Tranexamic Acid for Hip Fracture

Overseen By Kristin Gardner, MSN, RN

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Gregory Georgiadis

Must not be taking: Hormone therapy

Disqualifiers: Seizures, Coagulation abnormality, DVT/PE, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Tranexamic Acid (TXA), a medication used in hip and knee surgeries, can reduce blood loss and the need for blood transfusions in people with hip fractures. Researchers aim to determine if administering TXA before, during, and after surgery benefits these patients. The trial includes two groups: one receives TXA, and the other receives a placebo (a substance with no active medication). Individuals over 60 years old with a hip fracture requiring surgery may be suitable for this trial. As a Phase 4 trial, this research seeks to understand how this already FDA-approved and effective treatment can benefit more patients.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on active hormone therapy, you cannot participate in the trial.

What is the safety track record for Tranexamic Acid (TXA)?

Research has shown that tranexamic acid (TXA) is generally safe for use in hip surgeries. Studies have found that TXA reduces blood loss during hip fracture surgeries, decreasing the need for blood transfusions. This significantly benefits recovery and overall outcomes.

Regarding safety, TXA is well-tolerated by patients. A review of studies found that TXA did not increase serious side effects in elderly patients undergoing hip surgeries. This finding is crucial, as it suggests TXA can be used safely in a group more prone to complications.

Additionally, TXA is already approved for use in other surgeries, such as total hip and knee replacements, further supporting its safety. This approval indicates extensive testing and well-documented safety.

Overall, the evidence supports TXA as a safe option for managing blood loss in hip fracture patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Tranexamic Acid (TXA) is unique because it directly helps to reduce blood loss in patients with hip fractures by stabilizing clots. Unlike traditional treatments that primarily involve managing bleeding with blood transfusions or surgical techniques, TXA works by preventing the breakdown of fibrin, which is crucial for clot stability. Researchers are excited about TXA because it offers a more proactive approach to minimizing blood loss, which can lead to fewer complications and a faster recovery for patients. Additionally, TXA is administered intravenously, ensuring rapid action right where it's needed most.

What evidence suggests that Tranexamic Acid (TXA) might be an effective treatment for hip fracture?

Research has shown that tranexamic acid (TXA), which participants in this trial may receive, helps reduce blood loss during hip fracture surgery. One study found that TXA significantly lowers the need for blood transfusions in these surgeries. Another study demonstrated that a single dose of TXA before surgery effectively reduces both blood loss and the need for transfusions. The benefits of TXA in hip fracture surgeries are clear, particularly in reducing blood loss and lowering the risk of needing a blood transfusion after surgery. ^{2 5 6 7 8}

Who Is on the Research Team?

Gregory M Georgiadis, MD

Principal Investigator

ProMedica Toledo Hospital

Are You a Good Fit for This Trial?

This trial is for individuals over 60 years old with a hip fracture needing surgery. They must consent to participate and not be admitted directly to nursing or surgery from the Emergency Center. Excluded are those under 60, without consent, multiple fractures, poor kidney function, on hormone therapy, coagulation issues, history of seizures or certain blood clots.

Inclusion Criteria

Over the age of 60 years

Signs consent and agrees to participate

You recently had a broken hip that needed surgery to fix it.

Exclusion Criteria

Patients admitted directly to nursing units or surgery without stay in the Emergency Center

Under the age of 60

Does not sign consent or refuses participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Preoperative Treatment

Participants receive either Tranexamic Acid (TXA) or placebo intravenously prior to surgery

8 hours

1 visit (in-person)

Perioperative Treatment

Participants receive additional doses of Tranexamic Acid (TXA) or placebo at the time of incision and three hours later

1 day

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for blood transfusion requirements and anemia

72 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tranexamic Acid (TXA)

Trial Overview

The study tests if Tranexamic Acid (TXA) can reduce the need for blood transfusions after hip fracture surgeries. Participants will receive TXA before, during and after surgery compared to a saline solution group in order to evaluate its effectiveness in controlling blood loss.

How Is the Trial Designed?

Group I: Experimental Arm Experimental Treatment 1 Intervention

Will receive intravenous Tranexamic Acid (TXA) 15mg/kg (maximum 1 gram) bolus dose over 10 minutes in the Emergency Center. The subject will also receive an intravenous dose of Tranexamic Acid (TXA) 15mg/kg over 8 hours prior to surgery. Another 15mg/kg dose of Tranexamic Acid (TXA) will be administered over 10 minutes at the time of incision and the final dose (15mg/kg) of Tranexamic Acid (TXA) intravenously over 10 minutes three hours later.

