Randomized Controlled Trial of Tranexamic Acid in Total Knee Arthroplasty: Intravenous vs. Topical

• Sponsor: Hospital for Special Surgery, New York (Other)
• Overall Status: Completed
• CT.gov ID: NCT01940523
• Collaborator: Mayo Clinic (Other)
• Enrollment: 640
• Locations: 2
• Arms: 2
• Actual Duration (Months): 48.5
• Patients Per Site: 320
• Patients Per Site Per Month: 6.6

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether topical or intravenous administration of tranexamic acid during unilateral total knee replacement is more effective at reducing bleeding in the first 24 hours following surgery. Tranexamic acid is a synthetic drug that has been shown to reduce blood drain output and the need for blood transfusions in both its topical and intravenous forms and is commonly used in orthopedic surgery. We hypothesize that IV and topical administration of tranexamic acid will be equally good at reducing the loss of blood and the need for transfusion immediately following total knee replacement.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis	Drug: Topical Tranexamic Acid; Drug: Intravenous Tranexamic Acid	Phase 4

Detailed Description

This randomized controlled trial compares the blood loss of patients undergoing unilateral total knee replacements who randomly receive either the topical or the intravenous form of tranexmamic acid during surgery. Patients in the intravenous arm of the study will receive 1 gram of tranexamic acid in 10 milliliters of solution prior to inflation of the tourniquet and 1 gram of tranexamic acid in 10 milliliters of solution during closure. For patients in the topical arm of the study, prior to the release of the tourniquet they will receive 3 grams of tranexamic acid in 75ccs of solution directly on the site of the incision.

The primary result measurement will be blood drain output from the knee at 24 hours after surgery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 640 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Controlled Trial of Tranexamic Acid in Total Knee Arthroplasty: Intravenous vs. Topical
• Actual Study Start Date: May 1, 2013
• Actual Primary Completion Date: Dec 28, 2015
• Actual Study Completion Date: May 16, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Topical Tranexamic Acid 3 vials of tranexamic acid (1g tranexamic acid in 10cc each) must be mixed in the operating room by the team at the start of surgery with 45cc of saline solution (for a total of 3g tranexamic acid in 75mL solution). This solution will be applied to the open joint surfaces with two 60mL syringes (one with 60mL and one with 15m). The solution will be left in contact with the tissues for five minutes. The surgeon will suction away excess solution. The site may be irrigated before or after the tranexamic acid bath as long as the solution is in contact for at least five full minutes. After that, the tourniquet will be released and the rest of the surgery will proceed according to the standard of care.	Drug: Topical Tranexamic Acid; 3 vials of tranexamic acid (1g tranexamic acid in 10cc each) must be mixed in the operating room by the team at the start of surgery with 45cc of saline solution (for a total of 3g tranexamic acid in 75mL solution). This solution will be applied to the open joint surfaces with two 60mL syringes (one with 60mL and one with 15m). The solution will be left in contact with the tissues for five minutes. The surgeon will suction away excess solution. The site may be irrigated before or after the tranexamic acid bath as long as the solution is in contact for at least five full minutes. After that, the tourniquet will be released and the rest of the surgery will proceed according to the standard of care.
Active Comparator: Intravenous Tranexamic Acid 1 vial (1g of IV tranexamic acid in 10mL solution) will be administered prior to inflation of the tourniquet. A second 1g dose of IV tranexamic acid will be given during initiation of the closure after the tourniquet is deflated and during closure.	Drug: Intravenous Tranexamic Acid; 1 vial (1g of IV tranexamic acid in 10mL solution) will be administered prior to inflation of the tourniquet. A second 1g dose of IV tranexamic acid will be given during initiation of the closure after the tourniquet is deflated and during closure.

Outcome Measures

Primary Outcome Measures

1. Total Blood Loss [during surgery]

   The amount of blood lost during surgery is the primary outcome measure. Blood loss is determineusing an equation that calculates the patient's blood volume based on their height and weight, then multiplies the patient's blood volume by the change in their hematocrit after surgery compared to before surgery.

Secondary Outcome Measures

1. Drain Output [from end of surgery to 24 hours postoperatively]

   The amount of blood collected by a drain attached to the knee is measured 24 hours after surgery.

2. The Number Patients Requiring a Transfusion [over course of hospital stay (averaging three days)]

   TThe number Patients requiring a transfusion over the course of the patient's hospital stay.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Primary total knee replacmeent

• Osteoarthritis

• Unilateral

Exclusion Criteria:

• Revision surgery

• Donated preoperative autologous blood

• On chronic anticoagulation medication such as Coumadin, Xarelto, Plavix, or Aspirin (other than 81mg)

• Preoperative hepatic or renal dysfunction

• Diagnosis of inflammatory disease

• Diagnosis of inflammatory arthritis

• Pregnant

• Breastfeeding

• Preoperative hemoglobin <10g/dL

• International Normalized Ratio>1.4

• Abnormal Partial Thromboplastin Time

• Preoperative platelet count of <150,000mm^3

• Creatinine > 1.4

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55902
2	Hospital for Special Surgery	New York	New York	United States	10021

Sponsors and Collaborators

• Hospital for Special Surgery, New York
• Mayo Clinic

Investigators

• Principal Investigator: David Mayman, MD, Hospital for Special Surgery, New York

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hospital for Special Surgery, New York
• ClinicalTrials.gov Identifier: NCT01940523
• Other Study ID Numbers: 12166; NCT02123095
• First Posted: Sep 12, 2013
• Last Update Posted: Nov 27, 2019
• Last Verified: Nov 1, 2019

