Helicobacter Pylori Eradication With Berberine Quadruple Therapy Versus Clarithromycin Quadruple Therapy

• ClinicalTrials.gov Identifier: NCT02633930
• Recruitment Status: Completed
• First Posted: December 17, 2015
• Last Update Posted: January 18, 2017
• Sponsor: Xijing Hospital of Digestive Diseases
• Information provided by (Responsible Party): Yongquan Shi, Xijing Hospital of Digestive Diseases

Study Description

Brief Summary:

This study aims at evaluating efficacy and safety of berberine-containing quadruple therapy(berberine, lansoprazole, bismuth and amoxicillin) versus clarithromycin-containing quadruple therapy (clarithromycin,lansoprazole, bismuth and amoxicillin) in H. pylori eradication. It is hypothesized that berberine-containing quadruple therapy is non-inferior to clarithromycin-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: clarithromycin; Drug: Bismuth; Drug: Lansoprazole; Drug: amoxicillin	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 (Clinical Trial)
• Actual Enrollment: 566 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Helicobacter Pylori Eradication With Berberine Hydrochloride, Lansoprazole, Amoxicillin and Bismuth Versus Clarithromycin Bismuth, Lansoprazole and Amoxicillin: A Randomized, Open-label, Non-inferiority, Phase Ⅳ Trial
• Study Start Date: December 2015
• Actual Primary Completion Date: June 2016
• Actual Study Completion Date: August 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: berberine quadruple therapy; Berberine 300 mg, three times daily for 14 days,lansoprazole 30 mg,amoxicillin 1000 mg, and Bismuth 220 mg by mouth, twice daily for 14 days.	Drug: Berberine; : given for 14 days at a dose of berberine 100 mg 3 tablets TID, lansoprazole 30 mg BID, amoxicillin 500 mg 2 capsules BID, and colloidal bismuth tartrate capsule55 mg 4 capsules BID; Drug: Bismuth; Bismuth:given for 14 days at a dose of colloidal bismuth tartrate capsule 55 mg 4 capsules BID, lansoprazole30 mg BID, amoxicillin 500 mg 2 capsules BID, and clarithromycin 500 mg 1 tablet BID or given for 14 days at a dose of colloidal bismuth tartrate capsule 55 mg 4 capsules BID, lansoprazole30 mg BID, amoxicillin 500 mg 2 capsules BID, and berberine 100 mg 3 tablet TID; Other Name: Bitnal; Drug: Lansoprazole; Lansoprazole 30mg 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 3 tablets TID given to berberine-containing quadruple therapy group or clarithromycin-containing quadruple therapy group; Other Name: Takepron; Drug: amoxicillin; Amoxicillin 500 mg 2 capsules BID plus lansoprazole 30mg 1tablet BID, clarithromycin 500 mg 1 tablet BID, and colloidal bismuth tartrate capsule 55 mg 4 capsules BID or berberine 100 mg 3 tablets TID as a dose given for clarithromycin-containing quadruple therapy or berberine-containing quadruple therapy.; Other Name: Amoxy ( Uni-Amocin )
Active Comparator: clarithromycin quadruple therapy; Bismuth 220 mg, lansoprazole30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg by mouth,twice daily for 14 days.	Drug: clarithromycin; Clarithromycin-containing quadruple therapy group 500 mg 1 tablet BID plus amoxicillin 500 mg 2 capsules BID, lansoprazole 30mg 1tablet BID, and colloidal bismuth tartrate capsule55 mg 4 capsules BID.; Drug: Bismuth; Bismuth:given for 14 days at a dose of colloidal bismuth tartrate capsule 55 mg 4 capsules BID, lansoprazole30 mg BID, amoxicillin 500 mg 2 capsules BID, and clarithromycin 500 mg 1 tablet BID or given for 14 days at a dose of colloidal bismuth tartrate capsule 55 mg 4 capsules BID, lansoprazole30 mg BID, amoxicillin 500 mg 2 capsules BID, and berberine 100 mg 3 tablet TID; Other Name: Bitnal; Drug: Lansoprazole; Lansoprazole 30mg 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 3 tablets TID given to berberine-containing quadruple therapy group or clarithromycin-containing quadruple therapy group; Other Name: Takepron; Drug: amoxicillin; Amoxicillin 500 mg 2 capsules BID plus lansoprazole 30mg 1tablet BID, clarithromycin 500 mg 1 tablet BID, and colloidal bismuth tartrate capsule 55 mg 4 capsules BID or berberine 100 mg 3 tablets TID as a dose given for clarithromycin-containing quadruple therapy or berberine-containing quadruple therapy.; Other Name: Amoxy ( Uni-Amocin )

Outcome Measures

Primary Outcome Measures :

1. helicobacter pylori eradication [ Time Frame: 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 :

1. symptoms effective rates [ Time Frame: 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

2. adverse events [ Time Frame: 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

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

Criteria

Inclusion Criteria:

1. Age between 18~70,both gender.
2. Patients with upper gastrointestinal symptoms and with documented H.pylori infection.
3. Patients are willing to receive eradication treatment.
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 antibiotics to eradicate adequately recorded 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 Barrett esophageal or highly atypical hyperplasia, have symptom of dysphagia.
8. Evidence of bleeding or iron efficiency anemia.
9. A history of malignancy.
10. Drug or alcohol abuse history in the past 1 year.
11. Systemic use of corticosteroids, non steroidal anti-inflammatory drugs, anticoagulants, platelet aggregation inhibitors (except the use of aspirin for less than 100 mg/d).
12. Enrolled in other clinical trials in the past 3 months.

Contacts and Locations

Locations

China, Shanxi

Xijing Hospital of Digestive Diseases

Xi'an, Shanxi, China, 710032

Xijing Hospital of Digestive Disease

Xi'an, Shanxi, China, 710032

Sponsors and Collaborators

Xijing Hospital of Digestive Diseases

Investigators

• Principal Investigator: Yongquan Shi, Ph. D; Xijing Hospital

More Information

• Responsible Party: Yongquan Shi, Doctor of Xijing Hospital of Digestive Diseases,Principal investagator,Clinical professor, Xijing Hospital of Digestive Diseases
• ClinicalTrials.gov Identifier: NCT02633930 History of Changes
• Other Study ID Numbers: KY20151203-2
• First Posted: December 17, 2015
• Last Update Posted: January 18, 2017
• Last Verified: January 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Yongquan Shi, Xijing Hospital of Digestive Diseases:

helicobacter pylori; berberine-containing quadruple therapy; clarithromycin-containing quadruple therapy

Additional relevant MeSH terms:

Peptic Ulcer; Gastritis; Dyspepsia; Signs and Symptoms, Digestive; Signs and Symptoms; Duodenal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Stomach Diseases; Gastroenteritis; Amoxicillin; Clarithromycin; Lansoprazole; Dexlansoprazole; Bismuth; Anti-Bacterial Agents; Anti-Infective Agents; Protein Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Anti-Ulcer Agents; Gastrointestinal Agents; Proton Pump Inhibitors; Antacids