Safety and Efficacy of Oral TXA in Reducing Blood Loss and Transfusion in Hip Fractures

• Sponsor: Yale University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02908516
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arms: 2
• Actual Duration (Months): 2.9
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess the safety and efficacy of Tranexamic acid (TXA) in reducing blood loss and transfusion requirements for patients with osteoporotic hip fractures. In addition to assessing blood loss in these patients, complications associated with TXA use would be characterized including systemic (pulmonary embolism, deep venous thrombosis, myocardial infarction, stroke) and surgical site (hematoma, infection) events, need for re-hospitalization or re-operation and 30 day mortality.

Condition or Disease	Intervention/Treatment	Phase
Hip Fractures; Blood Loss	Drug: Tranexamic Acid; Drug: Placebo	Phase 4

Detailed Description

Hip fractures are associated with significant blood loss and a subsequent need for blood transfusion. The causes of bleeding are multifactorial, increased fibrinolytic activity being one of them. The use of allogenic blood products is expensive and is associated with increased risk of hemolytic and anaphylactic reactions, post-operative infections and lengthened hospital stay. Tranexamic acid (TXA) is a simple and inexpensive pharmacological agent that inhibits fibrinolysis and reduced bleeding. It has a 44 year history of clinical use beginning with patients with symptomatic menorrhagia as well as bleeding prophylaxis in hemophiliac patients undergoing tooth extraction

Tranexamic acid (TXA) is an antifibrinolytic medication (reduces the destruction of blood clots, thus promoting the ability to stop bleeding) that is frequently used to reduce perioperative blood loss, blood transfusions and associated costs in major cardiac, vascular, obstetric, and orthopedic procedures. It has been used successfully in orthopedics to reduce perioperative blood loss, particularly in spine surgery, total knee and total hip arthroplasty (THA). Multiple recent meta-analyses have found that use of TXA in the setting of total knee arthroplasty (TKA) and THA leads to significantly less overall blood loss and lower rates of blood transfusion without increasing rates of venous thromboembolism (VTE) or other complications.

Osteoporotic hip fractures are at an increased risk than elective orthopaedic surgery patients because they are exposed to a double bleeding insult. Fractures bleed and many of these patients sustain their first hit when hematoma forms in their soft tissues leading to symptomatic anemia. Subsequently these patients sustain additional blood loss when they undergo surgery for definitive treatment of their injuries.

Trauma surgeons understand the risk of hemorrhage associated with trauma and routinely give TXA to patients who present with high energy injuries. The CRASH-2 trial was an international study which randomized 20,000 bleeding trauma patients to get TXA or matching placebo upon presentation. With 99.5% follow up, the authors noted a decreased risk of bleeding and death without ill effect.

However, there are limited data on its use in patients with hip fractures. We propose a double-blinded, randomized, controlled trial comparing perioperative administration of TXA to placebo in the setting of femur fractures. Thus our goal is to examine the safety and efficacy of TXA in reducing blood loss and red blood cell requirement for patients with intertrochanteric, subtrochanteric femur fractures at the time of hospital admission.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Safety and Efficacy of Oral Tranexamic Acid in Reducing Blood Loss and Transfusion in Femoral Neck, Intertrochanteric and Subtrochanteric Femur Fractures 100 FR 1 (2015-2)
• Actual Study Start Date: Sep 18, 2017
• Actual Primary Completion Date: Nov 14, 2017
• Actual Study Completion Date: Dec 15, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tranexamic acid Study subjects randomized to receive the TXA group will receive 3 oral capsules of 650 mg each of TXA for a total of 1.95 g. One dose will be given upon diagnosis of a hip fracture in the emergency department (ED) and a second dose will be given two hours prior to surgical incision.	Drug: Tranexamic Acid; 2 doses of 1.95 g TXA orally, once in the ED and another dose pre-operatively.
Placebo Comparator: Placebo Study subjects randomized to the placebo group will receive an equivalent dose of cellulose in 3 oral capsules. One dose will be given upon diagnosis of a hip fracture in the ED and a second dose will be given two hours prior to surgical incision.	Drug: Placebo; 2 doses of 1.95 g cellulose orally, once in the ED and another dose pre-operatively.

