Helicobacter Pylori and Lacidophilin Tablets in Combination With Vonorazan Dual Therapy

Lacidophilin Tablets in Combination With Vonorazan and Amoxicillin Dual Therapy for Eradicating Helicobacter Pylori Infection: a Prospective, Multi-centers, Superiority, Double-blind, Randomized Clinical Study

Our previous study included 119 Helicobacter pylori(H. pylori)-infected Chinese patients without previous eradication history who were randomized to low-or high-dose amoxicillin-vonoprazan regimens consisting of amoxicillin 1 gram either b.i.d. or t.i.d plus vonoprazan 20 mg b.i.d for 7 or 10 days. Neither 7-or 10-day VA dual therapy with either b.i.d. or t.i.d. amoxicillin achieved satisfied efficacy (i.e., <90%) when given as first-line treatment for H. pylori infection. Lacidophilin tablets have been reported to increase the eradication rate of H. pylori while reducing the incidence of adverse effects.This study evaluated the efficacy and safety of lacidophilin tablets in combination with amoxicillin-vonoprazan dual therapy for 10 days as first-line treatment for H. pylori in China.

Study Overview

• Status: Active, not recruiting
• Conditions: Helicobacter Pylori Infection
• Intervention / Treatment: Drug: Lacidophilin tablets in combination with vonorazan dual therapy; Drug: Placebo in combination with vonorazan dual therapy

Detailed Description

This study was designed as a prospective, multi-centers, double-blind, randomized superiority clinical study and was conducted in accordance with the Declaration of Helsinki and the guidelines of the Consolidated Standards of Reporting Trials.

Consecutive H. pylori-infected subjects ages from 18 to 70 without eradication history were recruited . H. pylori infection was confirmed by immunohistochemistry or urea breath test.

The H. pylori-infected subjects were randomly assigned to receive lacidophilin tablets or placebo in combination with amoxicillin-vonoprazan dual therapy for in a 1:1 allocation ratio, a randomization list was generated using Statistical Product Service Solutions (version 25.0).

The therapy consisted of 2400mg lacidophilin tablets or placebo three times daily, 1000 mg amoxicillin capsules three times daily and 20mg vonoprazan fumarate tablets twice daily for 10 days. The shape, taste, packaging, storage method and administration method of placebo are the same as lacidophilin tablets. Participants and investigators were blinded to the allocated treatment group.

At the start, the detailed demographics and characteristics of the subjects included in this study were recorded, including sex, age, nationality, height, weight, education status, dwelling area, history of smoking and alcohol, concomitant diseases and medication history. In addition, physical examinations and assessment of vital signs were performed. Gastric antrum and body biopsy of the included subjects were obtained during the endoscopy, which were followed by culture and susceptible test of antibiotics. Fecal sample was collected before eradication.

During (or after) treatment-emergent adverse events (TEAEs) and concomitant medication were recorded throughout the study, including bloating, nausea, vomiting, abdominal pain, diarrhea, constipation, skin rash, headache, hunger sensation and others. All TEAEs were divided into mild, moderate and severe, TEAEs leading to study drug discontinuation were also recorded. Fecal sample was collected after eradication.

The confirmation of H. pylori status was evaluated by 13C-urea breath test 4-8 weeks after treatment. H. pylori status was considered as negative or positive according to the instructions of the manufacturer. Oral and fecal sample was collected at the timepoint of recheck.

