Vonoprazan-tetracycline: A promising rescue strategy for H. pylori
Two-drug regimen clears infection with fewer side effects after prior failure.
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02/13/2026
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by Doug Brunk
A 14-day regimen of vonoprazan plus tetracycline achieved eradication rates noninferior to bismuth quadruple therapy while significantly reducing adverse events in patients with prior treatment failure for Helicobacter pylori, according to a randomized controlled trial published in Gastroenterology.
A team of researchers in China conducted a prospective, open-label, noninferiority trial at Peking University First Hospital in Beijing. They enrolled 350 adults with confirmed H. pylori infection who had failed at least one previous treatment. Participants were randomly assigned in equal numbers to receive either vonoprazan–tetracycline dual therapy (VT) or bismuth quadruple therapy (BQT) for 14 days.
The VT regimen consisted of vonoprazan 20 mg twice daily and tetracycline 500 mg three times daily. BQT included lansoprazole 30 mg twice daily, colloidal bismuth 150 mg three times daily, tetracycline 500 mg three times daily and metronidazole 400 mg three times daily. The primary outcome of interest was noninferiority in eradication rates between the two groups.
In the modified intention-to-treat analysis, eradication rates were 90.6% (154 of 170) in the VT group and 89.3% (151 of 169) in the BQT group. The between-group difference was 1.2 percentage points (P = .0003 for noninferiority), which met the prespecified criterion.
Results were consistent across analytic populations. In the intention-to-treat analysis, eradication rates were 88.0% (154 of 175) with VT and 86.3% (151 of 175) with BQT (difference, 1.7 percentage points; P = .0005 for noninferiority). In the per-protocol analysis, rates were 91.1% (153 of 168) and 92.2% (141 of 153), respectively (difference, –1.1 percentage points; P = .002 for noninferiority). No statistically significant differences in eradication were observed between groups in any population (P = .75, .84 and .88, respectively).
Subgroup analysis by penicillin allergy showed similar outcomes. In the VT group, modified intention-to-treat eradication was 91.8% (101 of 110) in patients without penicillin allergy and 88.3% (53 of 60) in those with penicillin allergy. Corresponding rates in the BQT group were 89.4% (101 of 113) and 89.3% (50 of 56). Differences did not reach statistical significance.
In other findings, approximately 70% of study participants had failed at least one prior amoxicillin-containing regimen. In the VT group, 41% had failed two or more such regimens; in the BQT group, 35% had done so.
Safety outcomes favored the dual regimen. Treatment-emergent adverse events occurred in 10.9% (19 of 175) of patients receiving VT compared with 45.7% (80 of 175) receiving BQT (P < .001). Differences were significant for mild and severe adverse events, though not for moderate events. No patients in the VT group discontinued therapy because of adverse events, compared with 8.6% (15 of 175) in the BQT group (P < .001).
Adherence, defined as taking at least 80% of prescribed doses, was higher with VT (96.0% vs 87.4%; P = .01). Eleven patients were lost to follow-up and counted as treatment failures in the intention-to-treat analysis. Among those who discontinued prematurely, 2 patients in the VT group and 16 in the BQT group took fewer than 80% of prescribed medication; 15 discontinuations in the BQT arm were attributed to adverse events.
The trial was powered assuming an 88% eradication rate for BQT as rescue therapy, requiring 166 patients per group; enrollment was increased to 175 per arm to account for anticipated dropout.
The authors noted limitations of the study, including its single-center design and the fact that VT dual therapy as a rescue regimen has not yet been evaluated outside of China.
“In this randomized controlled trial conducted in [a] Chinese population, vonoprazan–tetracycline dual therapy was shown to be an effective and well-tolerated rescue regimen for Helicobacter pylori infection,” the authors concluded. “Its eradication rate was comparable to that of traditional tetracycline-metronidazole-based bismuth quadruple therapy, while it was associated with fewer adverse events and better adherence. By omitting bismuth and one additional antibiotic without compromising efficacy, this simplified regimen offers a practical, optimized alternative for rescue treatment, particularly for patients with penicillin allergy or with prior failure of amoxicillin-containing regimens.”
The study received support from National High Level Hospital Clinical Research Funding, Natural Science Foundation of Beijing Municipality, and National High Level Hospital Clinical Research Funding. The authors reported having no relevant disclosures.
Summary content
7 Key Takeaways
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The guidelines emphasize four-hour gastric emptying studies over two-hour testing. How do you see this affecting diagnostic workflows in practice?
