One Versus Two Doses of Tranexamic Acid in Surgically Treated Extracapsular Hip Fractures

Prophylactic Administration of One Versus Two Doses of Tranexamic Acid in Surgically Treated Patients With Pertrochanteric and Subtrochanteric Femoral Fractures

The goal of this clinical trial is to learn whether giving one dose or two doses of tranexamic acid can safely lower blood loss in older adults having surgery for certain hip fractures. The study includes adults aged 65 years or older who need surgery for pertrochanteric or subtrochanteric hip fractures.

The main questions the study aims to answer are:

• Does giving two doses of tranexamic acid lower the need for blood transfusions compared to one dose?
• Does tranexamic acid help keep hemoglobin levels higher after surgery?
• Is tranexamic acid safe in this group of participants? Researchers will compare participants who receive one dose of tranexamic acid with those who receive two doses to see which approach works better and is safe.

Participants will:

• Receive either one dose of tranexamic acid before surgery or two doses, one before and one after surgery
• Have standard surgery to fix their hip fracture within 48 hours of hospital admission
• Be monitored during their hospital stay for blood loss, transfusions, and medical problems
• Be followed for up to 90 days after surgery to check for safety A total of 120 participants will take part in this study, which is being conducted at the University Clinic "St. Naum Ohridski" in Skopje, North Macedonia.

This prospective, randomized,single-center clinical study is conducted at the University Clinic for Surgical Diseases "St. Naum Ohridski." Adults aged 65 years or older with pertrochanteric or subtrochanteric femoral fractures are eligible. All patients undergo surgery within 48 hours of admission, according to current recommendations for treatment of pertrochanteric and subtrochanteric fractures. Fractures are classified according to the AO/OTA system by at least two trauma surgeons; discrepancies are resolved by discussion.

Routine preoperative evaluation is performed according to institutional standards and may include patient history, physical examination, standard imaging (X-ray of the pelvis and affected hip, with additional CT scans if indicated), laboratory tests including complete blood count, biochemistry, and coagulation tests, as well as anesthesia assessment. Relevant comorbidities and chronic medications are recorded.

Eligible participants are randomly assigned to one of two treatment groups. One group receives a single prophylactic dose of tranexamic acid, while the other receives two doses according to the study protocol. All participants receive standard surgical and anesthetic care in accordance with institutional practice.

Surgical Procedure:

Surgery is performed under spinal or general anesthesia. Stable pertrochanteric fractures are treated with DHS or short intramedullary nail. Unstable pertrochanteric and subtrochanteric fractures are treated with intramedullary nailing. Reduction may be open or closed, with fluoroscopic guidance. Wound closure is standard; drain placement is at surgeon discretion.

Blood Loss Measurement:

Intraoperative visible blood loss (VBLop) is calculated as suction volume minus irrigation fluids plus blood in sponges, visually estimated.Total visible blood loss (VBL) is the sum of VBLop and drain output. Total blood loss (TBL) is calculated using standard formulas based on preoperative and postoperative hematocrit and red blood cell transfusions. Blood volume is calculated using standard formulas. Hidden blood loss (HBL) is calculated as total blood loss minus visible blood loss (TBL minus VBL).

Red blood cell transfusions are given if hemoglobin is less than 8 grams per deciliter or if symptomatic anemia occurs.

Postoperative Monitoring:

Laboratory tests (Hb, Hct, urea, creatinine, electrolytes) are measured 6 hours postoperatively, then daily up to day 3, or longer if clinically indicated.. Blood products administered per clinical indication. Early mobilization usually on post-op day 1-2. Intensive care unitstay and total hospitalization recorded.

