Comparing the Efficacy of Pantoprazole and Vonoprazan for Stress Ulcer Prophylaxis in Critically Patients Admitted to the ICU, a RCT study

Compare pantoprazole vs vonoprazan for stress bleeding prophylaxis in ICU.

Parallel two-arm RCT, blocks 4&6, 1:1 allocation, opaque numbered envelopes. Double-blinded (patients, staff, analyst blinded). Drugs identically packaged by pharmacy.

The intensive care unit of Imam Reza Hospital in Kermanshah. Patients are screened daily; after obtaining informed consent, randomization and drug administration by the nurse are performed. Daily monitoring for bleeding, hemodynamic changes, transfusion needs, and other outcomes is recorded by a trained researcher on pre‑designed checklists.

Age above 18 years; admission to the intensive care unit with anticipated stay beyond 48 hours; need for stress ulcer prophylaxis according to the American Society of Health‑System Pharmacists or the Society of Critical Care Medicine guidelines, defined as having at least one major risk factor including mechanical ventilation beyond 48 hours, or coagulopathy with an international normalized ratio above 1.5 or platelet count below fifty thousand per mm³, or having at least two minor risk factors including sepsis, shock, acute renal failure, liver failure, severe burns, trauma or severe central nervous system injury, or high‑dose corticosteroid use equivalent to more than 250 milligrams of hydrocortisone daily.

Pantoprazole: 40mg IV daily until discharge, full feeding, bleeding or 14d. Vonoprazan: 20mg oral via NG tube same duration.

Occurrence of clinically important gastrointestinal bleeding during intensive care unit stay; Occurrence of overt gastrointestinal bleeding without hemodynamic compromise; ventilator‑associated pneumonia; Clostridioides difficile infection; length of intensive care unit stay; 28‑day mortality.

Randomization Method: Block randomization with variable block sizes (4 and 6). Unit of Randomization: Individual (each patient is allocated separately). The random sequence is generated by R software. Allocation is performed using sequentially numbered, opaque, sealed envelopes. The envelope for each patient is opened only after confirming eligibility and obtaining consent.

Eligible patients will be allocated in a 1:1 ratio to either the vonoprazan or pantoprazole group after obtaining informed consent. The randomization sequence will be generated using R software with block randomization, employing variable block sizes of 4 and 6, by a biostatistician who will have no involvement in the study execution. Patient allocation will be performed using sequentially numbered, opaque, sealed envelopes (SNOSE). After verification of eligibility criteria and obtaining consent, the corresponding envelope will be opened by the responsible individual, and the patient will be assigned to one of the two groups. Outcome assessors and the statistical analyst will remain blinded to the intervention type until the completion of the study. Drug type, demographic and clinical data (e.g., APACHE II score at admission), and daily outcomes will be collected solely by a trained researcher/nurse who has no role in the treatment process. Data will be recorded daily at the patient's bedside in the ICU using paper case report forms.

Participant data file: individual participant data after removal of identifiers, including demographics, intervention group, primary and secondary outcomes, and confounders, shareable upon request by qualified researchers. Study protocol: full version including objectives, methods, inclusion and exclusion criteria, and randomization method. Statistical analysis plan: description of statistical methods, tests, and models used. Informed consent form: the text of the consent form provided to participants and signed by them, without including participants' identifying information. Clinical study report: final report of the study results. Analysis codes: R software codes used for data analysis. Data dictionary: complete definition of all variables and their coding.

Access to the data and documents begins 6 months after publication of the study results.

Available only to researchers affiliated with academic institutions.

The data and documents may be used only for research and academic purposes, including secondary analyses, reproduction of results, and meta‑analysis. Commercial use, transfer of data to third parties, and any attempt to identify participants are prohibited. Applicants must submit a written request including the study title, objectives, analysis methods, and list of researchers. The request is accepted after review and approval by the scientific and ethics committee of the study, and upon signing a confidentiality and data use agreement. Results must be reported to the study team after publication.

Applicants can submit their request via email to mjavad.alibakhshi@kums.ac.ir. If needed, correspondence is also possible through the postal address of the Vice Chancellery for Research and Technology, Medical Sciences Building Number 2, Shahid Beheshti Boulevard, Kermanshah, Iran. Responses are provided by the study principal investigator. The first priority for contact is email, followed by postal correspondence.

The applicant first submits a written request including the study title, objectives, analysis methods, and list of researchers. The request is reviewed within 7 working days and referred to the scientific and ethics committee of the study for approval. This stage takes about 14 to 21 working days. After approval, a confidentiality and data use agreement is sent to the applicant, and upon signing and returning it, the data or documents are delivered within 7 working days. Overall, the process takes about 4 to 6 weeks.