Bismuth-containing Quadruple Therapy for Helicobacter Pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days

Bismuth-containing Quadruple Therapy for Helicobacter Pylori Eradication: A Multicenter Randomized Clinical Trial of 10 and 14 Days

The researchers collect treatment-naive H.pylori-positive patients from the outpatient clinic. The subjects were randomized to receive a 10-day or 14-day course of quadruple eradication therapy. 6-8 weeks after treatment, the subjects will re-take the 13C-urea breath test. Calculate the eradication rates, adverse reaction rates, patient compliance and cost-effectiveness index of each group.

Study Overview

• Status: Not yet recruiting
• Conditions: Helicobacter Pylori Infection
• Intervention / Treatment: Drug: Amoxicillin; Drug: Clarithromycin; Drug: Tetracycline; Drug: Metronidazole; Drug: Bismuth Potassium Citrate; Drug: Colloidal Bismuth Pectin; Drug: Vonoprazan fumarate

Detailed Description

The researchers collect treatment-naive H.pylori-positive patients from the outpatient clinic. If the subject meets the selection criteria but not the exclusion criteria, and signs an informed consent form, the researchers randomized the subjects in groups: subjects received a 10-day or 14-day course of bismuth-containing quadruple eradication therapy. The medication of groups are as follows. 6-8 weeks after the eradication treatment, the subjects will review the 13C-urea breath test, and the researcher records the results.

After all subjects were tested, the eradication rates, adverse reaction rates, patient compliance and cost-effectiveness index of each group were calculated.

According to the course of treatment, it is randomized into a 10-day treatment group and a 14-day treatment group. The two groups of bismuth quadruple regimens are the same, as follows:

Option 1: Amoxicillin + Clarithromycin + Bismuth + Vonoprazan fumarate Option 2: Amoxicillin + Tetracycline + Bismuth + Vonoprazan fumarate Option 3: Amoxicillin + Metronidazole + Bismuth + Vonoprazan fumarate Three options are selected according to the hospital's situation.

• Study Type: Interventional
• Enrollment (Anticipated): 1300
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 257000
      • Qilu hosipital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged 18-65.
• Patients with H.pylori infection (Positive for any of the following: H.pylori culture, histopathology test, rapid urease test, 13C/14C-urea breath test, stool H.pylori antigen test).
• Patients whose birth place and residence within five years of birth are Shandong Province.
• Patients who have never received H. pylori eradication treatment.

Exclusion Criteria:

• Patients with serious underlying diseases, such as liver insufficiency (Aspartate aminotransferase or alanine aminotransferase greater than 3 times the normal value), renal insufficiency (Cr≥2.0mg/dL or glomerular filtration rate <50 ml/min), immunosuppression, malignant tumors, Coronary heart disease or coronary artery stenosis ≥75%.
• Patients who are pregnant or lactating or unwilling to take contraceptive measures during the trial.
• Patients with active gastrointestinal bleeding.
• Patients with a history of upper gastrointestinal surgery.
• Patients allergic to treatment drugs.
• Patients with medication history of bismuth agents, antibiotics, proton pump inhibitor and other drugs within 4 weeks
• Patients with other behaviors that may increase the risk of illness, such as alcohol and drug abuse
• Patients whose current residence is not in Shandong Province.
• Patients whose re-check 13C/14C-urea breath test is negative before the start of the test.
• Patients who are unwilling or incapable to provide informed consents.

