Helicobacter Pylori and Vonoprazan Dual Therapy

Helicobacter Pylori Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05649709
• Other study ID #: Hp therapy of NCU
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: January 1, 2023
• Est. completion date: December 31, 2023

Study information

• Verified date: December 2022
• Source: The First Affiliated Hospital of Nanchang University
• Contact: Nong-Hua Lu, MD
• Phone: +8613707086809
• Email: lunonghua[@]ncu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

This study was designed as a prospective, open-labeled, randomized non-inferiority 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 low-or high-dose amoxicillin-vonoprazan dual therapy in a 1:1 allocation ratio, a randomization list was generated using Statistical Product Service Solutions (version 25.0). Low-dose amoxicillin-vonoprazan (L-VA) dual therapy consisted of 1000 mg amoxicillin capsules twice daily and 20 mg vonoprazan Fumarate Tablets twice daily for 14 days. High-dose amoxicillin-vonoprazan (H-VA) dual therapy consisted of 1000mg amoxicillin capsules three times daily and 20mg vonoprazan Fumarate Tablets twice daily for 14 days. Patients and investigators were not 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 6-8 weeks after treatment. H. pylori status was considered as negative or positive according to the instructions of the manufacturer. Fecal sample was collected at the timepoint of recheck.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 504
• Est. completion date: December 31, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Helicobacter Pylori

Intervention

Drug:
• L-VA dual therapy
1000mg amoxicillin capsules twice times daily and 20mg vonoprazan Fumarate Tablets twice daily for 14 days
• H-VA dual therapy
1000mg amoxicillin capsules three times daily and 20mg vonoprazan Fumarate Tablets twice daily for 14 days

Locations

Country	Name	City	State
China	The First Affiliated Hospital Of Nanchang University	Nanchang	Jiangxi

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Nanchang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The efficacy of VA dual therapy	The confirmation of H. pylori status was evaluated by urea breath test	6-8 weeks after treatment
Secondary	treatment-emergent adverse events	the frequency and severity of treatment-emergent adverse events	1 day after eradication
Secondary	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
Secondary	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
Secondary	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)