Helicobacter Rescue Therapy With High-dose Esomeprazole and Amoxicillin Dual Therapy Versus Bismuth-containing Quadruple Therapy

Rescue Therapy for Helicobacter Pylori Eradication: A Randomized and Non-inferiority Trail of High-dose Esomeprazole and Amoxicillin Dual Therapy Versus Bismuth-containing Quadruple Therapy

This study aims at evaluating efficacy and safety of high-dose esomeprazole and amoxicillin dual therapy(esomeprazole and amoxicillin) versus bismuth-containing quadruple Therapy(bismuth，esomeprazole，tetracycline and furazolidone) in H. pylori rescue therapy. It is hypothesized that high-dose esomeprazole and amoxicillin dual therapy is non-inferior to bismuth-containing quadruple Therapy. Patients with confirmed failure of H. pylori eradication will be randomized to one of the treatments described above. At week 6 follow-up visits, a urea breath test，rapid urease test or helicobacter pylori stool antigen test will be performed to confirm eradication.

Study Overview

• Status: Enrolling by invitation
• Conditions: Gastritis; Dyspepsia; Gastric Cancer; Peptic Ulcer; Helicobacter Pylori Infection
• Intervention / Treatment: Drug: Esomeprazole; Drug: Amoxicillin; Drug: Esomeprazole; Drug: Bismuth; Drug: Tetracycline; Drug: Furazolidone

Detailed Description

The study will include three phases: screening, treatment and follow-up.

Screening: this phase will last a maximum of 14 days and subjects eligibility will be evaluated after signing informed consent. One of urea breath test，rapid urease test or helicobacter pylori stool antigen test will be performed in addition to the baseline routine evaluations.

Treatment: Subjects are randomly assigned to treatment and will be treated for 14 days. A randomization visit will take place on Day 0 and an end-of-treatment visit will take place between day 14 and 16.

Follow-up: includes one visits. Approximately 28 days after the end of treatment. Eradication of H. Pylori will be confirmed by one of urea breath test，rapid urease test or helicobacter pylori stool antigen test.

• Study Type: Interventional
• Enrollment (Anticipated): 658
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Xijing Hosipital of Digestive Disease

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients who had failed H.pylori eradication therapies before.
2. Age between 18~70, both gender.
3. Patients who had failed H.pylori eradication therapies during last 2 years and stop the eradication therapies for at least 3 months.
4. Women are eligible if they are not pregnant or nursing, and if they are of childbearing potential they are required to use medically acceptable contraception for the duration of the study and 30 days thereafter.

Exclusion Criteria:

1. Patients are excluded if they have previously used tetracycline and furazolidone antibiotics to eradicate infection with H. pylori.
2. Contraindications to study drugs.
3. Substantial organ impairment, severe or unstable cardiopulmonary or endocrine disease.
4. Constant use of anti-ulcer drugs ( including taking proton-pump. inhibitors(PPI) within 2 weeks before the [13C] urea breath test), antibiotics or bismuth complexes (more than 3 times /1 month before screening).
5. Pregnant or lactating women.
6. Underwent upper gastrointestinal Surgery.
7. Patients with moderate or severe atypical hyperplasia or high-grade intraepithelial neoplasia.
8. have symptom of dysphagia.
9. Evidence of bleeding or iron efficiency anemia.
10. A history of malignancy.
11. Drug or alcohol abuse history in the past 1 year.
12. Systemic use of corticosteroids, non steroidal anti-inflammatory drugs, anticoagulants, platelet aggregation inhibitors (except the use of aspirin for less than 100 mg/d).
13. a person with a mental disorder.
14. Enrolled in other clinical trials in the past 3 months.
15. Refuse to sign informed consent.

