Clinical trial NCT04696224: Comparative Use of Tranexamic Acid Intravenous and Topical Application in Intertrochanteric Fractures With PFNA
Official title: Comparative Use of Tranexamic Acid Intravenous and Topical Application in the Treatment of Intertrochanteric Fractures With Proximate Femoral Nail
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hemorrhage
Fracture Femur
Keywords: Tranexamic acid
Hemorrhage
Hip fractures
blood transfusion
Lead sponsor: Universidade do Vale do Sapucai
Sponsor class: OTHER
First posted: 2021-01-06
Enrollment: 90
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Primary, analytical, prospective, interventional, double-blind, controlled, randomized study in humans.
Primary purpose: TREATMENT

Brief summary: An intertrochanteric (ITF) trochanteric fracture of the femur is an exclusively extra capsular fracture in which the fracture line extends from the greater trochanter to the lesser trochanter. Its incidence has increased significantly over the past decades and is expected to double in the next 25 years, with an important global economic impact . It affects women in the seventh and eighth decades of life, an age group older than femoral neck fractures. For this reason, the mortality of intertrochanteric fractures is twice that of the femoral neck.

The treatment is surgical, in which the objective is the stable internal fixation and the patient's early ambulation.

Functional outcomes and treatment mortality are related including factors perioperative anemia and blood loss.Even so, even with these precautions, blood loss in this surgical procedure appears to be greater than expected, with blood loss of the order of 2100ml.

Blood loss management and the inherent risks of anemia can be circumvented with blood transfusion. However, blood transfusion is not without risks and complications, such as hypersensitivity and hemolytic reactions, cardiac overload, infectious diseases. Homologous transfusions are associated with prolonged hospital stay, increased costs and increased patient morbidity and mortality.

So, alternatives have been used to avoid the use of blood such as saline solutions, use of erythropoietin and antifibrinolytic agents . Tranexamic acid (TXA) is a drug that interferes with fibrinolysis, in use for more than 50 years in surgery, particularly in cardiac surgery.

Only recently, TXA has sparked interest in orthopedic surgeries. Studies have shown the effectiveness and safety of TXA at FIT, but presented different forms of administration (intravenous, topical, infiltrative) . Despite promising results to contain bleeding in elective orthopedic surgery and fractures, in daily practice, TXA is not very popular, especially in fractures, and has not been used routinely by all doctors. Studies have not been found in the literature about the topical use of TXA compared to intravenous use in FIT.

Detailed description: An intertrochanteric (ITF) trochanteric fracture of the femur is an exclusively extra capsular fracture in which the fracture line extends from the greater trochanter to the lesser trochanter. Usually, it is an isolated fracture, related to osteoporosis, which occurs due to low-energy trauma such as a fall during gait. It is the most common fracture of the proximal femur. Its incidence has increased significantly over the past decades and is expected to double in the next 25 years, with an important global economic impact . It affects women in the seventh and eighth decades of life, an age group older than femoral neck fractures. For this reason, the mortality of intertrochanteric fractures is twice that of the femoral neck.

The treatment is surgical, in which the objective is the stable internal fixation and the patient's early ambulation. The most used materials are plates with dynamic compression screws (Dinamic Hip Screw-DHS) and intramedullary nails (specifically cephalomedullary nails or Proximate femoral nail (PFN). Patients who have suffered this fracture are at high risk for cardiovascular, pulmonary, infections and thrombosis. About a third of patients die in the first year after the injury, approximately 50% become incapable of walking alone or climbing stairs and 20% need permanent home care.

Functional outcomes and treatment mortality are related including factors perioperative anemia and blood loss. In order to prevent blood loss, many strategies have been taken, such as closed or percutaneous fracture reduction and surgical approach with minimally invasive techniques such as fixation with short intramedullary nails (PFN). Even so, even with these precautions, blood loss in this surgical procedure appears to be greater than expected, with blood loss of the order of 2100ml. It was also observed that surgeons underestimate the amount of blood lost in the perioperative period, having estimated a median difference of 1473ml between the apparent blood loss and the one that actually occurred with the use of cephalomedullary nails. Blood loss in ITF is greater than in femoral neck fractures and more often requires blood transfusions.