Group II: Control Arm Placebo Group 1 Intervention

Will receive intravenous Saline solution placebo bolus dose in the Emergency Center over 10 minutes. The subject will also receive intravenous Saline solution over 8 hours prior to surgery. Another dose will be administered at the time of incision and the final dose three hours later.

Tranexamic Acid (TXA) is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Cyklokapron for:

• Heavy menstrual bleeding
• Postpartum hemorrhage
• Bleeding disorders
• Orthopedic surgery

Approved in United States as Lysteda for:

• Heavy menstrual bleeding
• Postpartum hemorrhage
• Bleeding disorders
• Orthopedic surgery

Approved in Japan as Nicolda for:

• Heavy menstrual bleeding
• Postpartum hemorrhage
• Bleeding disorders
• Orthopedic surgery

Who Is Running the Clinical Trial?

Gregory Georgiadis

Lead Sponsor

Trials

1

Recruited

200+

Gregory M Georgiadis MD

Lead Sponsor

Trials

1

Recruited

200+

Published Research Related to This Trial

In a study of 45,290 patients undergoing total hip arthroplasty, the use of tranexamic acid (TXA) did not significantly increase the risk of cardiovascular events or death within 30 days post-surgery.

The analysis, which included propensity score matching, showed no significant differences in risks for venous thromboembolism, myocardial infarction, or all-cause mortality, suggesting that TXA is safe for use in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative Tranexamic Acid Treatment and Risk of Cardiovascular Events or Death After Total Hip Arthroplasty: A Population-Based Cohort Study from National Danish Databases. Dastrup, A., Pottegård, A., Hallas, J., et al.[2019]

Bisphosphonates are commonly prescribed for osteoporosis and are generally considered safe and well-tolerated, but there have been increasing reports of atypical femur fractures associated with long-term use since 2005.

The American Society for Bone and Mineral Research (ASBMR) has highlighted the need for further research to better understand the pathophysiology and epidemiology of these atypical fractures linked to bisphosphonate treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bisphosphonates and atypical fractures of femur. Yli-Kyyny, T.[2021]

Prophylactic administration of tranexamic acid (TXA) before major hip and knee surgeries significantly reduces intra- and postoperative bleeding and the need for blood transfusions, with a number needed to treat (NNT) of 3.7-5.7 for knee replacements and 4.1-8.2 for hip replacements.

The use of TXA does not significantly increase the risk of thromboembolic events compared to placebo, and while there is limited data on the risk of seizures, the doses used in these surgeries are unlikely to cause such complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic Acid Prophylaxis in Hip and Knee Joint Replacement. Goldstein, M., Feldmann, C., Wulf, H., et al.[2018]

FRAX is an effective tool for identifying patients at high risk of fractures, particularly those with glucocorticoid-induced osteoporosis, which can be effectively treated with teriparatide.

Denosumab significantly reduces the risk of various types of fractures, including vertebral, non-vertebral, and hip fractures, while calcium supplementation does not increase cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Osteoporosis]. Uebelhart, B., Rizzoli, R.[2009]

In a study of 796 young patients (ages 18-50) who underwent internal fixation for femoral neck fractures, one-third required at least one reoperation within a median of 16 months, highlighting a significant risk of complications after surgery.

Among those reoperations, 14% of patients were converted to total hip arthroplasty (THA), with a median time to conversion of 2 years, indicating that while internal fixation is common, it may not always be a long-term solution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High rate of reoperation and conversion to total hip arthroplasty after internal fixation of young femoral neck fractures: a population-based study of 796 patients. Stockton, DJ., O'Hara, LM., O'Hara, NN., et al.[2020]

Tranexamic acid (TXA) significantly reduces total blood loss in patients undergoing hip arthroplasty, with a weighted mean difference favoring TXA compared to controls (P<0.001).

While there is a trend towards fewer patients requiring blood transfusions in the TXA group, this result was not statistically significant, indicating that TXA is effective for reducing bleeding but may not drastically lower transfusion needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficiency of tranexamic acid in perioperative blood loss in hip arthroplasty: a systematic literature review and meta-analysis. Pinzón-Florez, CE., Vélez Cañas, KM., Díaz Quijano, DM.[2018]

A 63-year-old woman developed toxic acute tubular necrosis (ATN) after receiving a single dose of zoledronate for osteoporosis, highlighting a rare but serious side effect of this medication.

After discontinuing zoledronate, the patient's renal function improved significantly, indicating that careful monitoring of kidney function is essential to prevent acute renal failure in patients treated with this bisphosphonate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early onset acute tubular necrosis following single infusion of zoledronate. Yachoui, R.[2020]

An 83-year-old woman on long-term bisphosphonate treatment experienced an atypical femur fracture, highlighting a potential risk associated with these medications.

