A Multi-center Study for Eradication of Helicobacter Pylori With Triple Therapy Using Clarithromycin

A Multi-center Study for Eradication of Helicobacter Pylori With Triple Therapy Based on Accurate Susceptibility Testing of Clarithromycin

As the resistant rate of the Helicobacter pylori to some common antibiotics was rising，the eradication rate of the Helicobacter pylori with the standard triple therapy failed to exceed 70% in China，and had to drop out of the first-line treatment recommendations. However, with the increase of treatment time, patients burden, adverse reactions of antibiotics or proton pump inhibitor (PPI) will also increase. Resistance to clarithromycin is the major cause of the failure to eradicate Helicobacter pylori. But, in terms of population, there are still more than 70% of the patients with clarithromycin sensitive. Under the guidance with susceptibility test，7-day standard triple therapy could be used. In this study, investigators will select the patients with infection of H. pylori and with clarithromycin sensitive. Eradication of Helicobacter pylori with triple therapy based on accurate susceptibility testing of clarithromycin will be studied. The treatment time will be assigned into 7 days,10 days and 14 days groups. Then, investigators will perform a sequencing for failed treatment patients in groups, such as drug resistance gene mutation, phenotype and genotype. Finally, investigators will compare the differences between the patients with triple therapy and traditional quadruple therapy.The incidence of adverse effects in the eradicate treatment will reduce at least 10% and avoid patients' unnecessary economic losses at least 400RMB per person.

Study Overview

• Status: Unknown
• Conditions: Gastritis
• Intervention / Treatment: Device: The results of clarithromycin susceptibility test of H. pylori isolates; Device: Computer generated random number, randomly assigned into groups; Device: The result of 13C-urea breath test of patient in 7days/10days/14days treatment groups

• Study Type: Interventional
• Enrollment (Anticipated): 672
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: zhang hong Li, doctor; Email: smyylhz@163.com

Study Locations

• China
  • Zhejiang
    • Taizhou, Zhejiang, China, 317199
      • Recruiting
      • Sanmen People's Hospital
      • Contact: zhang hong Li, doctor; Email: smyylhz@163.com

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. Age 18~70 years old, male or female, the first eradication therapy of H. pylori infection patients.
2. Symptoms of abdominal pain, bloating, acid efflux, belching, nausea, vomiting, heartburn, chest pain, vomiting, melena, etc.
3. Unused antibiotics, bismuth, H2 receptor antagonists or PPI by nearly 4 weeks
4. 13C-labelled urea breath test positive.
5. Agreed to Helicobacter pylori culture and sensitivity testing taken by endoscopy gastric biopsy specimens,and the result of culture was positive.
6. Agreed to Helicobacter pylori eradication therapy and cooperate with the eradication efficacy follow-up survey.

Exclusion Criteria:

