Comparative Use of Tranexamic Acid Intravenous and Topical Application in Intertrochanteric Fractures With PFNA

NCT ID: NCT04696224

Last Updated: 2022-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-18

Study Completion Date

2022-12-18

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hemorrhage Fracture Femur

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary, analytical, prospective, interventional, double-blind, controlled, randomized study in humans.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
For randomization, the computer generated random sequence (BIOESTAT 5.0) will be used. The allocation concealment will be guaranteed by the consecutive opening of numbered, opaque sealed envelopes, after anesthetic induction, opened by the anesthetist, who will be responsible for the intravenous administration and for instructing the nurse of the room about what should be placed in a vat for topical use: saline or tranexamic acid. The orthopedic medical team and the patient will not be aware of which of these will be used intravenously or topically (double blind). The envelopes opened by the anesthetist will have a card written: "intravenous" or "local" or "placebo".

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

INTRAVENOUS

30 patients who will receive 15mg / kg of TXA intravenous in 100ml salina solution (0,9%), after anesthetic induction and before incising the skin (administered in 10 minutes). For masking purposes, these patients will also receive at the end of the surgery, and before performing the plan closure, a compress soaked in 80ml of saline solution (0.9%), which will fill all the plans of the incision, and will be kept for 5 minutes.

Group Type ACTIVE_COMPARATOR

Tranexamic acid

Intervention Type DRUG

The surgical technique consists in patient in supina position with previous reduction with lower limb traction (on a traction table or manual) associated or not with the use of percutaneous reduction clamps. Longitudinal lateral incision of 3-5 cm proximal to the greater trochanter, approximately 5 cm long, will be performed. After the skin and subcutaneous incision, the fascia lata will be incised in the same direction, with exposure of the gluteal muscles and the proximal femur. The awl will be introduced at the tip of the greater trochanter and then, at the same location, an intramedullary guidewire, towards the proximal shaft, crossing the fracture. A 3 cm incision to the thigh and inferior to the initial incision with template to introduce the screw in the center of the femoral head. Then, a 2cm incision will be made at the distal end of the nail, and a hole in the femur for the distal lock in dynamic nail hole with a 4.5mm drill where a cortical screw will be inserted.

LOCAL

30 patients who, at the end of the surgery, and before the suture in layers, will receive a compress soaked in a solution of 1.5 g of tranexamic acid (six ampoules of Transamin®, Zydus Nikkho) diluted in 50 ml of saline solution (0.9 %) (total volume of 80ml), which will fill all the plans of the incision and will be maintained for 5 minutes. For masking purposes, these patients will also receive 100ml of saline solution (0.9%) after anesthetic induction and before incising the skin.

Group Type ACTIVE_COMPARATOR

Tranexamic acid

Intervention Type DRUG

The surgical technique consists in patient in supina position with previous reduction with lower limb traction (on a traction table or manual) associated or not with the use of percutaneous reduction clamps. Longitudinal lateral incision of 3-5 cm proximal to the greater trochanter, approximately 5 cm long, will be performed. After the skin and subcutaneous incision, the fascia lata will be incised in the same direction, with exposure of the gluteal muscles and the proximal femur. The awl will be introduced at the tip of the greater trochanter and then, at the same location, an intramedullary guidewire, towards the proximal shaft, crossing the fracture. A 3 cm incision to the thigh and inferior to the initial incision with template to introduce the screw in the center of the femoral head. Then, a 2cm incision will be made at the distal end of the nail, and a hole in the femur for the distal lock in dynamic nail hole with a 4.5mm drill where a cortical screw will be inserted.

PLACEBO

30 patients who will not receive the TXA, but will receive a 100ml intravenous saline solution 0,9% after anesthetic induction and before incising the skin (such as group 1) and a compress soaked in saline solution as used in group 2.