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: 10-day treatment group; Use the following drug combination option for 10 days. Option 1: Amoxicillin + Clarithromycin + Bismuth + Vonoprazan fumarate Option 2: Amoxicillin + Tetracycline + Bismuth + Vonoprazan fumarate Option 3: Amoxicillin + Metronidazole + Bismuth + Vonoprazan fumarate Three options are selected according to the hospital's situation. The dosage of each drug is: Amoxicillin (Amoxicillin, United Laboratories Co., Ltd.) 1000mg bid Clarithromycin (Klacid, Abbott S.r.l) 500mg bid Tetracycline 500mg qid Metronidazole400mg qid Bismuth Potassium Citrate (Livzon Pharmaceutical Group Inc.) 220mg bid Colloidal Bismuth Pectin (North China Pharmaceutical Co., Ltd.) 200mg bid Vonoprazan fumarate (VOCINTI, Takeda Pharmaceutical Company Limited, Hikari Plant) 20mg bid	Drug: Amoxicillin; Use according to the drug combination options selected by each center.; Drug: Clarithromycin; Use according to the drug combination options selected by each center.; Drug: Tetracycline; Use according to the drug combination options selected by each center.; Drug: Metronidazole; Use according to the drug combination options selected by each center.; Drug: Bismuth Potassium Citrate; Use according to the drug combination options selected by each center.; Drug: Colloidal Bismuth Pectin; Use according to the drug combination options selected by each center.; Drug: Vonoprazan fumarate; Use according to the drug combination options selected by each center.
Active Comparator: 14-day treatment group; Use the following drug combination option for 14 days. Option 1: Amoxicillin + Clarithromycin + Bismuth + Vonoprazan fumarate Option 2: Amoxicillin + Tetracycline + Bismuth + Vonoprazan fumarate Option 3: Amoxicillin + Metronidazole + Bismuth + Vonoprazan fumarate Three options are selected according to the hospital's situation. The dosage of each drug is: Amoxicillin (Amoxicillin, United Laboratories Co., Ltd.) 1000mg bid Clarithromycin (Klacid, Abbott S.r.l) 500mg bid Tetracycline 500mg qid Metronidazole400mg qid Bismuth Potassium Citrate (Livzon Pharmaceutical Group Inc.) 220mg bid Colloidal Bismuth Pectin (North China Pharmaceutical Co., Ltd.) 200mg bid Vonoprazan fumarate (VOCINTI, Takeda Pharmaceutical Company Limited, Hikari Plant) 20mg bid	Drug: Amoxicillin; Use according to the drug combination options selected by each center.; Drug: Clarithromycin; Use according to the drug combination options selected by each center.; Drug: Tetracycline; Use according to the drug combination options selected by each center.; Drug: Metronidazole; Use according to the drug combination options selected by each center.; Drug: Bismuth Potassium Citrate; Use according to the drug combination options selected by each center.; Drug: Colloidal Bismuth Pectin; Use according to the drug combination options selected by each center.; Drug: Vonoprazan fumarate; Use according to the drug combination options selected by each center.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eradication rate	Both intention to treat (ITT) and per-protocol (PP) analyses will be used for the assessment of the eradication rates of Helicobacter pylori infections in two groups. The ITT analysis includes all randomly assigned patients who take at least one dose of the study medications. The PP analysis is limited to patients who take over 90% of the study medications and complete follow-up.	Immediately after follow-up check.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of adverse reactions	Rate of adverse reactions	Immediately after follow-up check.
Patient compliance	Good compliance is defined as the actual dosage is within the range of 80%-100% of the dosage that should be taken.	Immediately after follow-up check.
Cost-effectiveness index	Ratio of costs to effectiveness	Immediately after follow-up check.

Collaborators and Investigators

• Sponsor: Shandong University
• Collaborators: Qilu Hospital of Shandong University; The Affiliated Hospital of Qingdao University; The People's Hospital of Guangrao; Weihai Municipal Hospital; Shandong Provincial Third Hospital; Taian City Central Hospital; Jining No.2 People's Hospital; Maternity and Child Care Health Center of Dezhou; Zoucheng People's Hospital; Heze Municipal 3rd people's hospital; Yuncheng Chengxin Hospital; Peking University Care Luzhong Hospital; Qihe County City Hospital; Weifang People's Hospital; Shandong Electric Power Central Hospital

