Combined and Individual Effects of Ursodeoxycholic Acid (UDCA) and Atorvastatin on Gallstone Prevention After Bariatric Surgery: a 2^2 factorial triple-blinded randomised controlled trial

-Determining and comparing the incidence of gallstone formation up to 6 and 12 months after bariatric surgery in atorstatin and UDCA (ursodeoxycholic acid) treatment groups, combined and separately, and the placebo group -Determining and comparing the incidence of stone-related complications and side effects up to 6 and 12 months after bariatric surgery in atorstatin and UDCA combined and separate treatment groups and the placebo group -Determination and comparison of the average changes of liver, kidney, thyroid function tests and lipid profiles during two weeks, 6 and 12 months after bariatric surgery in atorstatin and UDCA combined and separate treatment groups and the placebo group

A randomized, three-blind, placebo-controlled clinical trial with four parallel arms (2^2 factorial design)

The study will be conducted in several bariatric centers of Imam Khomeini and Shariati hospital complex (educational-government) and Erfan hospital (private). The patient, surgeon and radiologist and data analyst will be blinded to the intervention group.

The inclusion criteria include: Adults aged 18 to 65 years who are candidates for RYGB or sleeve gastrectomy (those with a BMI higher than 35 kg/m2 or those with a BMI higher than 30 kg/m2 and with obesity-related diseases) Exclusion criteria include: History of bariatric or gallbladder surgery. Those for whom gallstones have been identified in the preoperative ultrasound

Patients will be divided into four groups receiving different treatments: atorvastatin and UDCA, atorvastatin and UDCA-like placebo, atorvastatin-like placebo and UDCA, and atorvastatin-like placebo and UDCA-like placebo.

Gallstone formation, stone-related complications, type of bariatric surgery, quality of life score

In this study, patients are assigned to treatment groups using a stratified block randomization (block size 8) method using Microsoft Excel software. Treatment groups are first identified in blocks of 8, and then a random number is generated for each patient using the RAND() function. These random values ​​are used to randomly sort the blocks. Patients are assigned sequentially from the randomized list in the order of enrollment to maintain a balance in the number of patients in each group. Treatment groups include UDCA + atorvastatin, UDCA alone, atorvastatin alone, and placebo. Technically, patient allocation is performed at the time of enrollment using the INDEX() function, which assigns a treatment group to a new patient from the randomized list. This method ensures that patients are distributed fairly and without bias to the treatment groups. The study is designed as a triple-blind design, meaning that the patient, the evaluating physician, and the data analyst are unaware of the assigned treatment group. This method in Excel allows for simple and reproducible randomization without the need for complex statistical software. In Excel, randomization is performed by combining the RAND(), SORT(), and INDEX() functions. First, RAND() generates a random number between 0 and 1 for each patient. Then, using the Sort function based on the RAND() values, the order of the patients is randomly changed. After sorting, the INDEX() function is used to assign new patients to one of the treatment groups in the order they arrive. This method is considered a practical and reliable solution for randomization in clinical studies due to its simplicity, high accuracy, and control of balance between groups.

Patients will not know about the type of medicine provided. During each visit, the doctors will not know which type of medical intervention the patient is undergoing, and the radiologist who is responsible for the 6- and 12-month ultrasound is also unaware of the patient's group. The data analyzer will also receive a list of patient groups (1 to 4) in a protected Excel cloud file without ID and specific group type.

Data would be shared after de-identification of shared patients.

Immediately after the results of the final phase of the trial were published.

All researchers provided an acceptable explanation

Any use of data within the framework of the request submitted to our team will be acceptable.

Researchers should contact the corresponding author to access the data. The author's email and contact information are listed at the beginning of this form. shirmohamadi.erf@gmail.com

1. Submission of a complete request for motivation letter and the type of analysis in question on the trial database 2. Providing complete information about the location of the secondary study and the group along with the details of the people involved in the study After studying the necessary information and requesting more information, the group will notify the applicant of the decision within 3 month.