Helicobacter Pylori Eradication With Berberine Quadruple Therapy Versus Bismuth-containing Quadruple Therapy

Sponsor

Xijing Hospital of Digestive Diseases (Other)

Overall Status

Completed

CT.gov ID

NCT02296021

Collaborator

(none)

612

Enrollment

Location

Arms

Duration (Months)

61.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims at evaluating efficacy and safety of berberine-containing quadruple therapy(berberine, esomeprazole, clarithromycin and amoxicillin) versus bismuth-containing quadruple therapy (bismuth,esomeprazole,clarithromycin and amoxicillin) in H. pylori eradication. It is hypothesized that berberine-containing quadruple therapy is non-inferior to bismuth-containing quadruple therapy. Patients with confirmed H. pylori positive status will be randomized to one of the treatments described above. At week 2 and 6 follow-up visits, a urea breath test(UBT) will be performed to confirm eradication.

Condition or Disease	Intervention/Treatment	Phase
Gastritis Peptic Ulcer Dyspepsia	Drug: Berberine Drug: Bismuth Drug: esomeprazole Drug: amoxicillin Drug: clarithromycin	Phase 4

Detailed Description

The study will include three phases: screening, treatment and follow-up. Screening: this phase will last a maximum of 28 days and subjects eligibility will be evaluated after informed consent signature. Endoscopy and Urea Breath 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 12 and 14.

Follow-up: includes two visits. approximately 14 days of treatment and 28 days after the end of treatment. Eradication of H. Pylori will be confirmed through urea breath test(UBT).

Study Design

Study Type:

Interventional

Actual Enrollment :

612 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Helicobacter Pylori Eradication With Berberine Hydrochloride,Esomeprazole,Amoxicillin and Clarithromycin Versus Bismuth,Esomeprazole,Amoxicillin,and Clarithromycin: a Randomized,Open-label, Non-inferiority, Phase Ⅳ Trail

Study Start Date :

Nov 1, 2014

Actual Primary Completion Date :

Sep 1, 2015

Actual Study Completion Date :

Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: berberine quadruple therapy Berberine 500 mg, esomeprazole 20 mg,amoxicillin 1000 mg, and clarithromycin 500 mg by mouth, twice daily for 14 days.	Drug: Berberine Berberine-containing quadruple therapy group: given for 14 days at a dose of berberine 100 mg 5 tablets BID, esomeprazole 20 mg BID, amoxicillin 500 mg 2 capsules BID, and clarithromycin 500 mg 1 tablet BID. Drug: esomeprazole Esmeprazole 20mg 1tablet BID plus amoxicillin 500 mg 2 capsules BID, clarithromycin 500 mg 1 tablet BID, and colloidal bismuth tartrate capsule 55 mg 4 capsules BID or berberine 100 mg 5 tablets BID as a dose given for bismuth-containing quadruple therapy or berberine-containing quadruple therapy. Other Names: Nexium Drug: amoxicillin Amoxicillin 500 mg 2 capsules BID plus esmeprazole 20mg 1tablet BID, clarithromycin 500 mg 1 tablet BID, and colloidal bismuth tartrate capsule 55 mg 4 capsules BID or berberine 100 mg 5 tablets BID as a dose given for bismuth-containing quadruple therapy or berberine-containing quadruple therapy. Other Names: Amoxy ( Uni-Amocin ) Drug: clarithromycin Clarithromycin 500 mg 1 tablet BID plus amoxicillin 500 mg 2 capsules BID, esmeprazole 20mg 1tablet BID, and colloidal bismuth tartrate capsule55 mg 4 capsules BID or berberine 100 mg 5 tablets BID as a dose given for bismuth-containing quadruple therapy or berberine-containing quadruple therapy.
Active Comparator: bismuth quadruple therapy Bismuth 220 mg, esomeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg by mouth,twice daily for 14 days.	Drug: Bismuth Bismuth-containing quadruple therapy group: given for 14 days at a dose of colloidal bismuth tartrate capsule 55 mg 4 capsules BID, esomeprazole 20 mg BID, amoxicillin 500 mg 2 capsules BID, and clarithromycin 500 mg 1 tablet BID. Other Names: Bitnal colloidal bismuth tartrate capsule Drug: esomeprazole Esmeprazole 20mg 1tablet BID plus amoxicillin 500 mg 2 capsules BID, clarithromycin 500 mg 1 tablet BID, and colloidal bismuth tartrate capsule 55 mg 4 capsules BID or berberine 100 mg 5 tablets BID as a dose given for bismuth-containing quadruple therapy or berberine-containing quadruple therapy. Other Names: Nexium Drug: amoxicillin Amoxicillin 500 mg 2 capsules BID plus esmeprazole 20mg 1tablet BID, clarithromycin 500 mg 1 tablet BID, and colloidal bismuth tartrate capsule 55 mg 4 capsules BID or berberine 100 mg 5 tablets BID as a dose given for bismuth-containing quadruple therapy or berberine-containing quadruple therapy. Other Names: Amoxy ( Uni-Amocin ) Drug: clarithromycin Clarithromycin 500 mg 1 tablet BID plus amoxicillin 500 mg 2 capsules BID, esmeprazole 20mg 1tablet BID, and colloidal bismuth tartrate capsule55 mg 4 capsules BID or berberine 100 mg 5 tablets BID as a dose given for bismuth-containing quadruple therapy or berberine-containing quadruple therapy.

