Evaluation of protective effect of nano-silymarin oral formulation on vancomycin-induced nephrotoxicity

Evaluation of the protective effect of oral nano-silymarin formulation on vancomycin-induced nephrotoxicity

A Phase 3 Triple-blind Parallel Randomized Clinical trial with control group on 60 patients. https://www.sealedenvelope.com was used for randomization.

60 patients in the infectious diseases ward of Imam Reza Hospital who receive vancomycin and meet the inclusion criteria will be included in the study. These patients will be randomly divided into two equal groups of intervention and placebo. The capsules will be identified and distinguished by the number 1-60 and will be placed in the cans by the manufacturer according to the randomization list prepared, 30 patients will take the nano-silymarin capsule and others will take the placebo capsule twice a day. Patients will receive vancomycin for at least 7 days. Serum creatinine and BUN levels will measure on days 0, 3, 7, 10 and day 14 from the start of silymarin administration. In case of renal toxicity, serum creatinine levels will be checked daily. Patients, analysts and therapists will be blind.

Age between 18-60 y, baseline GFR higher than90 ml/min, not receiving concomitant nephrotoxic drugs, no history of allergy to silymarin, not being pregnant or breastfeeding, not taking antioxidant supplements

treatment group: Nano-silymarin 70 mg (softgel sinalive 70mg) capsules prepared by Exir Nanosina Company twice a day (after breakfast and dinner) for 14 days or until vancomycin is discontinued. placebo group: Placebo capsules(without silymarin) prepared by Elixir Nanosina Company, twice a day for 14 days or until vancomycin is discontinued.

Serum creatinine and BUN levels at days 0, 3, 7 ,10 and 14; Serum levels of cystatin C on days 3 and 7

Blocked randomization using website https://www.sealedenvelope.com With the explanation that each block has 4 members and the shape of the blocks can be as follows: [ABAB], [ABBA, [AABB],[BBAA],[BABA][BAAB] Code A belongs to the intervention group and code B belongs to the control group. the mentioned website selects 15 blocks from Quadruple blocks and finally 60 patients will enter the study. Allocation concealment method: Use of the central service, which consists of people who work in the center and have no knowledge of the researchers and will make a secret allocation for the research. In this method, based on the blocks created in the randomization method, a code is considered for each patient, which will be provided to the researcher at the time of patient admission by a person who has no knowledge of the process of studies and statistical analysis.

The capsules will be identified by the number 1-60, which are based on a random list prepared from randomization.com, belonging to the drug or placebo group, and are placed in cans by the manufacturer according to the randomization list prepared. Physicians, patients, and the person analyzing the results will remain unaware of the type of formulation until the work is completed. Patients receive one of the medicine containers with the number 1-60 from the clinical pharmacy resident, respectively. The list will be decrypted when completed. If a new drug, whether related to cancer or not is started for the patient he or she will inform the physician.