Outcome Measures

Primary Outcome Measures

1. Total Blood Loss [Postoperative day 3]

2. Change in Hemoglobin Level [From presentation until postoperative day 3]

3. Number of Transfusion Events [Postoperative day 3]

Secondary Outcome Measures

1. Hospital Length of Stay [During hospitalization, likely less than 1 week]

2. Complications [6 weeks]

   Data were not collected post surgery due to study termination.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Patients presenting with femoral neck, intertrochanteric and subtrochanteric femur fractures Patients age 18 and older Low energy injury

Exclusion Criteria:

Pregnant or breast-feeding women Allergy to tranexamic acid Acquired disturbances of color vision Thrombophilia Antithrombin deficiency Factor V Leiden Antiphospholipid Syndrome Protein C and S deficiency History of heparin induced thrombocytopenia Sickle cell anemia Myeloproliferative disorders International Normalized Ratio (INR) > 1.4 Partial Thromboplastin Time (PTT) > 1.4 times normal A history of arterial or venous thromboembolism Cerebral Vascular Accident Deep Vein Thrombosis Pulmonary Embolism Subarachnoid hemorrhage Active intravascular clotting Participation in another clinical trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale New Haven Hospital	New Haven	Connecticut	United States	06515

Sponsors and Collaborators

• Yale University

Investigators

• Principal Investigator: Michael P Leslie, DO, Yale University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 21, 2016

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT02908516
• Other Study ID Numbers: 2000020122
• First Posted: Sep 21, 2016
• Last Update Posted: Jul 29, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hemorrhage; Fractures, Bone; Hip Fractures; Tranexamic Acid

Study Results

Participant Flow

Arm/Group Title	Tranexamic Acid	Placebo
Arm/Group Description	Study subjects randomized to receive the TXA group will receive 3 oral capsules of 650 mg each of TXA for a total of 1.95 g. One dose will be given upon diagnosis of a hip fracture in the emergency department (ED) and a second dose will be given two hours prior to surgical incision. Tranexamic Acid: 2 doses of 1.95 g TXA orally, once in the ED and another dose pre-operatively.	Study subjects randomized to the placebo group will receive an equivalent dose of cellulose in 3 oral capsules. One dose will be given upon diagnosis of a hip fracture in the ED and a second dose will be given two hours prior to surgical incision. Placebo: 2 doses of 1.95 g cellulose orally, once in the ED and another dose pre-operatively.
Period Title: Overall Study
STARTED	3	3
COMPLETED	0	0
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	Tranexamic Acid	Placebo	Total
Arm/Group Description	Study subjects randomized to receive the TXA group will receive 3 oral capsules of 650 mg each of TXA for a total of 1.95 g. One dose will be given upon diagnosis of a hip fracture in the emergency department (ED) and a second dose will be given two hours prior to surgical incision. Tranexamic Acid: 2 doses of 1.95 g TXA orally, once in the ED and another dose pre-operatively.	Study subjects randomized to the placebo group will receive an equivalent dose of cellulose in 3 oral capsules. One dose will be given upon diagnosis of a hip fracture in the ED and a second dose will be given two hours prior to surgical incision. Placebo: 2 doses of 1.95 g cellulose orally, once in the ED and another dose pre-operatively.	Total of all reporting groups
Overall Participants	3	3	6
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	3 100%	3 100%	6 100%
Sex: Female, Male (Count of Participants)
Female	1 33.3%	2 66.7%	3 50%
Male	2 66.7%	1 33.3%	3 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	3 100%	3 100%	6 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	6 100%

Outcome Measures

1. Primary Outcome

Title	Total Blood Loss
Time Frame	Postoperative day 3

Outcome Measure Data

Analysis Population Description

Data were not collected post surgery due to study termination.

Arm/Group Title	Tranexamic Acid	Placebo
Arm/Group Description	Study subjects randomized to receive the TXA group will receive 3 oral capsules of 650 mg each of TXA for a total of 1.95 g. One dose will be given upon diagnosis of a hip fracture in the emergency department (ED) and a second dose will be given two hours prior to surgical incision. Tranexamic Acid: 2 doses of 1.95 g TXA orally, once in the ED and another dose pre-operatively.	Study subjects randomized to the placebo group will receive an equivalent dose of cellulose in 3 oral capsules. One dose will be given upon diagnosis of a hip fracture in the ED and a second dose will be given two hours prior to surgical incision. Placebo: 2 doses of 1.95 g cellulose orally, once in the ED and another dose pre-operatively.
Measure Participants	0	0

2. Primary Outcome

Title	Change in Hemoglobin Level
Time Frame	From presentation until postoperative day 3

Outcome Measure Data

Analysis Population Description

Data were not collected post surgery due to study termination.

