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IRCT20260914071059N1 IRCT 2026-09-16 Yazd University of Medical Sciences Effect of Vitamin B12 and Folic Acid on Preventing Platelet Count Reduction in Patients Receiving Concomitant Meropenem and Linezolid Treatment Comparison of Combined Vitamin B12 and Folic Acid Supplementation with Placebo for the Prevention of Thrombocytopenia in Patients Receiving Concomitant Treatment with Meropenem and Linezolid: A Randomized Double-Blind Clinical Trial 2026-10-07 anticipated 36 Recruiting https://irct.ir/trial/93367 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Used, Assignment: Parallel, Purpose: Prevention, Randomization description: The individual participant will be the unit of randomization. After confirmation of eligibility and obtaining written informed consent, 36 participants will be allocated in a 1:1 ratio to either the intervention group with 18 participants or the placebo control group with 18 participants. Before the beginning of recruitment, the allocation sequence will be generated by the independent research pharmacist using permuted block randomization with a fixed block size of four and the Sealed Envelope web-based randomization tool available at https://www.sealedenvelope.com/simple-randomiser/v1/lists. No stratification will be used. Each allocation will be linked to a unique sequential code, and the independent pharmacist will prepare identically appearing, sequentially numbered intervention and placebo packages according to the randomization sequence. Each eligible participant will receive the next consecutively numbered package in the order of enrollment. The allocation list and the code key will be securely retained by the independent pharmacist and will not be accessible to recruiters, participants, clinical care providers, investigators, outcome assessors, or the data analyst until completion of the final analysis. This procedure will ensure allocation concealment, Blinding description: The random allocation sequence will be provided to an independent research pharmacist. The pharmacist will prepare, package, and code the intervention products, including vitamin B12 and folic acid, and the matching placebo so that they are identical in appearance, color, size, shape, and packaging. Participants, clinical care providers, principal investigators, outcome assessors and data collectors, and the data analyst will remain unaware of group allocation and the meaning of the codes. The allocation code will be kept exclusively by the independent research pharmacist and will be disclosed to the research team after completion of the final data analysis. No independent data safety and monitoring committee will be established for this study. 3 Thrombocytopenia associated with meropenem and linezolid treatment. Intervention 1: Intervention group: Participants will receive 1,000 micrograms of oral vitamin B12 once daily and 1 milligram of oral folic acid once daily for seven days, starting concurrently with meropenem and linezolid treatment. Standard treatment with meropenem and linezolid will be administered according to the treating physician's judgment and the hospital protocol. Intervention 2: Control group: Participants will receive matching oral placebo for seven days with the same number of dosage units, appearance, color, size, shape, packaging, and administration schedule as the active supplements. Standard treatment with meropenem and linezolid will be administered according to the treating physician's judgment and the hospital protocol. Yes - There is a plan to make this available What will be shared: Deidentified individual participant data underlying the published results will be shared, including demographic variables, baseline characteristics, intervention allocation, platelet counts, occurrence and severity of thrombocytopenia, antibiotic discontinuation, length of hospital stay, and adverse events. The study protocol, statistical analysis plan, blank informed consent form, clinical study report, data dictionary, and statistical analysis syntax will also be available. Direct identifiers, signed consent forms, and information that could reasonably identify participants will not be shared. When: Access will begin six months after publication of the main study results and will remain available for five years. To whom: Qualified researchers affiliated with recognized academic, healthcare, or scientific research institutions may request access to the data and documents. Conditions: The data and documents may be used for replication of the study findings, secondary analyses, systematic reviews, or meta analyses after approval of a scientifically and ethically sound proposal. Applicants must provide their institutional affiliation, research proposal, analysis plan, and ethics approval when applicable. They must sign a data use agreement prohibiting participant reidentification, unauthorized use, and onward sharing. Proper acknowledgment and citation of the original study will be required. Where to obtain: Requests should preferably be submitted by email to Mohamadreza Heidarzadeh, Infectious Diseases Resident, Department of Infectious Diseases, Shahid Sadoughi Hospital, Yazd, Iran, at mohamadrezaheidarzadeh0776@gmail.com. Postal correspondence may be sent to the Department of Infectious Diseases, Shahid Sadoughi Hospital, Ebne Sina Boulevard, Shahid Ghandi Boulevard, Safaieh, Yazd, Iran. Telephone: +98 35 38224000. The principal investigator may also be contacted at jamshidayatollahi@yahoo.com. How to obtain: The applicant must submit a written request including their name, institutional affiliation, research question, proposed analyses, requested variables, ethics approval when applicable, funding source, and conflicts of interest. Receipt of the request will be confirmed within seven working days. The research team will review the request within 30 working days and may request additional information. If approved, a data use agreement will be signed and the requested files will be transferred securely within 15 working days after completion of the agreement. The reason for rejection will be communicated to the applicant. Comments: All shared participant data will be coded and deidentified. Access will be limited to the approved applicants, purposes, variables, and access period. The participant identification key and signed consent forms will remain confidential and will not be shared. Data sharing will be subject to the approved informed consent form and applicable ethics committee requirements.