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: High-dose esomeprazole and amoxicillin dual therapy; Esomeprazole 40 mg and amoxicillin 1000 mg by mouth，three time daily for 14 days	Drug: Esomeprazole; High-dose esomeprazole and amoxicillin dual therapy: given for 14 days at a dose of esomeprazole 40mg 1 tablet TID plus amoxicillin 500 mg 2 capsules TID; Other Names: Nexium; Drug: Amoxicillin; High-dose esomeprazole and amoxicillin dual therapy: given for 14 days at a dose of amoxicillin 500 mg 2 capsules TID plus esomeprazole 40mg 1 tablet TID; Other Names: Amoxy; Drug: Esomeprazole; Bismuth-containing quadruple therapy: given for 14 days at a dose of esomeprazole 40mg 1 tablet BID plus bismuth 110 mg 2 capsules BID，tetracycline 250mg 2 capsules TID and furazolidone 100mg 1 tablets BID; Other Names: Nexium
Active Comparator: Bismuth-containing quadruple therapy; Tetracycline 500mg three time daily for 14 days，furazolidone 100 mg, esomeprazole 40 mg, and Bismuth 220mg by mouth, twice daily for 14 days.	Drug: Esomeprazole; High-dose esomeprazole and amoxicillin dual therapy: given for 14 days at a dose of esomeprazole 40mg 1 tablet TID plus amoxicillin 500 mg 2 capsules TID; Other Names: Nexium; Drug: Esomeprazole; Bismuth-containing quadruple therapy: given for 14 days at a dose of esomeprazole 40mg 1 tablet BID plus bismuth 110 mg 2 capsules BID，tetracycline 250mg 2 capsules TID and furazolidone 100mg 1 tablets BID; Other Names: Nexium; Drug: Bismuth; Bismuth-containing quadruple therapy: given for 14 days at a dose of bismuth 110 mg 2 capsules BID plus esomeprazole 40 mg 1 tablets BID，tetracycline 250mg 2 capsules TID and furazolidone 100mg 1 tablets BID; Drug: Tetracycline; Bismuth-containing quadruple therapy:given for 14 days at a dose of tetracycline 250mg 2 capsules TID plus furazolidone 100mg 1 tablets BID，esomeprazole 40 mg 1 tablets BID and bismuth 110 mg 2 capsules BID; Drug: Furazolidone; Bismuth-containing quadruple therapy:given for 14 days at a dose of furazolidone 100mg 1 tablets BID plus tetracycline 250mg 2 capsules TID，esomeprazole 40 mg 1 tablets BID and bismuth 110 mg 2 capsules BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Helicobacter pylori eradication	The primary end point of this study is H.pylori eradication，established by negative [13C] urea breath test （DOB value below 3.9）28 days after the end of eradication	28 days after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events	Participants with Adverse Events as a Measure of Safety and Tolerability.The common side effects of the study include headache,dizziness,skin rash,other gastrointestinal disorders,pyrexia,cough and back pain.	14 days of treatment, and 28 days after treatment
symptoms effective rates	symptoms improvement rates Evaluation improvement rate of symptoms 2 weeks of treatment and 4 weeks after the end of treatment. Symptom improvement rate =#total score before treatment - total score after treatment#/total score before treatment x100%. Total score = frequency + severity.Frequency score is calculated by all the frequency of heartburn, reflux, abdominal pain, and flatulence, etc. Severity is accumulated by the degree of symptoms described above, which is divided to 4 degree as 0 presenting none, and 3 presenting most severe	14 days of treatment, and 28 days after treatment

Collaborators and Investigators

• Sponsor: Xijing Hospital of Digestive Diseases

Publications and helpful links

General Publications

• Bi H, Chen X, Chen Y, Zhao X, Wang S, Wang J, Lyu T, Han S, Lin T, Li M, Yuan D, Liu J, Shi Y. Efficacy and safety of high-dose esomeprazole-amoxicillin dual therapy for Helicobacter pylori rescue treatment: a multicenter, prospective, randomized, controlled trial. Chin Med J (Engl). 2022 Jul 20;135(14):1707-1715. doi: 10.1097/CM9.0000000000002289.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2020
• Primary Completion (Anticipated): December 20, 2021
• Study Completion (Anticipated): December 20, 2021

Study Registration Dates

• First Submitted: December 13, 2020
• First Submitted That Met QC Criteria: December 16, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): April 8, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Helicobacter pylori; High-dose dual therapy; Bismuth-combining quadruple therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Intestinal Diseases; Duodenal Diseases; Gastritis; Dyspepsia; Peptic Ulcer; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Monoamine Oxidase Inhibitors; Antacids; Anti-Infective Agents, Urinary; Renal Agents; Antitrichomonal Agents; Amoxicillin; Esomeprazole; Bismuth; Tetracycline; Furazolidone
• Other Study ID Numbers: KY20202114-F-1

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