Efficacy and safety of Qingwei Zhitong pellets (清胃止痛微丸)-containing quadruple therapy for Helicobacter pylori eradication: a prospective, single-center, randomized trial

doi:10.19852/j.cnki.jtcm.2025.02.021

Abstract

Abstract:

OBJECTIVE: To evaluate the efficacy and safety of 14-day Qingwei Zhitong pellets (清胃止痛微丸, QZ)-containing quadruple therapy (QZQT) compared to bismuth-containing quadruple therapy (BQT) in treatment-naive patients with Helicobacter pylori (H. pylori) infection.

METHODS: This single-center, randomized controlled clinical trial enrolled 333 patients, who were divided into either the QZQT group (QZ pellets, 3.2 g, three times daily; rabeprazole, 10 mg, twice daily; amoxicillin 1000 mg, twice daily; clarithromycin, 500 mg, twice daily) or the BQT group (bismuth potassium citrate, 1000 mg, three times daily; rabeprazole, 10 mg, twice daily; amoxicillin, 1000 mg, twice daily; clarithromycin, 500 mg, twice daily) for 14 d. The 13C-urea breath test assessed eradication success at least four weeks after treatment. The primary outcome focused on the eradication rate, with secondary outcomes including safety and patient compliance.

RESULTS: From August 2022 to June 2023, 342 subjects were screened, and 333 were randomized. The QZQT and BQT groups showed eradication rates of 68.9% and 67.8% (P = 0.838) by intention-to-treat (ITT) analysis, respectively, and 71.1% and 68.3% (P = 0.612) by per-protocol (PP) analysis, respectively. QZQT was non-inferior to BQT in both ITT and PP analyses. QZQT was associated with fewer side effects (57.8% of patients) than BQT (90.4%) (P < 0.001).

CONCLUSION: The 14 d QZQT treatment demonstrates equal efficacy in eradicating H. pylori infection and improved patient compliance and safety compared to BQT. These results provide evidence supporting 14-day QZQT as an acceptable treatment for H. pyloriinfection.

Key words: Helicobacter pylori, bismuth, randomized controlled trial, quadruple therapy, eradication, Qingwei Zhitong pellets

CHENG Jianping, FAN Chanjuan, ZHAI Lili, WANG Hui, XIE Dongling, CAI Yong, LI Zhen, HUANG Kun, BAI Qixuan. Efficacy and safety of Qingwei Zhitong pellets (清胃止痛微丸)-containing quadruple therapy for Helicobacter pylori eradication: a prospective, single-center, randomized trial[J]. Journal of Traditional Chinese Medicine, 2025, 45(2): 430-436.

Figures/Tables 3

References 41.