All patients will receive antibiotic prophylaxis according to the institutional protocol. Thromboprophylaxis will be administered using a combined approach, including pharmacologic measures (enoxaparin or an oral anticoagulant if indicated) and mechanical measures (high-compression stockings until full mobilization). Adverse events and complications will be monitored and documented during hospitalization and up to 90 days postoperatively. Routine postoperative assessments, including clinical examination, laboratory tests, and radiographic imaging, will follow standard clinical practice. Additional diagnostic procedures, such as ECG, biochemical markers, Doppler ultrasound, or radiography, will be performed as clinically indicated by the operating surgeon, on-call physician, anesthesiologist, internist, or other relevant specialists, based on the patient's condition. Major adverse events include cerebrovascular events, myocardial infarction, pulmonary embolism, deep vein thrombosis, bowel ischemia, and convulsions. Minor events include nausea, vomiting, headache, and abdominal pain. Surgical complications encompass reoperation for bleeding, hematoma, wound infection, wound healing issues, implant problems (cut-out or malposition), delayed union, malunion, and avascular necrosis. General complications include pneumonia, urinary tract infection, renal insufficiency, drug allergy, and decubitus ulcers. Mortality will be recorded at 30 and 90 days postoperatively.

Patients are followed with outpatient visits at 14 days, 1 month, 2 months, 3 months. Clinical and radiographic evaluation. All complications and adverse events documented.

Data are entered into a secure, anonymized electronic database with predefined variables, units, and normal ranges.Range and consistency checks are performed to ensure data validity.All preoperative, intraoperative, and postoperative data are verified against medical records.Missing or unavailable data are documented and handled according to standard statistical practices. Standard clinical procedures are followed for patient recruitment, data collection, adverse event monitoring, and reporting.

Sample Size: A total of 120 participants (60 per group) are enrolled, sufficient to detect clinically meaningful differences in blood loss and transfusion requirements.

Statistical Analysis Data analysis will be performed using SPSS software (version 25.0; IBM, SPSS, USA). Normality of data distribution will be assessed using the Kolmogorov-Smirnov and Shapiro-Wilk tests.

Categorical (nominal) variables will be presented as counts and percentages. Continuous (quantitative) variables will be presented as mean ± standard deviation, minimum and maximum values, median, and interquartile range.Comparisons between the single-dose and two-dose tranexamic acid groups will be performed as follows: categorical variables- Chi-square test or Fisher exact test, as appropriate, continuous variables (independent samples)- Student's t-test or Mann-Whitney test, depending on data distribution, repeated measures / paired data-Student's t-test for dependent samples, Wilcoxon matched-pairs test, repeated measures ANOVA, or Friedman ANOVA, as appropriate.

Subgroup analyses will be performed according to the type of osteosynthesis (dynamic hip screw or intramedullary fixation) and dosing group for all evaluated outcomes, including incidence of allogeneic transfusion, hemoglobin drop, total and hidden blood loss, total transfused blood volume, length of hospital stay, thrombotic events, and mortality.

Statistical significance will be defined at p less than 0.05.

Inclusion Criteria:

• Written informed consent obtained
• Patients aged 65 years or older
• Patients with pertrochanteric femoral fracture (AO/OTA classification: 31A1.2, 31A1.3, 31A2, 31A3) or subtrochanteric femoral fracture (AO/OTA classification: 32; fractures from the level of the lesser trochanter to 5 cm distally)
• Surgical treatment performed within 48 hours of hospital admission

Exclusion Criteria:

• Age younger than 65 years
• Known allergy or hypersensitivity to tranexamic acid
• Active thromboembolic event (deep vein thrombosis, arterial thrombosis, pulmonary embolism) or history of vascular event within the past year (myocardial infarction, coronary or peripheral vascular stenting, thromboembolism, stroke)
• Impaired renal function defined as serum creatinine >120 µmol/L in the last preoperative laboratory test
• History of malignant disease
• History of seizure disorder or chronic anticonvulsant therapy
• Polytrauma or multiple trauma
• More than one fracture
• Previous fracture of the same hip
• Preoperative hemoglobin level <8 g/dL (last laboratory test before surgery)
• Thrombocytopenia or other coagulation disorders
• Treatment with vitamin K antagonists with INR >1.5
• Treatment with low-molecular-weight heparins without appropriate preoperative discontinuation according to clinical protocol (usually ≥24 hours for prophylactic doses and ≥24-36 hours for therapeutic doses)
• Treatment with direct oral anticoagulants without appropriate preoperative discontinuation (usually 24-48 hours, depending on renal function and bleeding risk)
• Treatment with P2Y12 inhibitors (e.g., ticagrelor, clopidogrel, prasugrel) when, according to anesthesiologist assessment, surgery cannot be safely performed within 48 hours