HbA1C levels will be collected before and 8 weeks and 1 year after eradication therapy.

Conditions

Helicobacter Pylori Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Genotypic resistance guided therapy

In the absence of 23S rRNA mutation, clarithromycin based sequential therapy will be given. In the presence of 23S rRAN mutation but the absence of gyrase A mutation, levofloxacin based sequential therapy will be given. In the presence of both 23S rRNA and gyrase A mutations or if genotyping fails, bismuth quadruple therapy will be given.

Group Type: EXPERIMENTAL

GGT

Intervention Type: DRUG

In the absence of 23S rRNA mutation, clarithromycin based sequential therapy will be given. In the presence of 23S rRAN mutation but the absence of gyrase A mutation, levofloxacin based sequential therapy will be given. In the presence of both 23S rRNA and gyrase A mutations or if genotyping fails, bismuth quadruple therapy will be given

Susceptibility testing guided therapy

Tailored therapy according to the minimum inhibitory concentration result (susceptibility testing, E-test)

Group Type: ACTIVE_COMPARATOR

SGT

Intervention Type: DRUG

In the absence of clarithromycin resistance, clarithromycin based sequential therapy will be given. In the presence of clarithromycin resistance but the absence of levofloxacin resistance, levofloxacin based sequential therapy will be given. In the presence of both clarithromycin and levofloxacin resistance or if culture fails, bismuth quadruple therapy will be given.

Interventions

GGT

In the absence of 23S rRNA mutation, clarithromycin based sequential therapy will be given. In the presence of 23S rRAN mutation but the absence of gyrase A mutation, levofloxacin based sequential therapy will be given. In the presence of both 23S rRNA and gyrase A mutations or if genotyping fails, bismuth quadruple therapy will be given

Intervention Type: DRUG

SGT

In the absence of clarithromycin resistance, clarithromycin based sequential therapy will be given. In the presence of clarithromycin resistance but the absence of levofloxacin resistance, levofloxacin based sequential therapy will be given. In the presence of both clarithromycin and levofloxacin resistance or if culture fails, bismuth quadruple therapy will be given.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adult patients aged greater than 20 years with H. pylori infection naïve to treatment are considered eligible for enrollment..

Exclusion Criteria

• children and teenagers aged less than 20 years
• history of gastrectomy
• gastric malignancy, including adenocarcinoma and lymphoma
• previous allergic reaction to antibiotics (amoxicillin, clarithromycin, levofloxacin, metronidazole, bismuth) and prompt pump inhibitors (esomeprazole)
• contraindication to treatment drugs
• pregnant or lactating women
• severe concurrent disease

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jyh-Ming Liou

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

National Taiwan University Hospital, Yun-Lin Branch

Yun-Lin County, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Jyh-Ming Liou

Role: CONTACT

jyhmingliou@gmail.com

23123456 ext. 63541

Facility Contacts

Chieh-Chang Chen, MD

Role: primary

References

Chen MJ, Chen PY, Fang YJ, Bair MJ, Chen CC, Chen CC, Yang TH, Lee JY, Yu CC, Kuo CC, Chiu MC, Chou CK, Chen CY, Hu WH, Tsai MH, Hsu YC, Shun CT, Luo JC, Lin JT, El-Omar EM, Wu MS, Liou JM; Taiwan Gastrointestinal Disease and Helicobacter Consortium. Molecular testing-guided therapy versus susceptibility testing-guided therapy in first-line and third-line Helicobacter pylori eradication: two multicentre, open-label, randomised controlled, non-inferiority trials. Lancet Gastroenterol Hepatol. 2023 Jul;8(7):623-634. doi: 10.1016/S2468-1253(23)00097-3. Epub 2023 May 10.

Reference Type: DERIVED

PMID: 37178702 (View on PubMed)

Other Identifiers

201706038MINC

Identifier Type: -

Identifier Source: org_study_id