1.	Suzuki S, Gotoda T, Kusano C, et al. Seven-day vonoprazan and low-dose amoxicillin dual therapy as first-line Helicobacter pylori treatment: a multicentre randomised trial in Japan. Gut 2020; 69: 1019-26. DOI PMID
2.	Codolo G, Toffoletto M, Chemello F, et al. Helicobacter pylori dampens HLA-Ⅱ expression on macrophages via the up-regulation of miRNAs targeting CIITA. Front Immunol 2019; 10: 2923. DOI PMID
3.	Gunawardhana N, Jang S, Choi YH, et al. Helicobacter pylori-induced HB-EGF upregulates gastrin expression via the EGF receptor, C-Raf, Mek1, and Erk2 in the MAPK pathway. Front Cell Infect Microbiol 2017; 7: 541.
4.	Sun L, Talarico S, Yao L, et al. Droplet digital PCR-based detection of clarithromycin resistance in Helicobacter pylori isolates reveals frequent heteroresistance. J Clin Microbiol 2018; 56: 274.
5.	Ye H, Shi ZM, Chen Y, et al. Innovative perspectives of integrated Chinese medicine on H. pylori. Chin J Integr Med 2018; 24: 873-80.
6.	Ye H, Liu Y, Li N, et al. Anti-Helicobacter pylori activities of Chenopodium ambrosioides L. in vitro and in vivo. World J Gastroenterol 2015; 21: 4178-83.
7.	Wu JY, Liou JM, Graham DY. Evidence-based recommendations for successful Helicobacter pylori treatment. Expert Rev Gastroenterol Hepatol 2014; 8: 21-8.
8.	Song Z, Li B, Zhang Y, et al. Outer membrane vesicles of Helicobacter pylori 7.13 as adjuvants promote protective efficacy against Helicobacter pylori infection. Front Microbiol 2020; 11: 1340.
9.	Zhao M, Jiang Y, Chen Z, et al. Traditional Chinese Medicine for Helicobacter pylori infection: a protocol for a systematic review and meta-analysis. Medicine (Baltimore) 2021; 100: e24282.
10.	Lin J, Huang WW. A systematic review of treating Helicobacter pylori infection with traditional Chinese medicine. World J Gastroenterol 2009; 15: 4715-19.
11.	He LZ, Zhang Q, Wang SC. Clinical study on treatment of gastric ulcer with Qingwei Zhitong pill. Zhongguo Zhong Xi Yi Jie He Za Zhi 2001; 21: 422-3.
12.	Paavola M, Kanto K, Ranstam J, et al. Subacromial decompression versus diagnostic arthroscopy for shoulder impingement: a 5-year follow-up of a randomised, placebo surgery controlled clinical trial. Br J Sports Med 2021; 55: 99-107.
13.	Ren C, Mai ZJ, Jin Y, et al. Anti-PD-1 antibody SHR-1210 plus apatinib for metastatic colorectal cancer: a prospective, single-arm, open-label, phase Ⅱ trial. Am J Cancer Res 2020; 10: 2946-54.
14.	Bang CS, Lim H, Jeong HM, et al. Amoxicillin or tetracycline in bismuth-containing quadruple therapy as first-line treatment for Helicobacter pylori infection. Gut Microbes 2020; 11: 1314-23.
15.	Yang JC, Lin CJ, Wang HL, et al. High-dose dual therapy is superior to standard first-line or rescue therapy for Helicobacter pylori infection. Clin Gastroenterol Hepatol 2015; 13: 895-905.
16.	Zhou L, Lu H, Song Z, et al. 2022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment. Chin Med J (Engl) 2022; 135: 2899-2910.
17.	Murakami K, Sakurai Y, Shiino M, et al. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase Ⅲ, randomised, double-blind study. Gut 2016; 65: 1439-46.
18.	Hsu PI, Lin PC, Graham DY. Hybrid therapy for Helicobacter pylori infection: a systemic review and Meta-analysis. World J Gastroenterol 2015; 21: 12954-62.
19.	Hwang JJ, Lee DH, Lee AR, et al. Fourteen- vs seven-day bismuth-based quadruple therapy for second-line Helicobacter pylori eradication. World J Gastroenterol 2015; 21: 8132-39.
20.	Chey WD, Wong BCY, Gastroenterology PPCotACo. American college of gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol 2007; 102: 1808-25.
21.	Malfertheiner P, Megraud F, O'Morain CA, et al. Management of Helicobacter pylori infection — the Maastricht Ⅳ / Florence consensus report. Gut 2012; 61: 646-64.
22.	Wang L, Lin Z, Chen S, et al. Ten-day bismuth-containing quadruple therapy is effective as first-line therapy for Helicobacter pylori-related chronic gastritis: a prospective randomized study in China. Clin Microbiol Infect 2017; 23: 391-5.
23.	Huang Y, Wang QL, Cheng DD, et al. Adhesion and invasion of gastric mucosa epithelial cells by Helicobacter pylori. Front Cell Infect Microbiol 2016; 6: 159.
24.	Hu Q, Peng Z, Li L, et al. The efficacy of berberine-containing quadruple therapy on Helicobacter Pylori eradication in China: a systematic review and Meta-analysis of randomized clinical trials. Front Pharmacol 2019; 10: 1694.
25.	Nagaraja V, Eslick GD. Evidence-based assessment of proton-pump inhibitors in Helicobacter pylori eradication: a systematic review. World J Gastroenterol 2014; 20: 1427-36.
26.	Jing JJ, Liu HY, Hao JK, et al. Gastric cancer incidence and mortality in Zhuanghe, China, between 2005 and 2010. World J Gastroenterol 2012; 18: 1262-69.
27.	Jiao Y, Yang H, Qian J, et al. miR-3664-5P suppresses the proliferation and metastasis of gastric cancer by attenuating the NF-κB signaling pathway through targeting MTDH. Int J Oncol 2019; 54: 845-58.
28.	Yen CH, Chiu HF, Huang SY, et al. Beneficial effect of Burdock complex on asymptomatic Helicobacter pylori-infected subjects: a randomized, double-blind placebo-controlled clinical trial. Helicobacter 2018; 23: e12469.
29.	Hojo M, Asaoka D, Takeda T, et al. Randomized controlled study on the effects of triple therapy including vonoprazan or rabeprazole for the second-line treatment of Helicobacter pylori infection. Therap Adv Gastroenterol 2020; 13: 1756284820966247.
30.	Li C, Huang P, Wong K, et al. Coptisine-induced inhibition of Helicobacter pylori: elucidation of specific mechanisms by probing urease active site and its maturation process. J Enzyme Inhib Med Chem 2018; 33: 1362-75.
31.	Li Q, Qu X, Pang X, et al. Berberine protects mice against dextran sulfate sodium-induced colitis by activating mTORC 1 pathway. Front Pharmacol 2019; 10: 786.
32.	Tan L, Li C, Chen H, et al. Epiberberine, a natural protoberberine alkaloid, inhibits urease of Helicobacter pylori and jack bean: susceptibility and mechanism. Eur J Pharm Sci 2017; 110: 77-86.
33.	Lin YH, Lin JH, Chou SC, et al. Berberine-loaded targeted nanoparticles as specific Helicobacter pylori eradication therapy: in vitro and in vivo study. Nanomedicine (Lond) 2015; 10: 57-71.
34.	Chang CH, Huang WY, Lai CH, et al. Development of novel nanoparticles shelled with heparin for berberine delivery to treat Helicobacter pylori. Acta Biomater 2011; 7: 593-603.
35.	Zhang D, Ke L, Ni Z, et al. Berberine containing quadruple therapy for initial Helicobacter pylori eradication: an open-label randomized phase IV trial. Medicine (Baltimore) 2017; 96: e7697.
36.	Liang CM, Tai WC, Hsu PI, et al. Trend of changes in antibiotic resistance in Helicobacter pylori from 2013 to 2019:a multicentre report from Taiwan. Therap Adv Gastroenterol 2020; 13: 1756284820976990.
37.	Zhang YX, Zhou LY, Song ZQ, et al. Primary antibiotic resistance of Helicobacter pylori strains isolated from patients with dyspeptic symptoms in Beijing: a prospective serial study. World J Gastroenterol 2015; 21: 2786-92.
38.	Li SY, Li J, Dong XH, et al. The effect of previous eradication failure on antibiotic resistance of Helicobacter pylori: a retrospective study over 8 years in Beijing. Helicobacter 2021; 26: e12804.
39.	Megraud F, Coenen S, Versporten A, et al. Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut 2013; 62: 34-42.
40.	Savoldi A, Carrara E, Graham DY, et al. Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and Meta-analysis in World Health Organization regions. Gastroenterology 2018; 155: 1372-82.
41.	Emara MH, Mohamed SY, Abdel-Aziz HR. Lactobacillus reuteri in management of Helicobacter pylori infection in dyspeptic patients: a double-blind placebo-controlled randomized clinical trial. Therap Adv Gastroenterol 2014; 7: 4-13 DOI PMID