1. Severe heart, liver, kidney dysfunction.
2. Pregnant or lactating women.
3. Complications of bleeding, perforation, pyloric obstruction, cancer.
4. Within 3 months before with the drugs involved in other drugs research.
5. Esophageal,gastrointestinal surgery history.
6. Patients can not properly express their complaints,such as psychosis, severe neurosis.
7. Taking NSIAD or alcohol abusers.
8. Allergic to amoxicillin or clarithromycin tested by susceptibility testing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clarithromycin resistance group; Patients who are resistant to clarithromycin in susceptibility test were classified into clarithromycin resistance group.	Device: The results of clarithromycin susceptibility test of H. pylori isolates; According to the results of antibiotic susceptible testing, patients who were resistant to clarithromycin were belonged into clarithromycin resistance group.Patients who were sensitive to clarithromycin were belonged into the 7days/10days/14days treatment groups.
Experimental: 7 days Successful treatment; The successful treatment of H. pylori group were treatment successful patients after the 7days standardized treatment.	Device: The results of clarithromycin susceptibility test of H. pylori isolates; According to the results of antibiotic susceptible testing, patients who were resistant to clarithromycin were belonged into clarithromycin resistance group.Patients who were sensitive to clarithromycin were belonged into the 7days/10days/14days treatment groups.; Device: Computer generated random number, randomly assigned into groups; The patients with clarithromycin sensitive. Computer generated random number,randomly assigned into 7days/10days/14days treatment groups.; Device: The result of 13C-urea breath test of patient in 7days/10days/14days treatment groups; The intervention focused on the results from the result of 13C-urea breath test at 8 weeks after treatment in patients. All patients were taking 75mg 13C-urea and analysis with a modified isotope ratio mass spectrometer to determine the 13CO2 content.The successful treatment groups were patients with negative in 13C-urea breath tests.The failed treatment of H. pylori groups were patients with positive in 13C-urea breath tests after the standardized triple therapy treatment.
Experimental: 7 days failed treatment; The failed treatment of H. pylori group were treatment failure patients after the 7days standardized treatment.	Device: The results of clarithromycin susceptibility test of H. pylori isolates; According to the results of antibiotic susceptible testing, patients who were resistant to clarithromycin were belonged into clarithromycin resistance group.Patients who were sensitive to clarithromycin were belonged into the 7days/10days/14days treatment groups.; Device: Computer generated random number, randomly assigned into groups; The patients with clarithromycin sensitive. Computer generated random number,randomly assigned into 7days/10days/14days treatment groups.; Device: The result of 13C-urea breath test of patient in 7days/10days/14days treatment groups; The intervention focused on the results from the result of 13C-urea breath test at 8 weeks after treatment in patients. All patients were taking 75mg 13C-urea and analysis with a modified isotope ratio mass spectrometer to determine the 13CO2 content.The successful treatment groups were patients with negative in 13C-urea breath tests.The failed treatment of H. pylori groups were patients with positive in 13C-urea breath tests after the standardized triple therapy treatment.
Experimental: 10 days Successful treatment; The successful treatment of H. pylori group were treatment successful patients after the 10days standardized treatment.	Device: The results of clarithromycin susceptibility test of H. pylori isolates; According to the results of antibiotic susceptible testing, patients who were resistant to clarithromycin were belonged into clarithromycin resistance group.Patients who were sensitive to clarithromycin were belonged into the 7days/10days/14days treatment groups.; Device: Computer generated random number, randomly assigned into groups; The patients with clarithromycin sensitive. Computer generated random number,randomly assigned into 7days/10days/14days treatment groups.; Device: The result of 13C-urea breath test of patient in 7days/10days/14days treatment groups; The intervention focused on the results from the result of 13C-urea breath test at 8 weeks after treatment in patients. All patients were taking 75mg 13C-urea and analysis with a modified isotope ratio mass spectrometer to determine the 13CO2 content.The successful treatment groups were patients with negative in 13C-urea breath tests.The failed treatment of H. pylori groups were patients with positive in 13C-urea breath tests after the standardized triple therapy treatment.
