Clinical Study Of A Vonoprazan-Based Rescue Therapy For The Treatment Of Helicobacter Pylori Infection

Background and AimsHelicobacter pylori（H.pylori）infection is a global public health problem which has become a worldwide public health burden.Data from extensive clinical studies show that H.pylori is not only a risk factor for chronic gastritis,peptic ulcer,gastric adenocarcinoma and other digestive diseases,but also for various extra-digestive diseases such as autoimmune diseases,and cardiovascular diseases.Eradication of H.pylori can effectively relieve the symptoms of gastritis and dyspepsia,prevent the recurrence of peptic ulcer,and also reduce the incidence of gastric cancer.Currently,several national and international consensuses recommend 14-day bismuth-containing quadruple therapy（BQTs）as the first-line treatment regimen for H.pylori infection.However,due to the complexity,high cost and adverse effects of the regimen,poor patient compliance,and the increase of drug-resistant bacteria due to the use of multiple antibiotics,there are still patients who have not successfully eradicated H.pylori after treatment with BQTs regimen.In addition,multiple eradication failures often increase the prevalence of multidrug-resistant H.pylori strains,making rescue treatment more difficult.Therefore,exploring safe and effective rescue therapy for H.pylori infection is an urgent therapeutic challenge for clinicians at present.Vonoprazan（VPZ）is the first clinically available potassium-competing acid blocker（P-CAB）in recent years and has a more rapid and sustained acid inhibition effect than conventional proton pump inhibitors（PPIs）.This provides an opportunity to improve the management of H.pylori eradication therapy,particularly by simplifying complex eradication regimens and possibly developing very effective therapies.In addition,probiotics have come to be widely used in clinical practice in recent years,and"treating bacteria with probiotics"is gradually becoming a new strategy for the treatment of H.pylori infection.Therefore,this exploratory study aims to evaluate the efficacy and safety of VPZ in combination with amoxicillin（VA-dual）with Saccharomyces boulardii（S.boulardii）supplements as a rescue therapy for H.pylori infection.In addition,factors that may affect the eradication rate of H.pylori will be further explored,and it is recommend that these novel points be incorporated in clinical practice to improve the eradication rate.Materials and MethodsA total of 68 patients with a history of at least one failed eradication treatment and attended the department of gastroenterology between January 2022 and August 2022were screened for eligibility.The H.pylori infection was confirmed by ¹³C urea breath test(¹³C-UBT),histological examination or rapid urease test.All were treated with VPZ（20 mg twice daily）,amoxicillin（750 mg three times daily）and S.boulardii（250mg twice daily）for 14 days（14d-VAS）.VPZ and S.boulardii were administered before breakfast and dinner,amoxicillin was administered after breakfast,lunch,and dinner.Within 3 days of the end of treatment,patients’adverse events were recorded and compliance was assessed.At 4-6 weeks after the end of treatment,all patients were underwent ¹³C‐UBT to assess H.pylori status.ResultsA total of 68 patients were enrolled.The times of previous eradication failures ranged from 1 to 3.The overall eradication rate of 14d-VAS using intention-to-treat（ITT）analysis and protocol（PP）analysis was 92.6%（63/68）and 92.3%（60/65）,respectively.The ITT eradication rates were 93.6%,93.3%and 83.3%（P=0.433）,and the PP eradication rates were 93.2%,93.3%and 83.3%（P=0.585）,respectively in patients who had failed one time,two times and three times previously.There was no statistical difference in eradication rate according to different previous failure times.Superior H.pylori eradication was related to non-anxiety patients（96.8%in non-anxiety patients vs.60.0%in anxiety patients,P=0.025）.A total of 10 patients（14.7%）had adverse events.Most adverse events were mild and disappeared without intervention.95.6%of patients（65/68）had good compliance.24 out of 68 patients（35.3%）received H.pylori culture and antimicrobial susceptibility testing.H.pylori was successfully isolated in 95.8%（23/24）of patients.The resistance rates for clarithromycin,metronidazole and levofloxacin were 91.3%（21/23）,100%（23/23）and60.0%（14/23）,respectively.There was no resistance to amoxicillin,tetracycline or furazolidone.In 60.9%（14/23）patients,H.pylori was resistant to clarithromycin,metronidazole and levofloxacin.The triple drug resistance rate（clarithromycin,metronidazole,and levofloxacin）was 56.3%（9/16）among patients with one time therapy failure and further increased to 71.4%（5/7）among patients who had failed two or more times previously.ConclusionsIn conclusion,this study demonstrated that the 14d-VAS regimen is a safe and effective rescue therapy for H.pylori infection,regardless of how many times patients have failed.Successful eradication is also associated with patients without anxiety disorders,which warrants further stratified analysis in the future to refine and optimize this rescue therapy.