Arm

Intervention/Treatment

Experimental: berberine quadruple therapy

Berberine 500 mg, esomeprazole 20 mg,amoxicillin 1000 mg, and clarithromycin 500 mg by mouth, twice daily for 14 days.

Drug: Berberine

Berberine-containing quadruple therapy group: given for 14 days at a dose of berberine 100 mg 5 tablets BID, esomeprazole 20 mg BID, amoxicillin 500 mg 2 capsules BID, and clarithromycin 500 mg 1 tablet BID.

Drug: esomeprazole

Esmeprazole 20mg 1tablet BID plus amoxicillin 500 mg 2 capsules BID, clarithromycin 500 mg 1 tablet BID, and colloidal bismuth tartrate capsule 55 mg 4 capsules BID or berberine 100 mg 5 tablets BID as a dose given for bismuth-containing quadruple therapy or berberine-containing quadruple therapy.

Other Names:

Nexium

Drug: amoxicillin

Amoxicillin 500 mg 2 capsules BID plus esmeprazole 20mg 1tablet BID, clarithromycin 500 mg 1 tablet BID, and colloidal bismuth tartrate capsule 55 mg 4 capsules BID or berberine 100 mg 5 tablets BID as a dose given for bismuth-containing quadruple therapy or berberine-containing quadruple therapy.

Other Names:

Amoxy ( Uni-Amocin )

Drug: clarithromycin

Clarithromycin 500 mg 1 tablet BID plus amoxicillin 500 mg 2 capsules BID, esmeprazole 20mg 1tablet BID, and colloidal bismuth tartrate capsule55 mg 4 capsules BID or berberine 100 mg 5 tablets BID as a dose given for bismuth-containing quadruple therapy or berberine-containing quadruple therapy.

Active Comparator: bismuth quadruple therapy

Bismuth 220 mg, esomeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg by mouth,twice daily for 14 days.

Drug: Bismuth

Bismuth-containing quadruple therapy group: given for 14 days at a dose of colloidal bismuth tartrate capsule 55 mg 4 capsules BID, esomeprazole 20 mg BID, amoxicillin 500 mg 2 capsules BID, and clarithromycin 500 mg 1 tablet BID.

Other Names:

Bitnal

colloidal bismuth tartrate capsule

Drug: esomeprazole

Other Names:

Nexium

Drug: amoxicillin

Other Names:

Amoxy ( Uni-Amocin )

Drug: clarithromycin

Outcome Measures

Primary Outcome Measures

helicobacter pylori eradication [28 days after treatment]
The primary end point of this study is H.pylori eradication,established by negative [13C] urea breath test 28 days after the end of eradication.

Secondary Outcome Measures

symptoms effective rates [14 days of treatment, and 28 days after treatment]
Evaluation effective rate of symptoms 2 weeks of treatment and 4 weeks after the end of treatment. Symptom effective rate =（total score before treatment - total score after treatment）/total score before treatment x 100%. Total score = frequency + severity. Frequency score is calculated by all the frequency of heartburn,reflux,abdominal pain,and flatulence. 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.
adverse events [14 days of treatment, and 28 days after treatment]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age between 18~70,both gender.
Patients with upper gastrointestinal symptoms and with documented H.pylori infection.
Patients are willing to receive eradication treatment.
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:

Patients are excluded if they have previously used antibiotics to eradicate adequately recorded infection with H. pylori.
Contraindications to study drugs.
Substantial organ impairment, severe or unstable cardiopulmonary or endocrine disease.
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)
Pregnant or lactating women.
Underwent upper gastrointestinal Surgery.
Patients with Barrett esophageal or highly atypical hyperplasia, have symptom of dysphagia.
Evidence of bleeding or iron eficiency anemia.
A history of malignancy.
Drug or alcohol abuse history in the past 1 year.
Systemic use of corticosteroids, non steroidal anti-inflammatory drugs, anticoagulants, platelet aggregation inhibitors (except the use of aspirin for less than 100 mg/d).
Enrolled in other clinical trials in the past 3 months.