Comparison of Vonoprazan and Pantoprazole in Achieving Target Gastric pH for the Prevention of Stress Ulcers in the Intensive Care Unit: A Randomized Controlled Trial

To compare the efficacy and safety of Vonoprazan versus Pantoprazole in achieving target gastric pH for the prevention of stress ulcers in ICU patients.

A randomized, single-blind, active-controlled, single-center, parallel-group, Phase 3 clinical trial with a sample size of 40 patients. Randomization will be performed using block randomization with a 1:1 ratio.

This study will be conducted in the ICU of Kosar Hospital in Semnan. Eligible patients are randomly assigned to one of the two treatment groups (vonoprazan or pantoprazole) after informed consent. Drug intervention will continue until discharge from the ICU.

Inclusion criteria: Adult ICU patients requiring stress ulcer prophylaxis; Exclusion criteria: active GI bleeding, current PPI/H2RA use, contraindications, severe organ impairment, pregnancy/lactation, anticipated ICU stay < 72 hours.

Intervention group: Vonoprazan 20 mg orally or via NGT every 24 hours. Control group: Pantoprazole 40 mg IV every 24 hours.

Mean gastric fluid pH in the first 72 hours of intervention

Patients will be randomly allocated to the intervention (Vonoprazan) and control (Pantoprazole) groups in a 1:1 ratio using block randomization. The operational steps are as follows: 1. Sequence Generation: An independent researcher, uninvolved in sampling, will generate the random allocation sequence using the Sealed Envelope website (www.sealedenvelope.com) with a block size of 4. 2. Allocation Concealment: The generated codes will be placed inside sequentially numbered, opaque, and sealed envelopes. 3. Implementation: Upon the admission of an eligible patient to the ICU, the researcher will open the envelope in sequential order to determine and assign the patient’s treatment group.

This is a single-blind study in which only the data analyst is blinded to the allocated interventions. To ensure the data analyst remains unaware of the treatment groups, the collected data will be coded by another researcher (uninvolved in data analysis) before being handed over. The column containing the actual drug names will be removed, and the groups will be renamed using anonymous codes, such as “Group A” and “Group B”. The data analyst will perform all statistical analyses on these coded groups and will remain completely blinded to which code represents Vonoprazan or Pantoprazole until the final analysis is completed and the results are extracted.

Anonymized Individual Participant Data (IPD): All collected participant data after removal of identifying information (e.g., name, national ID, exact date of birth, etc.), including demographic information, physiological parameters (e.g., gastric pH at various time points), clinical outcomes (e.g., GI bleeding, VAP, CDI, length of stay, mortality), and other variables recorded in the Case Report Form (CRF). Study Protocol: The complete version of the study protocol, including details of methodology, inclusion/exclusion criteria, intervention procedures, outcomes, and data analysis methods. Statistical Analysis Plan: A detailed plan of the statistical analyses intended for examining study outcomes and hypotheses. Clinical Study Report: A comprehensive report of the study findings after completion and data analysis. Data Dictionary: A file containing precise definitions of all collected variables, their units of measurement, and coding methods.

Access Period Start: 6 months after the publication of the study results (journal article print). Access Duration: Data and documents will be available for 10 years from the start of the access period.

Researchers affiliated with accredited academic and scientific institutions, clinicians, and healthcare professionals who present a relevant research proposal and require the data for non-commercial research purposes.

Purpose: Analysis and examination of primary and secondary study outcomes. Conducting secondary and ancillary studies based on the available data. Validation of the current study's findings. Use in related research projects concerning stress ulcer prophylaxis and gastric acid management in ICU patients. Conditions: Submission of a written request detailing the research plan, objectives, methodology, and data analysis strategy. Completion of a Non-Disclosure Agreement (NDA) and Data Use Agreement. Approval of the research proposal by the Institutional Review Board (IRB) or Ethics Committee of the researcher's institution. Exclusive use for non-commercial research purposes; no redistribution of data to third parties without explicit permission. Proper citation of the original study in all reports and publications derived from this data.

Interested applicants may contact the study's research coordinator via email: Contact Person: Dr. Mohammad Memarian Title: Supervisor, Research Officer Email: aria2018@gmail.com paniz1re@gmail.com Mailing address: Semnan, Golestan Town, Amin Boulevard, Kowsar Hospital Postal Code: 3519899951

1. Request Submission: The applicant submits a written request along with their research proposal and completed forms (NDA, Data Use Agreement) via email or mail. 2. Request Review: The request is reviewed by the research lead and relevant committee. Upon approval of the research proposal and adherence to the terms, further steps are initiated. (Estimated Review Time: 2-4 weeks) 3. Notification of Decision: The applicant is informed of the decision (approval or rejection). 4. Data/Document Delivery: Upon approval, the data and documents will be securely delivered to the applicant (e.g., via an encrypted download link or secure cloud storage). (Estimated Delivery Time: 1-2 weeks post-approval)

This study was conducted with the aim of advancing scientific knowledge and improving patient care in intensive care units. We are eager to collaborate with other interested researchers to leverage this data for the advancement of scientific research.