Blood loss management and the inherent risks of anemia can be circumvented with blood transfusion. However, blood transfusion is not without risks and complications, such as hypersensitivity and hemolytic reactions, cardiac overload, infectious diseases. Homologous transfusions are associated with prolonged hospital stay, increased costs and increased patient morbidity and mortality. Some surgeries may need to wait for the blood supply to be replenished and patients in need of phenotyped blood find it even more difficult and may wait days to weeks before finding their proper blood type.

So, alternatives have been used to avoid the use of blood such as saline solutions, use of erythropoietin and antifibrinolytic agents . Tranexamic acid (TXA) is a drug that interferes with fibrinolysis, in use for more than 50 years in surgery, particularly in cardiac surgery.

Only recently, TXA has sparked interest in orthopedic surgeries. Then it has been used in spine surgery, and joint replacement, without reports of complications. Despite extensive studies on its use in elective orthopedic surgeries, and its high safety profile, there are few studies regarding its use in orthopedic trauma surgery. Studies have shown the effectiveness and safety of TXA at FIT, but presented different forms of administration (intravenous, topical, infiltrative) . Despite promising results to contain bleeding in elective orthopedic surgery and fractures, in daily practice, TXA is not very popular, especially in fractures, and has not been used routinely by all doctors. Studies have not been found in the literature about the topical use of TXA compared to intravenous use in FIT.

Eligibility criteria: Inclusion Criteria:

* Patients of any sex or skin color older than 60 years, admitted for surgical treatment of FIT with indication of fixation with cephalomedullary nails (PFN) in fractures reduced to closed focus.

Exclusion Criteria:

* hypersensitivity to TXA;

  * Thrombocytopenia and coagulation disorders: platelets \<100,000 or prothrombin activity time (TAP) \<70% or activated partial thromboplasty time (APTT)\> 40 seconds or International Standardized List (INR)\> 1;
  * Hepatorenal dysfunction or severe heart disease;
  * Previous surgery in the same place;
  * Use of anticoagulants and corticoids;
  * Pathological fractures of neoplastic origin or duration of neoplastic treatment;
  * Autoimmune disease;
  * History of pulmonary embolism;
  * History of any type of thrombosis (cerebral, in limbs) or stroke;
  * Body Mass Index ≥ 40kg / m2 ;
  * Patients in need of a second surgical access to reduce the fracture with a direct approach to the fracture focus;
  * Diabetes with difficult control.

Primary outcomes:
measure: To assess bleeding loss in operative intertrochanteric fractures
timeFrame: 2 YEARS
Secondary outcomes:
Other outcomes:
Locations:
city: Pouso Alegre
country: Brazil
facility: Hospital das Clinicas Samuel Libanio
state: MG
Study officials:
affiliation: Universidade do Vale do Sapucai
name: Carlos DM ARAÚJO, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Zhou XD, Zhang Y, Jiang LF, Zhang JJ, Zhou D, Wu LD, Huang Y, Xu NW. Efficacy and Safety of Tranexamic Acid in Intertrochanteric Fractures: A Single-Blind Randomized Controlled Trial. Orthop Surg. 2019 Aug;11(4):635-642. doi: 10.1111/os.12511. Epub 2019 Aug 16.
citation: Zhu Q, Yu C, Chen X, Xu X, Chen Y, Liu C, Lin P. Efficacy and Safety of Tranexamic Acid for Blood Salvage in Intertrochanteric Fracture Surgery: A Meta-Analysis. Clin Appl Thromb Hemost. 2018 Nov;24(8):1189-1198. doi: 10.1177/1076029618783258. Epub 2018 Jun 21.
citation: Bostrom J, Grant JA, Fjellstrom O, Thelin A, Gustafsson D. Potent fibrinolysis inhibitor discovered by shape and electrostatic complementarity to the drug tranexamic acid. J Med Chem. 2013 Apr 25;56(8):3273-80. doi: 10.1021/jm301818g. Epub 2013 Apr 10.
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