Clinical trial NCT05431075: Bismuth-containing Quadruple Therapy for Helicobacter Pylori First-line Treatment of Different Tetracycline Doses
Official title: Bismuth-containing Quadruple Therapy for Helicobacter Pylori First-line Treatment: A Multicenter Randomized Clinical Trial of Different Tetracycline Doses and Frequencies.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Helicobacter Pylori Infection
Keywords: Helicobacter pylori
tetracycline
Bismuth-containing quadruple regimen
Lead sponsor: Shandong University
Sponsor class: OTHER
Collaborators: name: Peking University Care Luzhong Hospital
name: Yuncheng Traditional Chinese Medicine Hospital
name: Taierzhuang District People's Hospital
name: Zhengzhou Central Hospital
name: Zibo Central Hospital
First posted: 2022-06-24
Enrollment: 406
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This trial is a multi-center, open-label, non-inferiority, randomized controlled trial.
Primary purpose: TREATMENT

Brief summary: The researchers collect treatment-naive H.pylori-positive patients from the outpatient clinic. The subjects were randomized to receive a dose and frequency of tetracycline 500mg tid or qid of bismuth 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.

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 dose and frequency of tetracycline 500mg tid or qid 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 tid treatment group and a qid treatment group. The two groups of bismuth quadruple regimens are the same, as follows:

Tid group: Amoxicillin 1000mg bid+ Tetracycline 500mg tid+ Bismuth + Esomeprazole 20mg bid Qid group: Amoxicillin 1000mg bid+ Tetracycline 500mg qid+ Bismuth + Esomeprazole 20mg bid

Eligibility criteria: Inclusion Criteria:

* Patients aged 18-70.
* Patients with H.pylori infection (Positive for rapid urease test or 13C/14C-urea breath test).
* 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 1.5 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 who are unwilling or incapable to provide informed consents.

Primary outcomes:
measure: Eradication rate
timeFrame: Immediately after follow-up check.
Secondary outcomes:
measure: Rate of adverse reactions
timeFrame: Immediately after follow-up check.
measure: Patient compliance
timeFrame: Immediately after follow-up check.
measure: Cost-effectiveness index
timeFrame: Immediately after follow-up check.
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Zhengzhou Central Hospital
state: Henan
city: Jinan
country: China
facility: Qilu hosipital
state: Shandong
city: Taierzhuang
country: China
facility: Taierzhuang District People's Hospital
state: Shandong
city: Yuncheng
country: China
facility: Yuncheng Hospital of Traditional Chinese Medicine
state: Shandong
city: Zibo
country: China
facility: PKUCare Luzhong Hospital
state: Shandong
city: Zibo
country: China
facility: Zibo Central Hospital
state: Shandong
Study officials:
affiliation: Qilu Hospital of Shandong University
name: Xiuli Zuo, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: Ding SZ, Du YQ, Lu H, Wang WH, Cheng H, Chen SY, Chen MH, Chen WC, Chen Y, Fang JY, Gao HJ, Guo MZ, Han Y, Hou XH, Hu FL, Jiang B, Jiang HX, Lan CH, Li JN, Li Y, Li YQ, Liu J, Li YM, Lyu B, Lu YY, Miao YL, Nie YZ, Qian JM, Sheng JQ, Tang CW, Wang F, Wang HH, Wang JB, Wang JT, Wang JP, Wang XH, Wu KC, Xia XZ, Xie WF, Xie Y, Xu JM, Yang CQ, Yang GB, Yuan Y, Zeng ZR, Zhang BY, Zhang GY, Zhang GX, Zhang JZ, Zhang ZY, Zheng PY, Zhu Y, Zuo XL, Zhou LY, Lyu NH, Yang YS, Li ZS; National Clinical Research Center for Digestive Diseases (Shanghai), Gastrointestinal Early Cancer Prevention & Treatment Alliance of China (GECA), Helicobacter pylori Study Group of Chinese Society of Gastroenterology, and Chinese Alliance for Helicobacter pylori Study. Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition). Gut. 2022 Feb;71(2):238-253. doi: 10.1136/gutjnl-2021-325630. Epub 2021 Nov 26.
citation: Lv ZF, Wang FC, Zheng HL, Wang B, Xie Y, Zhou XJ, Lv NH. Meta-analysis: is combination of tetracycline and amoxicillin suitable for Helicobacter pylori infection? World J Gastroenterol. 2015 Feb 28;21(8):2522-33. doi: 10.3748/wjg.v21.i8.2522.
citation: Marko D, Calvet X, Ducons J, Guardiola J, Tito L, Bory F; GRESCA (Group for Eradication Studies from Catalonia and Aragon). Comparison of two management strategies for Helicobacter pylori treatment: clinical study and cost-effectiveness analysis. Helicobacter. 2005 Feb;10(1):22-32. doi: 10.1111/j.1523-5378.2005.00288.x.
citation: Calvet X, Montserrat A, Guell M, Vergara M, Gene E. Ranitidine-bismuth citrate, tetracycline and metronidazole followed by triple therapy as alternative strategy for Helicobacter pylori treatment: a pilot study. Eur J Gastroenterol Hepatol. 2004 Oct;16(10):987-90. doi: 10.1097/00042737-200410000-00006.
citation: Xie Y, Zhu Z, Wang J, Zhang L, Zhang Z, Lu H, Zeng Z, Chen S, Liu D, Lv N; the Chinese Study Group on Helicobacter pylori, Chinese Society of Gastroenterology. Ten-Day Quadruple Therapy Comprising Low-Dose Rabeprazole, Bismuth, Amoxicillin, and Tetracycline Is an Effective and Safe First-Line Treatment for Helicobacter pylori Infection in a Population with High Antibiotic Resistance: a Prospective, Multicenter, Randomized, Parallel-Controlled Clinical Trial in China. Antimicrob Agents Chemother. 2018 Aug 27;62(9):e00432-18. doi: 10.1128/AAC.00432-18. Print 2018 Sep.
citation: Zhang J, Han C, Lu WQ, Wang N, Wu SR, Wang YX, Ma JP, Wang JH, Hao C, Yuan DH, Liu N, Shi YQ. A randomized, multicenter and noninferiority study of amoxicillin plus berberine vs tetracycline plus furazolidone in quadruple therapy for Helicobacter pylori rescue treatment. J Dig Dis. 2020 May;21(5):256-263. doi: 10.1111/1751-2980.12870. Epub 2020 Jun 9.