public Mohammadreza Heidarzadeh
Department of Infectious Diseases, Shahid Sadoughi Hospital, Ebne Sina Boulevard, Shahid Ghandi Boulevard, Safaieh
Yazd Iran (Islamic Republic of) 8915887857 +98 35 3822 4000 mohamadrezaheidarzadeh0776@gmail.com Yazd University of Medical Sciences scientific Alireza Haddadi
Department of Infectious Diseases, Shahid Sadoughi Hospital, Ebne Sina Boulevard, Shahid Ghandi Boulevard, Safaieh
Yazd Iran (Islamic Republic of) 8915887857 +98 35 3822 4000 haddadialireza80@gmail.com Yazd University of Medical Sciences Iran (Islamic Republic of) Age 18 years or older Baseline platelet count greater than 150,000 per microliter Hospitalization and a clinical indication for concomitant treatment with linezolid and meropenem for at least 7 days Provision of written informed consent to participate in the study 18 years no limit Both History of hematologic disorders Severe hepatic impairment defined as Child-Pugh class C Severe renal impairment defined as an estimated glomerular filtration rate below 30 mL/min/1.73 m² or need for dialysis Advanced bone marrow failure Concomitant use of medications affecting platelet count such as aspirin or clopidogrel Presence of an underlying cause of thrombocytopenia such as immune thrombocytopenia, bone marrow aplasia, leukemia, hematologic malignancy, known megaloblastic anemia, or hypersplenism Severe sepsis or septic shock with thrombocytopenia before antibiotic administration Concomitant use of piperacillin Active bleeding Recent use of vitamin B12 or folic acid D69.5 Secondary thrombocytopenia Treatment - Drugs Placebo Intervention group: Participants will receive 1,000 micrograms of oral vitamin B12 once daily and 1 milligram of oral folic acid once daily for seven days, starting concurrently with meropenem and linezolid treatment. Standard treatment with meropenem and linezolid will be administered according to the treating physician's judgment and the hospital protocol Control group: Participants will receive matching oral placebo for seven days with the same number of dosage units, appearance, color, size, shape, packaging, and administration schedule as the active supplements. Standard treatment with meropenem and linezolid will be administered according to the treating physician's judgment and the hospital protocol Occurrence of thrombocytopenia, defined as at least one platelet count below 150,000 per microliter after initiation of the intervention. Timepoint: At baseline before initiation of the intervention and on days 3 and 7 after initiation of the intervention. Method of measurement: Platelet count will be measured in a venous blood sample using an automated hematology analyzer as part of a complete blood count. Platelet count expressed as the number of platelets per microliter of venous blood. Timepoint: At baseline before the intervention and on days 3 and 7 after initiation of the intervention. Method of measurement: Measurement in a venous blood sample using an automated hematology analyzer as part of a complete blood count. Severity of thrombocytopenia classified as mild for a platelet count from 100,000 to less than 150,000 per microliter, moderate for a count from 50,000 to less than 100,000 per microliter, and severe for a count below 50,000 per microliter. Timepoint: On days 3 and 7 after initiation of the intervention. Method of measurement: Classification according to platelet count measured in venous blood using an automated hematology analyzer. Discontinuation of linezolid or meropenem due to platelet count reduction, recorded as yes or no. Timepoint: From initiation of the intervention through day 7. Method of measurement: Review of medication orders and the treating physician's documented reason for discontinuation in the medical record. Total duration of hospitalization in days from hospital admission to discharge. Timepoint: At hospital discharge. Method of measurement: Calculation from the admission and discharge dates recorded in the hospital information system and medical record. Occurrence of at least one suspected adverse reaction to the study products, recorded as yes or no. Timepoint: Daily from initiation of the intervention through day 7. Method of measurement: Daily clinical assessment and review of nursing notes, medication records, and the medical record. Yazd University of Medical Sciences Approved 2026-06-16 Research Ethics Committee of the School of Medicine, Shahid Sadoughi University of Medical Sciences School of Medicine, Shahid Sadoughi University of Medical Sciences, Shohadaye Gomnam Boulevard, Alem Square Yazd Yazd Iran (Islamic Republic of)