Vonoprazan vs Proton Pump Inhibitor With Vitamin D or Probiotics Based Triple Therapy for Eradication of Helicobacter Pylori Infection

Summary

Helicobacter pylori is a Gram-negative, spiral-shaped bacterium that infects up to 50% of the world's population, residing in the gastric mucosa and using the mucus layer for protection from the stomach's high acidity. Its clinical significance is profound: it is classified as a Group 1 carcinogen by the World Health Organization and is a primary cause of chronic gastritis, peptic ulcers, gastric lymphoma, and gastric carcinoma. The current first-line treatment, a PPI-based triple therapy (PPI + clarithromycin + amoxicillin), is experiencing a decline in efficacy (cure rates of 50-70%) due to widespread antibiotic resistance and compliance issues. To overcome this, newer agents like Vonoprazan Fumarate, a Potassium-Competitive Acid Blocker (P-CAB), are being adopted. Vonoprazan works by reversibly inhibiting the H+, K+ ATPase pump achieving stronger and longer-lasting acid suppression than PPIs because it does not require acid activation and is more stable in an acidic environment. In addition to pharmacological treatment, adjunctive therapies show promise. Vitamin D, acting through Vitamin D Receptor (VDR), assists in eradication by upregulating antimicrobial proteins like beta-defensin and cathelicidin, and its metabolite can cause bacterial cell lysis. Probiotics (primarily Lactobacillus and Bifidobacterium strains) enhance eradication rates by restricting bacterial growth, inhibiting adhesion, and exerting an anti-inflammatory effect through decreased interleukin-8 production. Finally, helicobacter pylori infection is marked by significant inflammation and oxidative stress. The bacterial protein TIP alpha induces high levels of the pro-inflammatory cytokine TNF alpha. Furthermore, the infection increases free radical production, leading to oxidative stress reflected by high levels of malondialdehyde. Systemic inflammation is also evident as helicobacter pylori infection is associated with significantly elevated serum C-reactive protein levels, which decrease upon successful eradication. Aim of the work: This study aims at evaluating the safety and efficacy of Vonoprazan vs Proton Pump Inhibitor with Vitamin D or Probiotics Based Triple Therapy for Eradication of Helicobacter Pylori Infection.

Timeline

Start

2026-02-15

Primary completion

2026-12-20

Completion

2026-12-20

Publications

• Background Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J. 2005 Jul;19(9):1067-77. doi: 10.1096/fj.04-3284com.
• Background Wanibuchi K, Hosoda K, Ihara M, Tajiri K, Sakai Y, Masui H, Takahashi T, Hirai Y, Shimomura H. Indene Compounds Synthetically Derived from Vitamin D Have Selective Antibacterial Action on Helicobacter pylori. Lipids. 2018 Apr;53(4):393-401. doi: 10.1002/lipd.12043. Epub 2018 May 16.
• Background Murakami K, Sakurai Y, Shiino M, Funao N, Nishimura A, Asaka M. 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 Sep;65(9):1439-46. doi: 10.1136/gutjnl-2015-311304. Epub 2016 Mar 2.
• Background Hori Y, Imanishi A, Matsukawa J, Tsukimi Y, Nishida H, Arikawa Y, Hirase K, Kajino M, Inatomi N. 1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438), a novel and potent potassium-competitive acid blocker for the treatment of acid-related diseases. J Pharmacol Exp Ther. 2010 Oct;335(1):231-8. doi: 10.1124/jpet.110.170274. Epub 2010 Jul 12.
• Background Iannone A, Giorgio F, Russo F, Riezzo G, Girardi B, Pricci M, Palmer SC, Barone M, Principi M, Strippoli GF, Di Leo A, Ierardi E. New fecal test for non-invasive Helicobacter pylori detection: A diagnostic accuracy study. World J Gastroenterol. 2018 Jul 21;24(27):3021-3029. doi: 10.3748/wjg.v24.i27.3021.
• Background Schreiber S, Konradt M, Groll C, Scheid P, Hanauer G, Werling HO, Josenhans C, Suerbaum S. The spatial orientation of Helicobacter pylori in the gastric mucus. Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):5024-9. doi: 10.1073/pnas.0308386101. Epub 2004 Mar 25.
• Background Ceylan A, Kirimi E, Tuncer O, Turkdogan K, Ariyuca S, Ceylan N. Prevalence of Helicobacter pylori in children and their family members in a district in Turkey. J Health Popul Nutr. 2007 Dec;25(4):422-7.

Drugs

Indications