Clinical trial NCT06564246: Clinical Study Evaluating The Role of Vonoprazan Versus Pantoprazole in Patients With Gastroesophageal Reflux Disease
Official title: Clinical Study Evaluating The Role of Vonoprazan Versus Pantoprazole in Patients With Gastroesophageal Reflux Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Gastroesophageal Reflux Disease (GERD)
Keywords: Vonoprazan
Pantoprazole
Gastroesophageal Reflux Disease (GERD)
Gastrin serum level
E-Cadherin level
Lead sponsor: Tanta University
Sponsor class: OTHER
First posted: 2024-08-21
Enrollment: 44
Sex: ALL
Minimum age (years): 17
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: * Group 1 (control group): 22 patients who will receive Vonoprazan 20mg (Vonseca) and placebo of pantoloc daily for 8 weeks.
* Group 2: 22 patients who will receive Pantoprazole 40 mg (Pantoloc) and placebo of vonseca daily for 8 weeks.
Primary purpose: TREATMENT

Brief summary: This study aims to investigate the possible efficacy of vonoprazan versus Pantoprazole in patients with gastroesophageal reflux disease.

Detailed description: Gastroesophageal reflux disease (GERD) occurs when stomach acid repeatedly flows back into the esophagus with or without histological changes. However, the excessive reflux of gastric acid induces some complications, such as esophagitis, esophageal stenosis, cancer or Barrett's esophagus. GERD is classified into two categories: nonerosive reflux disease (NERD) and erosive esophagitis. NERD is characterized by the presence of the typical symptoms of GERD without visible erosive esophagitis on endoscopy. Erosive esophagitis is characterized by injury to the esophageal mucosa on endoscopy. The major symptoms of GERD include heartburn, acid regurgitation and decrease the patient's quality of life (QOL). Therefore, improvement in the QOL of these patients by supplying rapid relief of symptoms is the primary objective of treatment.

For decades, proton pump inhibitors (PPIs) have been the mainstay of treatment for erosive esophagitis. Long-term maintenance therapy with PPIs is also recommended to keep healing in patients with more severe erosive esophagitis, given that recurrence occurs in nearly 100% of such patients without therapy. Furthermore, PPIs are restricted in their time of dosing. PPIs are prodrugs that are converted to their active form in the acidic environment of the secretory canaliculus, which is also the sole location of active proton pumps in the parietal cell. Thus, PPIs only inhibit active proton pumps. Given their limited duration of action (half-life nearly 1-2 hours), PPI are taken 30 to 60 minutes before a meal so their presence in the secretory canaliculus coincides with the postprandial peak in active proton pumps.

An alternative therapy for patients who may not respond to PPIs and that does not have the requirement for dosing around meals might be of utility. Such a potential alternative therapy is a potassium competitive acid blocker (PCAB), a new class of antisecretory agent that supplies more potent inhibition of gastric acid than PPI.

PCAB exhibits a more rapid onset of action than PPIs and achieves a maximum acid inhibitory effect on the 1st day after treatment, while PPIs require 3-5 days. However, few studies have examined whether the rapid onset of vonoprazan contributes to the clinical effects on the typical GERD symptoms of heartburn and acid regurgitation.

The previously mentioned findings highlight the need for further studies to evaluate the role of vonoprazan in patients with gastroesophageal reflux disease.

Aim of the Work The aim of this study is to investigate the possible efficacy of vonoprazan versus Pantoprazole in patients with gastroesophageal reflux disease.

Eligibility criteria: Inclusion Criteria:

* Age 17-60 years.
* Both genders.
* Patients with a score ≥ 8 on the Gastroesophageal Reflux Disease Questionnaire (Gerd Q) are defined as having GERD and will enroll in this study and it will be done at baseline and after 8 weeks.

Exclusion Criteria:

* Subjects with history of gastrointestinal disease, gastroduodenal surgery, inflammatory bowel disease and Barrett's esophagus.
* Subjects with an earlier or current history of Zollinger-Ellison syndrome, or other gastric acid hypersecretion disorders (gastric or duodenal ulcer).
* Subjects with history of total/subtotal gastrectomy and esophageal achalasia.
* Subjects with Corona virus disease (COVID19).
* Subjects with major cardiological, respiratory, endocrine metabolic disease and neuro-psychological disease.
* Pregnancy or lactation.
* Subjects with total bilirubin level ≥ 1.2 mg/dl and ALT level \> 100 IU/l.
* Subjects with renal impairment (Crcl less than 30 ml/min).
* Patients receiving atazanavir sulphate, nelfinavir and rilpivirine hydrochloride due to potential drug interactions.