• Study Type: Interventional
• Enrollment (Estimated): 324
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Nong-Hua Lu, MD; Phone Number: +8613707086809; Email: lunonghua@ncu.edu.cn
• Study Contact Backup: Name: Yin Zhu, phD; Phone Number: +8613970841464; Email: zhuyin27@sina.com

Study Locations

• China
  • Jiangxi
    • Nanchang, Jiangxi, China
      • The first affiliated hospital, Jiangxi Medical College, NanChang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Consecutive H. pylori-infected subjects ages from 18 to 70 without eradication history

Exclusion Criteria:

• allergy to amoxicillin,vonoprazan or lacidophilin tablets;
• acute upper gastrointestinal bleeding, gastric cancer or other tumors, Zollinger-Ellison syndrome, history of gastric surgery;
• gastroscopy report showing or past medical history of significant esophagogastric disease, including gastric cancer, peptic ulcer, esophagitis, esophageal erosion.
• serious illness including neurological, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, endocrinological or hematological disorders;
• pregnancy or breast feeding;
• proton pump inhibitors, antibiotics and probiotics use within one month;
• not willing to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lacidophilin tablets group; 2400mg lacidophilin tablets three times daily,1000mg amoxicillin capsules three times daily and 20mg vonoprazan Fumarate Tablets twice daily for 10 days	Drug: Lacidophilin tablets in combination with vonorazan dual therapy; 2400mg lacidophilin tablets three times daily,1000mg amoxicillin capsules three times daily and 20mg vonoprazan Fumarate Tablets twice daily for 10 days
Placebo Comparator: Placebo group; 2400mg placebo three times daily,1000mg amoxicillin capsules three times daily and 20mg vonoprazan Fumarate Tablets twice daily for 10 days	Drug: Placebo in combination with vonorazan dual therapy; 2400mg placebo three times daily,1000mg amoxicillin capsules three times daily and 20mg vonoprazan Fumarate Tablets twice daily for 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of Treatment	The confirmation of H. pylori status was evaluated by urea breath test	4-8 weeks after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	the frequency and severity of treatment-emergent adverse events	1 day after eradication
Compliance of Participants	good compliance was defined as achieving ≥80% of drugs included in the regimes and bad compliance was defined as achieving <80% drugs	1 day after eradication
Resistance of Antibiotics	An E-test was used to determine the minimum inhibitory concentrations (MIC) of Amoxicillin (AMO), Metronidazole (MET), Clarithromycin (CLA), Levofloxacin (LEV) and tetracycline (TET). The Kirby-Bauer disc diffusion method (Oxoid) was used to determine the inhibition zone for Furazolidone (FUR). A strain was considered resistant if the MIC>1 mg/mL for AMO, ≥1 mg/mL for CLA, >2 mg/mL for TET, >4 mg/mL for MET, MIC >1 mg/mL for LEV and if the inhibition zone was <7 mm for FUR. H. pylori strain ATCC 43504 was included as an antibiotic susceptibility testing qualitycontrol. All antibiotic susceptibility tests were conducted at the Institute of Gastroenterology and Hepatology, First Affiliated Hospital of Nanchang University.	before the eradication
Alteration of Gut Microbiota	The oral and fecal samples were collected before eradication,1 day after eradication and confirmation（6-8 weeks after treatment）. Bioinformatics of gut microbiome were performed using QIIME2 with slight modification and R packages. Briefly, Non-singleton ASVs were aligned and used to construct a phylogeny with fasttree2. Alpha-diversity metrics were calculated using the ASV table in QIIME2 and visualized as box plots. ASV-level ranked abundance curves were generated to compare the richness and evenness of ASVs among samples. Beta diversity analysis was conducted to explore the structural variation of microbial communities across samples using Bray-Curtis metrics and visualized via principal coordinate analysis (PCoA). The significance of microbiota structure differences among groups was assessed by Permanova using QIIME2. Microbial functions were predicted by PICRUSt2 upon KEGG (https://www.kegg.jp/) databases.	before eradication，1 day after eradication and confirmation（4-8 weeks after treatment）

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Nanchang University
• Investigators: Principal Investigator: Cong He, phD, The First Affiliated Hospital Of Nanchang University

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2023
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: February 18, 2023
• First Submitted That Met QC Criteria: February 18, 2023
• First Posted (Actual): March 1, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Helicobacter pylori; amoxicillin; vonoprazan; eradication; Lacidophilin Tablets
• Additional Relevant MeSH Terms: Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Helicobacter Infections
• Other Study ID Numbers: Hp therapy of FirstNanchangU

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