Evaluation of Misoprostol for Hemorrhagic Risk Reduction in Myomectomy for Uterine Fibroids: A Randomized Controlled Trial

The primary objective of this study is the **evaluation** of intraoperative blood loss during myomectomies with OTAU following the administration of **misoprostol** 400 μg orally in the experimental group compared to a placebo in the control group, irrespective of the surgical technique employed. This objective is clinically relevant as it aims to assess the efficacy of misoprostol in reducing blood loss during surgical procedures for fibroma, potentially improving patient outcomes and reducing the need for blood transfusions.

Secondary objectives include comparisons between the experimental and control groups on various parameters:

• The difference in **haemoglobin** levels between d-1 and d1, and the crude level on d1.
• Patient characteristics.
• Characteristics of fibroids.
• The time interval between tablet administration and incision.
• Total operating time.
• Transfusion rate.
• Immediate postoperative complications.
• Pain assessments at different times using the Visual Analogue Scale (VAS) at h+2, h+6, J1, and M1.
• Length of hospital stay in days.

The clinical trial focuses on evaluating intraoperative blood loss during myomectomies in patients with **fibroma**. The study population consists exclusively of female participants aged 18 to 43 years, who are not considered part of a vulnerable population. Participants are selected based on the presence of symptomatic myomas, such as hemorrhages, pain, or infertility, and have an indication for myomectomy either by laparoscopy or laparotomy, depending on the size and number of fibroids. The trial does not include male subjects, and no information regarding the total number of participants or specific lifestyle considerations, such as diet or physical activity, has been provided by the sponsor.

The clinical trial is designed to evaluate the efficacy of **misoprostol** in reducing intraoperative blood loss during myomectomies in patients with symptomatic **fibroma**. This study is a randomized, double-blind, controlled trial comparing the administration of 400 µg of misoprostol orally to a placebo. The trial is set to commence on October 1, 2024, and is expected to conclude by December 1, 2026. Participants will be randomly assigned to either the experimental group receiving misoprostol or the control group receiving a placebo, with both groups undergoing myomectomy procedures.

The trial will include several key visits: an initial screening visit, follow-up visits, and an end-of-study visit. During the screening visit, eligibility criteria will be assessed, including age (18 to 43 years), presence of symptomatic myomas, and specific indications for myomectomy. Follow-up visits will monitor intraoperative blood loss, hemoglobin levels pre- and post-operatively, and other secondary endpoints such as demographic characteristics, myoma characteristics, and postoperative complications. The end-of-study visit will conclude the participant's involvement in the trial.

Participants are expected to be involved in the study for the duration of their surgical procedure and subsequent follow-up period, which may extend up to one month post-operatively. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The primary endpoint of the study is the measurement of intraoperative blood loss, while secondary endpoints include comparisons of hemoglobin levels, demographic and myoma characteristics, and postoperative outcomes between the two groups.

The clinical trial involves the administration of **Misoprostol**, marketed under the name MisoOne 400 mikrogramų tabletės, as the experimental medication. Misoprostol is a chemically synthesized prostaglandin E1 analog, provided in the form of oral tablets. Each tablet contains 400 micrograms of the active substance. The medication is administered orally, with a maximum daily and total dose of 400 micrograms, intended for a single treatment period. The pharmaceutical form is a standard tablet, and the product is manufactured by EXELGYN SA. The trial aims to evaluate the efficacy of Misoprostol in reducing intraoperative blood loss during myomectomies.

The study also includes a **placebo** as a control treatment. The placebo is provided in the form of coated tablets, identical in appearance to the Misoprostol tablets, but devoid of any active pharmaceutical ingredient. The placebo is administered orally, with no active dose, serving as a comparator to assess the efficacy of the experimental treatment. The placebo is chemically inert and is used to ensure the blinding of the study. Both the experimental and control treatments are administered under the same conditions to maintain consistency in the trial protocol.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint of intraoperative blood loss, measured in milliliters. This measurement will be obtained by calculating the volume in the suction and the blood volumes in the compresses after weighing, according to the randomization group. The trial involves the administration of **misoprostol** 400 µg orally in the experimental group, compared to a placebo in the control group, during myomectomies.

Secondary endpoints will include a variety of comparative analyses based on the randomization group and the type of surgery. These analyses will assess differences in hemoglobin levels pre- and post-operatively, as well as at one month post-operation. Additional comparisons will be made regarding demographic characteristics of patients and fibroids, such as BMI, age, parity, and ethnicity, as well as the characteristics of the myomas, including type, size, and number. The duration between taking the tablet and anesthetic induction, the duration between incision or pneumoperitoneum and closure, and the number of red blood cell transfusions will also be evaluated. Early postoperative complications, pain scores at specified timepoints (H+2, H+6, Day 1, Month 1), and the length of hospitalization in days will be compared.