Variables		QZQT group (n = 166)	BQT group (n = 167)	P value
Age [years, median (IQR)]		37.5 (30.0-53.0)	36.0 (29.0-46.0)	0.134
Sex [n (%)]	Male	76 (45.8)	77 (46.1)	0.953
	Female	90 (54.2)	90 (53.9)
BMI (kg/m²)		23.69±3.76	23.18±3.53	0.208
Alcohol drinking [n (%)]		17 (10.2)	16 (9.6)	0.840
Cigarette smoking [n (%)]		37 (22.3)	27 (16.2)	0.156
Disease duration [n (%)]	≤1 month	117 (70.5)	119 (71.3)	0.876
	>1 month	49 (29.5)	48 (28.7)
Marital status [n (%)]	Married	114 (68.7)	100 (59.9)	0.094
	Single or divorced or widowed	52 (31.3)	67 (40.1)
Clinical condition [n (%)]	Epigastric pain	87 (52.4)	81 (48.5)	0.476
	Acid reflux	81 (48.8)	83 (49.7)	0.869
	Heartburn	62 (37.3)	69 (41.3)	0.459
	Epigastric distention	104 (62.7)	119 (71.3)	0.095
	Nausea	50 (30.1)	69 (41.3)	0.033
	Dry stool	50 (30.1)	36 (21.6)	0.074
	Dry mouth	82 (49.4)	82 (49.1)	0.957
	Bitter taste of mouth	56 (33.7)	56 (33.5)	0.969
	Oral malodour	87 (52.4)	86 (51.5)	0.868
	Irritability	58 (34.9)	50 (29.9)	0.330
	Diarrhea	56 (33.7)	50 (29.9)	0.457
	Constipation	70 (42.2)	58 (34.7)	0.476
Comorbidity	Diabetes	8 (4.8)	6 (3.6)	0.577
	Hypertension	15 (9.0)	22 (13.2)	0.230
Baseline GSRS [scores, median (IQR)]		7.00 (3.75-11.00)	7.00 (4.00-11.00)	0.419
DOB of ¹³C-UBT [median (IQR)]		13.65 (6.95-25.43)	16.10 (9.28-26.85)	0.306