Dr. Staller: Moving to a four-hour solid-meal scintigraphy will actually simplify decision-making. The two-hour reads miss a meaningful proportion of delayed emptying; standardizing on four hours reduces false negatives and the “maybe gastroparesis” purgatory that leads to repeat testing. Practically, it means closer coordination with nuclear medicine (longer slots, consistent standardized meal), updating order sets to default to a four-hour protocol, and educating front-line teams so patients arrive appropriately prepped. The payoff is fewer equivocal studies and more confident treatment plans.
Metoclopramide and erythromycin are the only agents conditionally recommended for initial therapy. How does this align with what is being currently prescribed?
Dr. Staller: This largely mirrors real-world practice. Metoclopramide remains the only FDA-approved prokinetic for gastroparesis, and short “pulsed” erythromycin courses are familiar to many of us—recognizing tachyphylaxis limits durability. Our recommendation is “conditional” because the underlying evidence is modest and patient responses are heterogeneous, but it formalizes what many clinicians already do: start with metoclopramide (lowest effective dose, limited duration, counsel on neurologic adverse effects) and reserve erythromycin for targeted use (exacerbations, bridging).
Several agents, including domperidone and prucalopride, received recommendations against first-line use. How will that influence discussions with patients who ask about these therapies?
Dr. Staller: Two points I share with patients: evidence and access/safety. For domperidone, the data quality is mixed, and US access is through an FDA IND mechanism; you’re committing patients to EKG monitoring and a non-trivial administrative lift. For prucalopride, the gastroparesis-specific evidence isn’t strong enough yet to justify first-line use. So, our stance is not “never,” it’s just “not first.” If someone fails or cannot tolerate initial therapy, we can revisit these options through shared decision-making, setting expectations about benefit, monitoring, and off-label use. The guideline language helps clinicians have a transparent, evidence-based conversation at the first visit.
The guidelines suggest reserving procedures like G-POEM and gastric electrical stimulation for refractory cases. In your practice, how do you decide when a patient is “refractory” to medical therapy?
Dr. Staller: I define “refractory” with three anchors.
1. Adequate trials of foundational care: dietary optimization and glycemic control; an antiemetic; and at least one prokinetic at appropriate dose/duration (with intolerance documented if stopped early).
2. Persistent, function-limiting symptoms: ongoing nausea/vomiting, weight loss, dehydration, ER visits/hospitalizations, or malnutrition despite the above—ideally tracked with a validated instrument (e.g., GCSI) plus nutritional metrics.
3. Objective correlation: delayed emptying on a standardized 4-hour solid-meal study that aligns with the clinical picture (and medications that slow emptying addressed).
At that point, referral to a center with procedural expertise for G-POEM or consideration of gastric electrical stimulation becomes appropriate, with multidisciplinary evaluation (GI, nutrition, psychology, and, when needed, surgery).
What role do you see dietary modification and glycemic control playing alongside pharmacologic therapy in light of these recommendations?
Dr. Staller: They’re the bedrock. A small-particle, lower-fat, calorie-dense diet—often leaning on nutrient-rich liquids—can meaningfully reduce symptom burden. Partnering with dietitians early pays dividends. For diabetes, tighter glycemic control can improve gastric emptying and symptoms; I explicitly review medications that can slow emptying (e.g., opioids; consider timing/necessity of GLP-1 receptor agonists) and encourage continuous glucose monitor-informed adjustments. Pharmacotherapy sits on top of those pillars; without them, medications will likely underperform.
The guideline notes “considerable unmet need” in gastroparesis treatment. Where do you think future therapies or research are most urgently needed?
Dr. Staller: I see three major areas.
1. Truly durable prokinetics: agents that improve emptying and symptoms over months, with better safety than legacy options (e.g., next-gen motilin/ghrelin agonists, better-studied 5-HT4 strategies).
2. Endotyping and biomarkers: we need to stop treating all gastroparesis as one disease. Clinical, physiologic, and microbiome/omic signatures that predict who benefits from which therapy (drug vs G-POEM vs GES) would transform care.
3. Patient-centered trials: larger, longer RCTs that prioritize validated symptom and quality-of-life outcomes, include nutritional endpoints, and reflect real-world medication confounders.
Our guideline intentionally highlights these gaps to hopefully catalyze better trials and smarter referral pathways.
Dr. Staller is with the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston.