Study design and patients
This prospective, randomized, controlled trial was conducted at the department of orthopaedics of our hospital, and registered in the Chinese Clinical Trial Registry (ChiCTR-1800017761). The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the local Ethics Committee of our hospital (No. S2017-022), and written informed consent and research authorizations were obtained from all participants. All elderly patients with intertrochanteric fractures (age ≥ 65 years, injury time ≤ 6 h) who underwent treatment at the Department of Orthopaedics in the Chongqing General Hospital between September 2018 and September 2019 were prospectively investigated. Inclusion criteria were (1) patients diagnosed with fresh unilateral intertrochanteric fracture and fracture classified according to AO type according to computed radiography or computed tomography; (2) patients aged ≥65 years with intertrochanteric fracture and injury time ≤6 h. Exclusion criteria were (1) patients with injury time > 6 h; (2) those with open fractures, other parts of the body with hemorrhagic wounds, or other areas with bleeding disorders (such as gastrointestinal bleeding); (3) those who exhibited additional fresh fractures in other body parts; (4) patients with recent or ongoing thromboembolic events (deep venous thrombosis, pulmonary embolism, arterial thrombosis, or cerebral thrombosis stroke); (5) patients who were recently taking or who were taking anticoagulation therapy including vitamin K-antagonists, direct thrombin inhibitors, direct factor X-a inhibitors, and platelet aggregation inhibitors; (6) patients with disseminated intravascular coagulation or patients had hepatic or renal diseases with impairment of coagulation function; (7) those receiving conservative treatment; and (8) those with TXA allergy or allergies.
Drug delivery and randomization
Drug delivery and randomization Recruited patients were randomly allocated into two groups (TXA group: IV TXA; NS group: IV NS) based on a computer-generated randomization list, which was generated with use of Randomization.com. The randomization was prepared by a statistician who was not involved in this clinical trial. Patients in the TXA group received i.v. TXA (0.5 g; Ruiyang Pharmaceutical Co., Ltd., Shandong, China) 1 g (200 mL) immediately post-traumatic admission (PTA), and those in the NS group received 200 mL of NS (i.v) immediately PTA. All patients received low-molecular-weight heparin sodium anticoagulation 6 h after injury.
Patient demographic and clinical characteristics, including sex, age, weight, and height, were immediately recorded after admission. Routine blood examination was performed at PTA and on post-traumatic days (PTDs) 1–3 to determine hemoglobin (Hgb) and hematocrit (Hct) levels.
The primary outcomes measures include post-traumatic HBL, the pre-operative transfusion (POT) rate, Hgb drop, Hct change, and the incidence of DVT (Lower-limb venography was performed at the time of three months follow-up if a patient exhibited symptoms of venous thromboembolism) and PE (Computed tomography was taken to examine PE if any suspicious symptom were complained). We used the Gross equation  to calculate post-traumatic HBL: HBL (ml) = PBV × (Hct1 − Hct2), Hct1: Hct level at admission, Hct2: Hct level at a given post-traumatic time point. Patient blood volume (PBV) was calculated using the formula of Nadler et al.  as follows: PBV in males = 0.3669 × height (m)3 + 0.03219 × weight (kg) + 0.6041, PBV in females = 0.356 × height (m)3 + 0.3308 × weight (kg) + 0.1833. The criterion of blood pre-operative transfusion (POT) was as an Hgb level of <80 g/L or symptomatic anemia (light-headedness, palpitation, or shortness of breath not associated with other etiologies) in a patient with an Hgb level of 80–100 g/L .
The secondary outcomes included the length of admission to operation, length of hospital stay, and complications (cardiac infarction, ischemic cerebral infarction, stroke, respiratory infection, and renal failure).
We assumed that this IV-TXA application should reduce hidden blood loss more than 20% compared with control group. Setting the pre-study power of test (β) as 0.9, significant difference (α) as 0.05, and standard effect size of 0.65 indicated that 51 patients were required for each group. To compensate for the expected dropouts (20%), 61 patients per group were planned to include in this study. Calculations were performed with G*Power 3.1.
Data were analyzed using SPSS 21.0 statistical software (SPSS Inc., Chicago, IL, USA), and all relevant data were assessed for normality. Continuous data were analyzed using independent-sample t-tests, and the nonparametric alternative (Mann-Whitney U tests) was used where data were not normally distributed. A chi-square test or Fisher's exact test for difference in proportions was used to estimate differences between groups in categorical variables. The difference was considered statistically significant if P < 0.05.