Evaluation of Tranexamic Acid in Reducing Hemorrhage and Transfusion Requirements in Major Abdominal Surgery: A Randomized Controlled Trial

The primary objective of this trial is to assess whether the intraoperative administration of **Tranexamic Acid** reduces hemorrhage and consequently decreases the need for intra- and postoperative transfusion of packed red blood cells in major abdominal surgeries, such as esophagectomy, gastrectomy, colectomy, rectal resection, pancreatic resection, and hepatectomy. This is clinically relevant as it aims to minimize blood transfusion requirements, which can reduce the risk of transfusion-related complications and improve surgical outcomes.

Secondary objectives include evaluating the amount of intraoperative blood loss, the safety of administering **Tranexamic Acid**, the occurrence of complications post-operation, the length of inpatient hospital stay, and the quality of life. These factors are crucial for understanding the broader impact of **Tranexamic Acid** on patient recovery and overall healthcare resource utilization.

The clinical trial involves participants undergoing major abdominal surgery, including **esophagectomy**, gastrectomy, colectomy, rectal resection, pancreatic resection, and hepatectomy. The study population comprises both male and female subjects aged 18 years and older. Participants are required to have adequate renal function, with serum creatinine levels below 250 μmol/L (2.82 mg/dL). The trial includes individuals who have provided written informed consent and are capable of understanding the nature and consequences of trial participation. Women of childbearing potential must have a negative pregnancy test within 14 days before starting the study treatment and agree to use highly effective contraceptive measures during the study. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on planned elective surgeries and specific health criteria, ensuring a focus on individuals who can safely participate in the study. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **tranexamic acid** in reducing intraoperative and postoperative transfusion requirements in patients undergoing major abdominal surgeries, such as esophagectomy, gastrectomy, colectomy, rectal resection, pancreatic resection, and hepatectomy. This study is a randomized, controlled trial with a double-blind design, ensuring that neither the participants nor the investigators are aware of the treatment allocations. The trial is categorized as a low-intervention study, as both **tranexamic acid** and sodium chloride are authorized medicinal products used according to the conditions approved by the European Medicines Agency (EMA). The trial is expected to commence recruitment on April 1, 2024, and conclude by October 31, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (≥18 years), planned elective surgery, adequate renal function, and informed consent. Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception. The primary endpoint is the transfusion of at least one unit of packed red blood cells (PRBCs) intra- or postoperatively. Secondary endpoints include the number of transfused PRBCs, estimated blood loss, time to transfusion, postoperative complications, hospital stay duration, operation and anesthesia duration, D-dimer levels, and quality of life.

Participants will be involved in the study for a maximum treatment period of one day, with follow-up visits scheduled to monitor outcomes and collect data on secondary endpoints. The end-of-study visit will mark the completion of data collection and participant involvement. 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 trial's methodology and design ensure rigorous assessment of the primary objective while maintaining participant safety and data integrity.

The clinical trial involves the administration of **Tranexamic Acid**, marketed as Tranexamsäure Carinopharm 100mg/ml Injektions-/Infusionslösung. This experimental medication is provided in the form of a **solution for injection/infusion**. The active substance, **tranexamic acid**, is of chemical origin and is utilized to assess its efficacy in reducing hemorrhage during major abdominal surgeries. The medication is administered via **intravenous perfusion**, with a maximum daily dose of 20 ml and a total dose not exceeding 20 ml. The treatment period is limited to a single day. The product is manufactured by Carinopharm GmbH and holds the marketing authorization number 88847.00.00 in Germany.

In addition to the experimental treatment, the trial employs a non-experimental treatment, **Sodium Chloride**, marketed as Isotone Kochsalz-Lösung 0,9 % Braun Infusionslösung. This solution serves as a **placebo** and is also provided in the form of a **solution for injection/infusion**. The active substance, **sodium chloride**, is of chemical origin and is administered via **intravenous perfusion**. The dosing schedule mirrors that of the experimental treatment, with a maximum daily and total dose of 20 ml, administered over a single day. This product is manufactured by B.Braun Melsungen AG and holds the marketing authorization number 6726174.00.00 in Germany.

The efficacy of Tranexamic Acid in reducing hemorrhage and the need for intra- and postoperative transfusion of packed red blood cells (PRBCs) during major abdominal operations will be assessed in this clinical trial. The primary endpoint for evaluating efficacy is the intra- or postoperative transfusion of at least one unit of PRBCs. Secondary endpoints include the number of transfused PRBCs per patient, estimated amount of intraoperative blood loss, time to transfusion, number and severity of postoperative in-hospital complications or mortality (up to 30 days), duration of hospital stay, operation and anesthesia duration, **D-dimer** levels, and quality of life.

Data collection will occur at various timepoints throughout the trial, with specific measurements taken during and after the surgical procedures. The trial is designed as a low-intervention study, as both Tranexamic Acid and normal saline (NaCl 0.9%) are authorized medicinal products used according to the conditions set by the European Medicines Agency (EMA). The trial will adhere to the regulatory framework outlined in Regulation (EU) 536/2014, ensuring that the assessment of efficacy is conducted in a scientifically rigorous manner.