Variables		QZQT group (n = 166)	BQT group (n = 167)	P value
Age [years, median (IQR)]		37.5 (30.0-53.0)	36.0 (29.0-46.0)	0.134
Sex [n (%)]	Male	76 (45.8)	77 (46.1)	0.953
	Female	90 (54.2)	90 (53.9)
BMI (kg/m²)		23.69±3.76	23.18±3.53	0.208
Alcohol drinking [n (%)]		17 (10.2)	16 (9.6)	0.840
Cigarette smoking [n (%)]		37 (22.3)	27 (16.2)	0.156
Disease duration [n (%)]	≤1 month	117 (70.5)	119 (71.3)	0.876
	>1 month	49 (29.5)	48 (28.7)
Marital status [n (%)]	Married	114 (68.7)	100 (59.9)	0.094
	Single or divorced or widowed	52 (31.3)	67 (40.1)
Clinical condition [n (%)]	Epigastric pain	87 (52.4)	81 (48.5)	0.476
	Acid reflux	81 (48.8)	83 (49.7)	0.869
	Heartburn	62 (37.3)	69 (41.3)	0.459
	Epigastric distention	104 (62.7)	119 (71.3)	0.095
	Nausea	50 (30.1)	69 (41.3)	0.033
	Dry stool	50 (30.1)	36 (21.6)	0.074
	Dry mouth	82 (49.4)	82 (49.1)	0.957
	Bitter taste of mouth	56 (33.7)	56 (33.5)	0.969
	Oral malodour	87 (52.4)	86 (51.5)	0.868
	Irritability	58 (34.9)	50 (29.9)	0.330
	Diarrhea	56 (33.7)	50 (29.9)	0.457
	Constipation	70 (42.2)	58 (34.7)	0.476
Comorbidity	Diabetes	8 (4.8)	6 (3.6)	0.577
	Hypertension	15 (9.0)	22 (13.2)	0.230
Baseline GSRS [scores, median (IQR)]		7.00 (3.75-11.00)	7.00 (4.00-11.00)	0.419
DOB of ¹³C-UBT [median (IQR)]		13.65 (6.95-25.43)	16.10 (9.28-26.85)	0.306

Variable		QZQT grou (n = 166)	BQT group (n = 167)	P value
Total patients		96 (57.8)	151 (90.4)	< 0.001
Adverse events	Dizziness	9 (5.4)	13 (7.8)	0.385
	Skin rash	6 (3.6)	10 (6.0)	0.311
	Black stools	46 (27.7)	140 (83.8)	< 0.001
	Diarrhea with black stools	4 (2.4)	29 (17.4)	< 0.001
	Diarrhea	15 (9.0)	30 (18.0)	0.017
	Bitter taste of mouth	40 (24.1)	92 (55.1)	< 0.001
	Nausea	9 (5.4)	16 (9.6)	0.150
	Abdominal pain	17 (10.2)	16 (9.6)	0.840
	Abdominal distension	18 (10.8)	11 (6.6)	0.168
	Constipation	13 (7.8)	15 (9.0)	0.705
	Dysgeusia (taste change)	4 (2.4)	10 (6.0)	0.104
Treatment compliance		161 (96.9)	161 (96.4)	0.612

Variable		QZQT grou (n = 166)	BQT group (n = 167)	P value
Total patients		96 (57.8)	151 (90.4)	< 0.001
Adverse events	Dizziness	9 (5.4)	13 (7.8)	0.385
	Skin rash	6 (3.6)	10 (6.0)	0.311
	Black stools	46 (27.7)	140 (83.8)	< 0.001
	Diarrhea with black stools	4 (2.4)	29 (17.4)	< 0.001
	Diarrhea	15 (9.0)	30 (18.0)	0.017
	Bitter taste of mouth	40 (24.1)	92 (55.1)	< 0.001
	Nausea	9 (5.4)	16 (9.6)	0.150
	Abdominal pain	17 (10.2)	16 (9.6)	0.840
	Abdominal distension	18 (10.8)	11 (6.6)	0.168
	Constipation	13 (7.8)	15 (9.0)	0.705
	Dysgeusia (taste change)	4 (2.4)	10 (6.0)	0.104
Treatment compliance		161 (96.9)	161 (96.4)	0.612

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