Arm/Group Title	Tranexamic Acid	Placebo
Arm/Group Description	Study subjects randomized to receive the TXA group will receive 3 oral capsules of 650 mg each of TXA for a total of 1.95 g. One dose will be given upon diagnosis of a hip fracture in the emergency department (ED) and a second dose will be given two hours prior to surgical incision. Tranexamic Acid: 2 doses of 1.95 g TXA orally, once in the ED and another dose pre-operatively.	Study subjects randomized to the placebo group will receive an equivalent dose of cellulose in 3 oral capsules. One dose will be given upon diagnosis of a hip fracture in the ED and a second dose will be given two hours prior to surgical incision. Placebo: 2 doses of 1.95 g cellulose orally, once in the ED and another dose pre-operatively.
Measure Participants	0	0

3. Primary Outcome

Title	Number of Transfusion Events
Time Frame	Postoperative day 3

Outcome Measure Data

Analysis Population Description

Data were not collected post surgery due to study termination.

Arm/Group Title	Tranexamic Acid	Placebo
Arm/Group Description	Study subjects randomized to receive the TXA group will receive 3 oral capsules of 650 mg each of TXA for a total of 1.95 g. One dose will be given upon diagnosis of a hip fracture in the emergency department (ED) and a second dose will be given two hours prior to surgical incision. Tranexamic Acid: 2 doses of 1.95 g TXA orally, once in the ED and another dose pre-operatively.	Study subjects randomized to the placebo group will receive an equivalent dose of cellulose in 3 oral capsules. One dose will be given upon diagnosis of a hip fracture in the ED and a second dose will be given two hours prior to surgical incision. Placebo: 2 doses of 1.95 g cellulose orally, once in the ED and another dose pre-operatively.
Measure Participants	0	0

4. Secondary Outcome

Title	Hospital Length of Stay
Time Frame	During hospitalization, likely less than 1 week

Outcome Measure Data

Analysis Population Description

Data were not collected post surgery due to study termination.

Arm/Group Title	Tranexamic Acid	Placebo
Arm/Group Description	Study subjects randomized to receive the TXA group will receive 3 oral capsules of 650 mg each of TXA for a total of 1.95 g. One dose will be given upon diagnosis of a hip fracture in the emergency department (ED) and a second dose will be given two hours prior to surgical incision. Tranexamic Acid: 2 doses of 1.95 g TXA orally, once in the ED and another dose pre-operatively.	Study subjects randomized to the placebo group will receive an equivalent dose of cellulose in 3 oral capsules. One dose will be given upon diagnosis of a hip fracture in the ED and a second dose will be given two hours prior to surgical incision. Placebo: 2 doses of 1.95 g cellulose orally, once in the ED and another dose pre-operatively.
Measure Participants	0	0

5. Secondary Outcome

Title	Complications
Description	Data were not collected post surgery due to study termination.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Data were not collected post surgery due to study termination.

Arm/Group Title	Tranexamic Acid	Placebo
Arm/Group Description	Study subjects randomized to receive the TXA group will receive 3 oral capsules of 650 mg each of TXA for a total of 1.95 g. One dose will be given upon diagnosis of a hip fracture in the emergency department (ED) and a second dose will be given two hours prior to surgical incision. Tranexamic Acid: 2 doses of 1.95 g TXA orally, once in the ED and another dose pre-operatively.	Study subjects randomized to the placebo group will receive an equivalent dose of cellulose in 3 oral capsules. One dose will be given upon diagnosis of a hip fracture in the ED and a second dose will be given two hours prior to surgical incision. Placebo: 2 doses of 1.95 g cellulose orally, once in the ED and another dose pre-operatively.
Measure Participants	0	0

Adverse Events

Time Frame	Adverse events data were not collected and analyzed due to study termination.
Adverse Event Reporting Description	Data, including post surgical adverse events, were not collected post surgery due to study termination.
Arm/Group Title	Tranexamic Acid		Placebo
Arm/Group Description	Study subjects randomized to receive the TXA group will receive 3 oral capsules of 650 mg each of TXA for a total of 1.95 g. One dose will be given upon diagnosis of a hip fracture in the emergency department (ED) and a second dose will be given two hours prior to surgical incision. Tranexamic Acid: 2 doses of 1.95 g TXA orally, once in the ED and another dose pre-operatively.		Study subjects randomized to the placebo group will receive an equivalent dose of cellulose in 3 oral capsules. One dose will be given upon diagnosis of a hip fracture in the ED and a second dose will be given two hours prior to surgical incision. Placebo: 2 doses of 1.95 g cellulose orally, once in the ED and another dose pre-operatively.
All Cause Mortality
	Tranexamic Acid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Tranexamic Acid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Tranexamic Acid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.