Primary outcomes:
measure: change in the measured biomarker
timeFrame: Before and after 2 months
Secondary outcomes:
measure: Change in gastroesophageal reflux disease symptoms (The Structured Assessment of Gastrointestinal Symptoms Questionnaire).
timeFrame: Before and after 2 months
Other outcomes:
Locations:
city: Giza
country: Egypt
facility: Theodore Billiharz Institute for Researchs
Study officials:
affiliation: Master degree student at faculty of pharmacy - Tanta university
name: Aya Hany Abdel Aziz
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kim YS, Kim TH, Choi CS, Shon YW, Kim SW, Seo GS, Nah YH, Choi MG, Choi SC. Effect of itopride, a new prokinetic, in patients with mild GERD: a pilot study. World J Gastroenterol. 2005 Jul 21;11(27):4210-4. doi: 10.3748/wjg.v11.i27.4210.
citation: Sakurai K, Suda H, Fujie S, Takeichi T, Okuda A, Murao T, Hasuda K, Hirano M, Ito K, Tsuruta K, Hattori M. Short-Term Symptomatic Relief in Gastroesophageal Reflux Disease: A Comparative Study of Esomeprazole and Vonoprazan. Dig Dis Sci. 2019 Mar;64(3):815-822. doi: 10.1007/s10620-018-5365-0. Epub 2018 Nov 10.
citation: Altomare A, Guarino MP, Cocca S, Emerenziani S, Cicala M. Gastroesophageal reflux disease: Update on inflammation and symptom perception. World J Gastroenterol. 2013 Oct 21;19(39):6523-8. doi: 10.3748/wjg.v19.i39.6523.
citation: Armstrong D. Endoscopic evaluation of gastro-esophageal reflux disease. Yale J Biol Med. 1999 Mar-Jun;72(2-3):93-100.
citation: Hongo M, Kinoshita Y, Miwa H, Ashida K. The demographic characteristics and health-related quality of life in a large cohort of reflux esophagitis patients in Japan with reference to the effect of lansoprazole: the REQUEST study. J Gastroenterol. 2008;43(12):920-7. doi: 10.1007/s00535-008-2257-7. Epub 2008 Dec 24.
citation: Pace F, Negrini C, Wiklund I, Rossi C, Savarino V; ITALIAN ONE INVESTIGATORS STUDY GROUP. Quality of life in acute and maintenance treatment of non-erosive and mild erosive gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2005 Aug 15;22(4):349-56. doi: 10.1111/j.1365-2036.2005.02558.x.
citation: Laine L, DeVault K, Katz P, Mitev S, Lowe J, Hunt B, Spechler S. Vonoprazan Versus Lansoprazole for Healing and Maintenance of Healing of Erosive Esophagitis: A Randomized Trial. Gastroenterology. 2023 Jan;164(1):61-71. doi: 10.1053/j.gastro.2022.09.041. Epub 2022 Oct 10.
citation: Shin JM, Kim N. Pharmacokinetics and pharmacodynamics of the proton pump inhibitors. J Neurogastroenterol Motil. 2013 Jan;19(1):25-35. doi: 10.5056/jnm.2013.19.1.25. Epub 2013 Jan 8.
citation: Abdel-Aziz Y, Metz DC, Howden CW. Review article: potassium-competitive acid blockers for the treatment of acid-related disorders. Aliment Pharmacol Ther. 2021 Apr;53(7):794-809. doi: 10.1111/apt.16295. Epub 2021 Feb 16.
citation: Laine L, Sharma P, Mulford DJ, Hunt B, Leifke E, Smith N, Howden CW. Pharmacodynamics and Pharmacokinetics of the Potassium-Competitive Acid Blocker Vonoprazan and the Proton Pump Inhibitor Lansoprazole in US Subjects. Am J Gastroenterol. 2022 Jul 1;117(7):1158-1161. doi: 10.14309/ajg.0000000000001735. Epub 2022 Mar 16.
citation: Koloski NA, Jones M, Hammer J, von Wulffen M, Shah A, Hoelz H, Kutyla M, Burger D, Martin N, Gurusamy SR, Talley NJ, Holtmann G. The Validity of a New Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS) for Evaluating Symptoms in the Clinical Setting. Dig Dis Sci. 2017 Aug;62(8):1913-1922. doi: 10.1007/s10620-017-4599-6. Epub 2017 May 27.