Group Type PLACEBO_COMPARATOR

Saline solution

Intervention Type OTHER

30 patients who will not receive the TXA, but will receive a 100ml intravenous saline solution 0,9% after anesthetic induction and before incising the skin (such as group 1) and a compress soaked in saline solution as used in group 2

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Tranexamic acid

The surgical technique consists in patient in supina position with previous reduction with lower limb traction (on a traction table or manual) associated or not with the use of percutaneous reduction clamps. Longitudinal lateral incision of 3-5 cm proximal to the greater trochanter, approximately 5 cm long, will be performed. After the skin and subcutaneous incision, the fascia lata will be incised in the same direction, with exposure of the gluteal muscles and the proximal femur. The awl will be introduced at the tip of the greater trochanter and then, at the same location, an intramedullary guidewire, towards the proximal shaft, crossing the fracture. A 3 cm incision to the thigh and inferior to the initial incision with template to introduce the screw in the center of the femoral head. Then, a 2cm incision will be made at the distal end of the nail, and a hole in the femur for the distal lock in dynamic nail hole with a 4.5mm drill where a cortical screw will be inserted.

Intervention Type DRUG

Saline solution

30 patients who will not receive the TXA, but will receive a 100ml intravenous saline solution 0,9% after anesthetic induction and before incising the skin (such as group 1) and a compress soaked in saline solution as used in group 2

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

surgery

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Universidade do Vale do Sapucai

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Carlos Delano Mundim Araujo

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Carlos DM ARAÚJO, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Universidade do Vale do Sapucai

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Hospital das Clinicas Samuel Libanio

Pouso Alegre, Minas Gerais, Brazil

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Brazil

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

LARISSA M BARROS, MD

Role: CONTACT

+5511987635825

THALITA AP MAMEDES

Role: CONTACT

3534499269

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

ANA LAURA

Role: primary

3534293200

References

Explore related publications, articles, or registry entries linked to this study.

Foss NB, Kehlet H. Hidden blood loss after surgery for hip fracture. J Bone Joint Surg Br. 2006 Aug;88(8):1053-9. doi: 10.1302/0301-620X.88B8.17534.

Reference Type BACKGROUND
PMID: 16877605 (View on PubMed)

Henry DA, Carless PA, Moxey AJ, O'Connell D, Stokes BJ, Fergusson DA, Ker K. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2011 Mar 16;2011(3):CD001886. doi: 10.1002/14651858.CD001886.pub4.

Reference Type BACKGROUND
PMID: 21412876 (View on PubMed)

Lei J, Zhang B, Cong Y, Zhuang Y, Wei X, Fu Y, Wei W, Wang P, Wen S, Huang H, Wang H, Han S, Liu S, Zhang K. Tranexamic acid reduces hidden blood loss in the treatment of intertrochanteric fractures with PFNA: a single-center randomized controlled trial. J Orthop Surg Res. 2017 Aug 15;12(1):124. doi: 10.1186/s13018-017-0625-9.

Reference Type BACKGROUND
PMID: 28810918 (View on PubMed)

Mohib Y, Rashid RH, Ali M, Zubairi AJ, Umer M. Does tranexamic acid reduce blood transfusion following surgery for inter-trochanteric fracture? A randomized control trial. J Pak Med Assoc. 2015 Nov;65(11 Suppl 3):S17-20.

Reference Type BACKGROUND
PMID: 26878513 (View on PubMed)

Tengberg PT, Foss NB, Palm H, Kallemose T, Troelsen A. Tranexamic acid reduces blood loss in patients with extracapsular fractures of the hip: results of a randomised controlled trial. Bone Joint J. 2016 Jun;98-B(6):747-53. doi: 10.1302/0301-620X.98B6.36645.

Reference Type BACKGROUND
PMID: 27235515 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31419080 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29929380 (View on PubMed)

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.

Reference Type RESULT
PMID: 23521080 (View on PubMed)

Diaz AR, Navas PZ. Risk factors for trochanteric and femoral neck fracture. Rev Esp Cir Ortop Traumatol (Engl Ed). 2018 Mar-Apr;62(2):134-141. doi: 10.1016/j.recot.2017.09.002. Epub 2018 Feb 21. English, Spanish.

Reference Type RESULT
PMID: 29429857 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

38830520.3.0000.5102

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.