Publications and helpful links

General Publications

• Liou JM, Malfertheiner P, Lee YC, Sheu BS, Sugano K, Cheng HC, Yeoh KG, Hsu PI, Goh KL, Mahachai V, Gotoda T, Chang WL, Chen MJ, Chiang TH, Chen CC, Wu CY, Leow AH, Wu JY, Wu DC, Hong TC, Lu H, Yamaoka Y, Megraud F, Chan FKL, Sung JJ, Lin JT, Graham DY, Wu MS, El-Omar EM; Asian Pacific Alliance on Helicobacter and Microbiota (APAHAM). Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus. Gut. 2020 Dec;69(12):2093-2112. doi: 10.1136/gutjnl-2020-322368. Epub 2020 Oct 1.
• Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, Malfertheiner P, Graham DY, Wong VWS, Wu JCY, Chan FKL, Sung JJY, Kaplan GG, Ng SC. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology. 2017 Aug;153(2):420-429. doi: 10.1053/j.gastro.2017.04.022. Epub 2017 Apr 27.
• Liu WZ, Xie Y, Lu H, Cheng H, Zeng ZR, Zhou LY, Chen Y, Wang JB, Du YQ, Lu NH; Chinese Society of Gastroenterology, Chinese Study Group on Helicobacter pylori and Peptic Ulcer. Fifth Chinese National Consensus Report on the management of Helicobacter pylori infection. Helicobacter. 2018 Apr;23(2):e12475. doi: 10.1111/hel.12475. Epub 2018 Mar 7.
• Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ, Axon AT, Bazzoli F, Gasbarrini A, Atherton J, Graham DY, Hunt R, Moayyedi P, Rokkas T, Rugge M, Selgrad M, Suerbaum S, Sugano K, El-Omar EM; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017 Jan;66(1):6-30. doi: 10.1136/gutjnl-2016-312288. Epub 2016 Oct 5.
• Dore MP, Farina V, Cuccu M, Mameli L, Massarelli G, Graham DY. Twice-a-day bismuth-containing quadruple therapy for Helicobacter pylori eradication: a randomized trial of 10 and 14 days. Helicobacter. 2011 Aug;16(4):295-300. doi: 10.1111/j.1523-5378.2011.00857.x.
• Rowland M, Daly L, Vaughan M, Higgins A, Bourke B, Drumm B. Age-specific incidence of Helicobacter pylori. Gastroenterology. 2006 Jan;130(1):65-72; quiz 211. doi: 10.1053/j.gastro.2005.11.004.
• O'Ryan ML, Rabello M, Cortes H, Lucero Y, Pena A, Torres JP. Dynamics of Helicobacter pylori detection in stools during the first 5 years of life in Chile, a rapidly developing country. Pediatr Infect Dis J. 2013 Feb;32(2):99-103. doi: 10.1097/INF.0b013e318278b929.
• Qiao C, Li Y, Liu J, Ji C, Qu J, Hu J, Ji R, Wan M, Lin B, Lin M, Qi Q, Zuo X, Li Y. Clarithromycin versus furazolidone for naive Helicobacter pylori infected patients in a high clarithromycin resistance area. J Gastroenterol Hepatol. 2021 Sep;36(9):2383-2388. doi: 10.1111/jgh.15468. Epub 2021 Mar 10.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: May 24, 2021
• First Submitted That Met QC Criteria: May 24, 2021
• First Posted (Actual): May 25, 2021

Study Record Updates

• Last Update Posted (Actual): May 25, 2021
• Last Update Submitted That Met QC Criteria: May 24, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Helicobacter pylori; Bismuth-containing quadruple regimen
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Natriuretic Agents; Anti-Bacterial Agents; Diuretics; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Respiratory System Agents; Antiprotozoal Agents; Antiparasitic Agents; Expectorants; Antacids; Metronidazole; Amoxicillin; Clarithromycin; Bismuth; Tetracycline; Potassium Citrate
• Other Study ID Numbers: 2021-SDU-QILU-G001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No