Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication: Clinical, pharmacogenetic, and microbiome perspectives

Table 1 Key multicenter vonoprazan-based trials

Ref.	Region	Center (s)	n	Regimens	Duration	Eradication rate (ITT/PP)	AEs	Notes
Chey et al[29], 2022	United States/Europe	Multiple	1046	VPZ 20 mg BID + AMO 1 g TID (dual); VPZ + AMO + CLA 500 mg BID (triple); lansoprazole triple	14 days	Dual: 77%/79%; triple: 81%/85%	45%-51%	First large Western RCT; dual superior to PPI triple in CLA-resistant strains (70% vs 32%)
Qian et al[33], 2023	China	1	375	VHA: VPZ + AMO 750 mg QID; VA: VPZ + AMO 1 g BID; BQT (esomeprazole + AMO + CLA + bismuth)	10 days	VHA: 91%/93%; VA: 82%/85%; BQT: 88%/91%	VHA: 8%; VA: 9%; BQT: 20%	First head-to-head comparison; VHA noninferior to BQT with fewer AEs
Yan et al[31], 2024	China	3	314	VPZ + AMO 1 g TID (dual) vs BQT (esomeprazole + AMO + CLA + bismuth)	10 days vs 14 days	Dual: 86%/91%; BQT: 89%/91%	Dual: 26%; BQT: 53%	10-day dual noninferior to 14-day BQT; significantly lower AE rate
Cheung et al[34], 2024	China	1	298	VA (VPZ + AMO); VAC (VPZ + AMO + CLA); BQT (bismuth + esomeprazole + tetracycline + metronidazole)	14 days	VA: 96%/97%; VAC: 96%/97%; BQT: 92%/97%	VA: 39%; VAC: 56%; BQT: 71%	High efficacy in high CLA resistance area; VA best safety
Wu et al[14], 2025	China (Sichuan)	17	1717	VPZ 20 mg BID + AMO 0.5-1.0 g TID/QID	14 days	92%-97%/97%	5%-7%	Low-dose QID most tolerable; high compliance
Han et al[28], 2025	China	19	524	VACa (14-day): VPZ + AMO + CLA; VACb (10-day): VPZ + AMO + CLA; EBAC: Esomeprazole + bismuth + AMO + CLA	10-14 days	VACa: 88%/94%; VACb: 83%/91%; EBAC: 73%/81%	30%-37%	VPZ triple noninferior to bismuth quadruple
Song et al[50], 2025	China	Multiple	418	VPZ 20 mg BID + AMO 1 g TID	10 days vs 14 days	10-day: 83%/89%; 14-day: 88%/95%	NR	10-day not noninferior to 14-day; 24-hour pH > 6 for > 75% time
Tao et al[49], 2025	China	Multiple	500	VPZ 20 mg BID + AMO 750 mg QID/1 g TID	7-10 days	7-day: 82%-84%/86%-88%; 10-day: 90%-91%/93%-94%	10%-14%	7-day regimens < 90%; 10-day TID effective
Peng et al[48], 2025	China	13	900	VPZ 20 mg BID + AMO 0.5 g TID/1 g BID/1 g TID	14 days	LVA: 87%/87%; MVA: 92%/92%; HVA: 93%/93%	Similar	≥ 2 g/day AMO noninferior to 3 g/day
Hu et al[66], 2025	China	12	504	VPZ 20 mg BID + AMO 1 g BID (LVA) vs 1 g TID (HVA)	14 days	LVA: 85%/89%; HVA: 87%/92%	12%-17%	LVA noninferior; no lasting gut resistome effect
Zhang et al[30], 2025	China	1	250	VPZ 20 mg BID + AMO 1 g TID	14 days	92%/96%	11%	Noninferior to BQT; reduced antibiotic exposure
Zhang et al[54], 2025	China	4	688	VPZ 20 mg BID + AMO 1 g TID	14 days	74%/82%	13%	Rescue; noninferior to tetracycline-furazolidone quadruple
Gao et al[38], 2025	China	1	120	VPZ 20 mg BID + minocycline 100 mg BID (VM)	14 days	88%/92%	17%	Alternative for AMO resistance/penicillin allergy
Park et al[37], 2025	Korea	Multiple	102	VPZ + AMO + CLA vs tegoprazan 50/100 mg	10 days	VPZ: 85%/88%; tegoprazan 100: 79%/87%	Similar	Tegoprazan 100 mg comparable to VPZ; 50 mg insufficient
Geeratragool et al[41], 2025	Thailand	1	20	VPZ + AMO + sitafloxacin	7 days	70%/68%	15%	Fourth-line salvage; small sample; high genotypic resistance

Regimens include dual therapy (vonoprazan + amoxicillin) or triple therapy (vonoprazan + amoxicillin + clarithromycin or other). Data represent first-line or rescue treatment as indicated. Efficacy may vary by population, antibiotic resistance, and dosing schedule. Table consolidates multicenter randomized controlled trials and key comparative studies to highlight clinical evidence and relevant controversies. ITT: Intention-to-treat; PP: Per-protocol; AE: Adverse event; VPZ: Vonoprazan; AMO: Amoxicillin; BID: Twice a day; TID: Three times a day; CLA: Clarithromycin; VHA: Vonoprazan + amoxicillin high-dose; QID: Four times a day; VA: Vonoprazan + amoxicillin; BQT: Bismuth quadruple therapy; VAC: Vonoprazan + amoxicillin + clarithromycin; LVA/MVA/HVA: Low/medium/high-dose vonoprazan + amoxicillin; RCT: Randomized controlled trial; PPI: Proton pump inhibitor; NR: Not reported.

Table 2 Key factors affecting vonoprazan-amoxicillin dual therapy efficacy

Factor1	Sub-items/examples	Potential impact on vonoprazan-amoxicillin efficacy	Ref.
Population/geographic differences	Region, age, sex, dietary habits, healthcare access	Variation in eradication rates across countries, age groups, and healthcare systems	[6,21,46,58]
Host pharmacogenetics	CYP2C19/CYP3A4/CYP3A5 polymorphisms, age-related metabolism	Altered acid suppression, drug pharmacokinetics, variability in eradication success	[10,11,59,60,70]
Gut microbiome impact	Microbial diversity, SCFAs, dysbiosis, probiotic adjuncts	Short- and long-term ecological changes, potential resistome alteration	[23-25,36,56,61]
Antimicrobial resistance	Amoxicillin low but rising clarithromycin/metronidazole resistance; special populations (penicillin allergy, immunocompromised)	Treatment failure, need for alternative regimens, risk of resistance development	[9,26,30,38,40,43,54,55,60,61]
Treatment strategy optimization	Dose, duration, timing relative to meals	Suboptimal dose/duration reduces efficacy; careful selection required for 10-day vs 14-day regimens	[48,49,51,52,63,65-67]

¹Factors include population/geographic differences, host pharmacogenetics, microbiome impact, antimicrobial resistance, and treatment strategy optimization. The table summarizes sub-items, their potential impact on eradication success, and key references supporting each factor.

SCFA: Short-chain fatty acid.