Following surgery for the fracture, she developed a nonunion of the periprosthetic femoral fracture, leading to the discontinuation of bisphosphonate treatment, emphasizing the need for careful monitoring of patients on these drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bisphosphonate-induced Atypical Femoral Shaft Fracture. Baig, MU., Maqbool, A.[2020]

In a study of 78 patients undergoing total hip arthroplasty, both intravenous and intra-articular administration of tranexamic acid (TXA) showed similar effectiveness in reducing postoperative bleeding, with no significant differences in hemoglobin and hematocrit levels between the two groups.

The intra-articular group experienced greater total blood loss compared to the intravenous group, but both methods resulted in a low transfusion rate of 5.1% and no secondary complications, indicating safety in both administration routes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which route of administration of acid tranexamic, intravenous or intra-articular, is more effective in the control of post-surgical bleeding after a total hip arthroplasty? A prospective, controlled and randomized study. Gómez Barbero, P., Gómez Aparicio, MS., Blas Dobón, JA., et al.[2021]

Femoral neck fractures in elderly patients remain difficult to treat, with persistent risks of nonunion and osteonecrosis after surgical fixation, despite improvements in techniques and care over the past 50 years.

There is ongoing uncertainty regarding the best surgical options, such as internal fixation versus various types of arthroplasty, and future advancements in osteoporosis treatment and bone graft substitutes may enhance outcomes for these fractures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Femoral neck fractures. Schmidt, AH., Swiontkowski, MF.[2019]

A study analyzing data from the FDA Adverse Event Reporting System found that bisphosphonate use is associated with a significantly increased risk of nonhealing femoral fractures, with a proportional reporting ratio of 4.51, indicating a strong safety signal.

Most cases of these atypical femoral fractures were linked to alendronate, and up to 26% of reported cases showed delayed healing, prompting safety warnings and label changes from health agencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bisphosphonates and nonhealing femoral fractures: analysis of the FDA Adverse Event Reporting System (FAERS) and international safety efforts: a systematic review from the Research on Adverse Drug Events And Reports (RADAR) project. Edwards, BJ., Bunta, AD., Lane, J., et al.[2021]

A study analyzing adverse cardiac events in over 137,000 users of osteoporosis medications found that teriparatide is associated with fewer coronary artery disease (CAD) and arteriosclerosis coronary artery (ACA) events compared to alendronate and zoledronic acid.

While all osteoporosis medications showed some association with cardiac events, teriparatide was linked primarily to atrial fibrillation and arrhythmias, suggesting it may have a more favorable cardiovascular safety profile than traditional bisphosphonates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac adverse events in bisphosphonate and teriparatide users: An international pharmacovigilance study. Rodríguez, AJ., Nerlekar, N., Ebeling, PR.[2023]

In the HORIZON Recurrent Fracture Trial involving 2,127 patients, intravenous zoledronic acid (ZOL) did not show any clinically significant effect on delayed hip fracture healing, even when administered shortly after surgery.

The incidence of delayed healing was similar between the ZOL group (3.2%) and the placebo group (2.7%), indicating that ZOL can be safely administered without concern for negatively impacting fracture recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between timing of zoledronic acid infusion and hip fracture healing. Colón-Emeric, C., Nordsletten, L., Olson, S., et al.[2022]

Bisphosphonates, particularly alendronate and risedronate, are effective in reducing fracture rates in the spine and hip, making them the most widely prescribed medications for osteoporosis management.

New treatments like denosumab and parathyroid hormone peptides show promise in enhancing bone formation and reducing fractures, with some therapies like teriparatide maintaining benefits even after treatment ends.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developments in the pharmacotherapeutic management of osteoporosis. Close, P., Neuprez, A., Reginster, JY.[2019]

In a study involving 93 patients with high-energy fractures, the use of tranexamic acid (TXA) significantly reduced total blood loss (TBL) compared to the control group, with TBL of 952 mL for TXA versus 1325 mL for no TXA (P = 0.028).

Despite the reduction in blood loss, TXA did not significantly lower overall transfusion rates or increase the risk of venous thromboembolic events (VTE), indicating it is safe to use in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic Acid Use in Open Reduction and Internal Fixation of Fractures of the Pelvis, Acetabulum, and Proximal Femur: A Randomized Controlled Trial. Spitler, CA., Row, ER., Gardner, WE., et al.[2020]

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The goal of this study is to assess if the use of tranexamic acid in patients with hip fractures will result in a reduction in blood losses and blood ...