Helicobacter Pylori and Vonoprazan Dual Therapy

Fourteen-day Vonoprazan and Low-or High-dose Amoxicillin Dual Therapy for Eradicating Helicobacter Pylori Infection: a Prospective, Multi-centers, Open-labeled, Non-inferior, 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. This study evaluated the efficacy and safety of low-and high-dose amoxicillin-vonoprazan dual therapy for 14 days as first-line treatment for H. pylori in China.

Study Overview

• Status: Completed
• Conditions: Helicobacter Pylori
• Intervention / Treatment: Drug: L-VA dual therapy; Drug: H-VA dual therapy

Detailed Description

Upper gastrointestinal endoscopy examinations were performed for all participants and biopsies from gastric antrum and body were obtained. All the collected gastric biopsy specimens were sent to Jiangxi Provincial Key Laboratory of Digestive Diseases, First Affiliated Hospital of Nanchang University for susceptibility testing of antibiotics. The minimum inhibitory concentrations of antibiotics (amoxicillin, metronidazole, clarithromycin, levofloxacin and tetracycline) were determined by E-test. The inhibition zone for furazolidone was determined by the Kirby-Bauer disc diffusion method. Detailed procedure for detecting antibiotics resistance were consistent with our previous study. A strain was considered as resistant if minimum inhibitory concentration >0.125 μg/mL for amoxicillin, >8 μg/mL for metronidazole, ≥1 μg/mL for clarithromycin, >2 μg/mL for levofloxacin, ≥2 μg/mL for tetracycline, the inhibition zone was ≤7mm for furazolidone.

The detailed demographics and characteristics (sex, age, nationality, height, weight, education status, dwelling area, history of smoking and alcohol etc.) were recorded. The treatment-related adverse events (TEAEs) were recorded. We defined adherence as good if the participants took ≥80% drugs of the regimen during the consecutive 14 days. The H. pylori status after therapy was evaluated by ¹³C-UBT at least 6 weeks after completion of treatment. Proton pump inhibitors and antibiotics were stopped at least 2 and 4 weeks before ¹³C-UBT, respectively.

The stool samples were collected at baseline (before treatment), week 2 (after eradication) and week 8-10 (confirmation of H. pylori status). We sent the stool samples from subjects with successful eradication for metagenome DNA extraction and shotgun sequencing to avoid the influence of H. pylori eradication failure on gut microbiota. Briefly, OMEGA Mag-Bind Soil DNA Kit (Omega Bio-Tek, Norcross, GA, USA) was used to extract total microbial genomic DNA samples. Metagenome shotgun sequencing libraries from extracted microbial DNA was constructed by Illumina TruSeq Nano DNA LT Library Preparation Kit, which was then sequenced by Illumina NovaSeq platform (Illumina, USA) with PE150 strategy at Personal Biotechnology Co., Ltd. (Shanghai, China).

Raw sequencing reads were subjected to processing to yield quality-filtered reads suitable for further analysis, including removal of adapter and low-quality reads. Subsequently, minimap2 was utilized to align reads to the host genome of human and eliminate host contamination. Gene prediction was carried out on the generated contigs from each sample, whose translated protein sequences were subsequently pooled and clustered using mmseqs2. The lowest common ancestor taxonomy of the non-redundant genes was ascertained using mmseqs2 in "taxonomy" mode, by aligning them against a customized database comprising protein sequences of bacteria from GTDB (release 207: https://data.ace.uq.edu.au/public/gtdb/data/releases/), fungi from NCBI-nr (https://ftp.ncbi.nlm.nih.gov/blast/db/FASTA/), and viruses from RVDB (version 24.1: https://rvdb.dbi.udel.edu/download/). In order to assess the abundance of genes, high-quality reads from each sample were mapped onto the contigs using minimap2 and read counts were computed using htseq. Abundance values in metagenomes were normalized using copies per kilobase per million mapped reads. Clean high-quality reads were processed and profiled with ARGs-OAP (version 2.0) by querying against the SARG (version 3.0-F) database, which is a structural antimicrobial resistance genes database containing 32 types and 2842 subtypes of antibiotic resistance genes. In order to perform the quantification and downstream analysis of diversity indices, resistome profiling, and prevalence ranking, the abundance of antibiotic resistance genes at type and subtype level were normalised to the number of 16S rRNA genes.

• Study Type: Interventional
• Enrollment (Actual): 504
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

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

Exclusion Criteria:

• allergy to amoxicillin or vonoprazan;
• acute upper gastrointestinal bleeding, gastric cancer or other tumors, Zollinger-Ellison syndrome, history of gastric surgery;
• serious illness including neurological, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, endocrinological or hematological disorders;
• pregnancy or breast feeding;
• proton pump inhibitors and antibiotics 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: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vonoprazan and low-dose amoxicillin dual therapy; 1000 mg amoxicillin capsules twice daily and 20 mg vonoprazan Fumarate Tablets twice daily for 14 days	Drug: L-VA dual therapy; 1000mg amoxicillin capsules twice times daily and 20mg vonoprazan Fumarate Tablets twice daily for 14 days; Other Names: L-VA
Active Comparator: vonoprazan and high-dose amoxicillin dual therapy; 1000mg amoxicillin capsules three times daily and 20mg vonoprazan Fumarate Tablets twice daily for 14 days	Drug: H-VA dual therapy; 1000mg amoxicillin capsules three times daily and 20mg vonoprazan Fumarate Tablets twice daily for 14 days; Other Names: H-VA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The efficacy of VA dual therapy	The confirmation of H. pylori status was evaluated by urea breath test	6-8 weeks after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
treatment-emergent adverse events	the frequency and severity of treatment-emergent adverse events	1 day after eradication
compliance	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
the alteration of gut microbiota	The 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（6-8 weeks after treatment）

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Nanchang University
• Investigators: Principal Investigator: Nong-Hua Lu, phD, The First Affiliated Hospital of Nanchang University

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2023
• Primary Completion (Actual): January 25, 2024
• Study Completion (Actual): January 25, 2024

Study Registration Dates

• First Submitted: November 27, 2022
• First Submitted That Met QC Criteria: December 5, 2022
• First Posted (Actual): December 14, 2022

Study Record Updates

• Last Update Posted (Actual): August 23, 2024
• Last Update Submitted That Met QC Criteria: August 21, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Helicobacter pylori; amoxicillin; vonoprazan; eradication
• Other Study ID Numbers: Hp therapy of NCU

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