Experimental: 10 days failed treatment; The failed treatment of H. pylori group were treatment failure patients after the 10days standardized treatment.	Device: The results of clarithromycin susceptibility test of H. pylori isolates; According to the results of antibiotic susceptible testing, patients who were resistant to clarithromycin were belonged into clarithromycin resistance group.Patients who were sensitive to clarithromycin were belonged into the 7days/10days/14days treatment groups.; Device: Computer generated random number, randomly assigned into groups; The patients with clarithromycin sensitive. Computer generated random number,randomly assigned into 7days/10days/14days treatment groups.; Device: The result of 13C-urea breath test of patient in 7days/10days/14days treatment groups; The intervention focused on the results from the result of 13C-urea breath test at 8 weeks after treatment in patients. All patients were taking 75mg 13C-urea and analysis with a modified isotope ratio mass spectrometer to determine the 13CO2 content.The successful treatment groups were patients with negative in 13C-urea breath tests.The failed treatment of H. pylori groups were patients with positive in 13C-urea breath tests after the standardized triple therapy treatment.
Experimental: 14 days Successful treatment; The successful treatment of H. pylori group were treatment successful patients after the 14days standardized treatment.	Device: The results of clarithromycin susceptibility test of H. pylori isolates; According to the results of antibiotic susceptible testing, patients who were resistant to clarithromycin were belonged into clarithromycin resistance group.Patients who were sensitive to clarithromycin were belonged into the 7days/10days/14days treatment groups.; Device: Computer generated random number, randomly assigned into groups; The patients with clarithromycin sensitive. Computer generated random number,randomly assigned into 7days/10days/14days treatment groups.; Device: The result of 13C-urea breath test of patient in 7days/10days/14days treatment groups; The intervention focused on the results from the result of 13C-urea breath test at 8 weeks after treatment in patients. All patients were taking 75mg 13C-urea and analysis with a modified isotope ratio mass spectrometer to determine the 13CO2 content.The successful treatment groups were patients with negative in 13C-urea breath tests.The failed treatment of H. pylori groups were patients with positive in 13C-urea breath tests after the standardized triple therapy treatment.
Experimental: 14 days failed treatment; The failed treatment of H. pylori group were treatment failure patients after the 14days standardized treatment.	Device: The results of clarithromycin susceptibility test of H. pylori isolates; According to the results of antibiotic susceptible testing, patients who were resistant to clarithromycin were belonged into clarithromycin resistance group.Patients who were sensitive to clarithromycin were belonged into the 7days/10days/14days treatment groups.; Device: Computer generated random number, randomly assigned into groups; The patients with clarithromycin sensitive. Computer generated random number,randomly assigned into 7days/10days/14days treatment groups.; Device: The result of 13C-urea breath test of patient in 7days/10days/14days treatment groups; The intervention focused on the results from the result of 13C-urea breath test at 8 weeks after treatment in patients. All patients were taking 75mg 13C-urea and analysis with a modified isotope ratio mass spectrometer to determine the 13CO2 content.The successful treatment groups were patients with negative in 13C-urea breath tests.The failed treatment of H. pylori groups were patients with positive in 13C-urea breath tests after the standardized triple therapy treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The accurate determination of clarithromycin susceptibility.	Assess bacterial susceptibility to antibiotics using the agar diffusion method. The Resistance point of clarithromycin was divided into 0.125μg/ml,0.25μg/ml,0.5μg/ml and 1μg/ml.Test clarithromycin resistance of Helicobacter pylori for patients.	2 years
Establish individualized precision triple therapy based on minimal inhibitory concentration.	Based on the clarithromycin accurate susceptibility，pinpoint different courses of triple treatment therapy targeted to different people based on minimal inhibitory concentration of clarithromycin.	2.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of adverse effects	Drugs targeted, it could reduce the intake of antibiotics for patients.The incidence of adverse effects in the eradicate treatment will reduce. Avoid patients' unnecessary economic losses.	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of mixed infection and CYP2C19 genotype on eradication rate for Helicobacter pylori with triple therapy using clarithromycin.	Investigators will perform a sequencing for failed treatment patients in groups, such as drug resistance gene mutation,and CYP2C19 genotype. Evaluating the impact of mixed infection and CYP2C19 genotype on eradication rate for Helicobacter pylori with triple therapy.	3 years

Collaborators and Investigators

• Sponsor: Sanmen People's Hospital
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Wenzhou Central Hospital; Taizhou Hospital; Centers for Disease Control and Prevention, China; Zhiyuan Medical Inspection Institute; The first people Hospital of Wenling; The first people Hospital of Yongkang

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: August 23, 2016
• First Submitted That Met QC Criteria: October 4, 2016
• First Posted (Estimate): October 5, 2016

Study Record Updates

• Last Update Posted (Actual): February 19, 2019
• Last Update Submitted That Met QC Criteria: February 16, 2019
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Helicobacter pylori; Sequencing; Antibiotic resistance
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Gastritis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Clarithromycin
• Other Study ID Numbers: SanmenPH