• Keywords provided by Hospital for Special Surgery, New York: total knee arthroplasty; total knee replacement; tranexamic acid; osteoarthritis; degenerative joint disease
• Additional relevant MeSH terms: Osteoarthritis; Tranexamic Acid

Study Results

Participant Flow

Arm/Group Title	Topical Tranexamic Acid	Intravenous Tranexamic Acid
Arm/Group Description	3 vials of tranexamic acid (1g tranexamic acid in 10cc each) must be mixed in the operating room by the team at the start of surgery with 45cc of saline solution (for a total of 3g tranexamic acid in 75mL solution). This solution will be applied to the open joint surfaces with two 60mL syringes (one with 60mL and one with 15m). The solution will be left in contact with the tissues for five minutes. The surgeon will suction away excess solution. The site may be irrigated before or after the tranexamic acid bath as long as the solution is in contact for at least five full minutes. Tourniquet will be released. Topical Tranexamic Acid: 3 vials of tranexamic acid (1g tranexamic acid in 10cc each) must be mixed in the operating room by the team at the start of surgery with 45cc of saline solution (for a total of 3g tranexamic acid in 75mL solution). This solution will be applied to the open joint surfaces with two 60mL syringes (one with 60mL and one with 15m).	1 vial (1g of IV tranexamic acid in 10mL solution) will be administered prior to inflation of the tourniquet. A second 1g dose of IV tranexamic acid will be given during initiation of the closure after the tourniquet is deflated and during closure. Intravenous Tranexamic Acid: 1 vial (1g of IV tranexamic acid in 10mL solution) will be administered prior to inflation of the tourniquet. A second 1g dose of IV tranexamic acid will be given during initiation of the closure after the tourniquet is deflated and during closure.
Period Title: Overall Study
STARTED	320	320
COMPLETED	320	320
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Topical Tranexamic Acid	Intravenous Tranexamic Acid	Total
Arm/Group Description	3 vials of tranexamic acid (1g tranexamic acid in 10cc each) must be mixed in the operating room by the team at the start of surgery with 45cc of saline solution (for a total of 3g tranexamic acid in 75mL solution). This solution will be applied to the open joint surfaces with two 60mL syringes (one with 60mL and one with 15m). Topical Tranexamic Acid: 3 vials of tranexamic acid (1g tranexamic acid in 10cc each) must be mixed in the operating room by the team at the start of surgery with 45cc of saline solution (for a total of 3g tranexamic acid in 75mL solution). This solution will be applied to the open joint surfaces with two 60mL syringes (one with 60mL and one with 15m). The solution will be left in contact with the tissues for five minutes.	1 vial (1g of IV tranexamic acid in 10mL solution) will be administered prior to inflation of the tourniquet. A second 1g dose of IV tranexamic acid will be given during initiation of the closure after the tourniquet is deflated and during closure. Intravenous Tranexamic Acid: 1 vial (1g of IV tranexamic acid in 10mL solution) will be administered prior to inflation of the tourniquet. A second 1g dose of IV tranexamic acid will be given during initiation of the closure after the tourniquet is deflated and during closure.	Total of all reporting groups
Overall Participants	320	320	640
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	146 45.6%	151 47.2%	297 46.4%
>=65 years	174 54.4%	169 52.8%	343 53.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.87 (9.42)	66.35 (9.16)	66.6 (9.28)
Sex: Female, Male (Count of Participants)
Female	193 60.3%	187 58.4%	380 59.4%
Male	127 39.7%	133 41.6%	260 40.6%

Outcome Measures

1. Primary Outcome

Title	Total Blood Loss
Description	The amount of blood lost during surgery is the primary outcome measure. Blood loss is determineusing an equation that calculates the patient's blood volume based on their height and weight, then multiplies the patient's blood volume by the change in their hematocrit after surgery compared to before surgery.
Time Frame	during surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topical Tranexamic Acid	Intravenous Tranexamic Acid
Arm/Group Description	3 vials of tranexamic acid (1g tranexamic acid in 10cc each) must be mixed in the operating room by the team at the start of surgery with 45cc of saline solution (for a total of 3g tranexamic acid in 75mL solution). This solution will be applied to the open joint surfaces with two 60mL syringes (one with 60mL and one with 15m). Topical Tranexamic Acid: 3 vials of tranexamic acid (1g tranexamic acid in 10cc each) must be mixed in the operating room by the team at the start of surgery with 45cc of saline solution (for a total of 3g tranexamic acid in 75mL solution). This solution will be applied to the open joint surfaces with two 60mL syringes (one with 60mL and one with 15m). The solution will be left in contact with the tissues for five minutes.	1 vial (1g of IV tranexamic acid in 10mL solution) will be administered prior to inflation of the tourniquet. A second 1g dose of IV tranexamic acid will be given during initiation of the closure after the tourniquet is deflated and during closure. Intravenous Tranexamic Acid: 1 vial (1g of IV tranexamic acid in 10mL solution) will be administered prior to inflation of the tourniquet. A second 1g dose of IV tranexamic acid will be given during initiation of the closure after the tourniquet is deflated and during closure.
Measure Participants	320	320
Mean (Standard Deviation) [ml]	323.59 (255.89)	271.22 (212.06)

2. Secondary Outcome

Title	Drain Output
Description	The amount of blood collected by a drain attached to the knee is measured 24 hours after surgery.
Time Frame	from end of surgery to 24 hours postoperatively

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topical Tranexamic Acid	Intravenous Tranexamic Acid
Arm/Group Description	3 vials of tranexamic acid (1g tranexamic acid in 10cc each) must be mixed in the operating room by the team at the start of surgery with 45cc of saline solution (for a total of 3g tranexamic acid in 75mL solution). This solution will be applied to the open joint surfaces with two 60mL syringes (one with 60mL and one with 15m). Topical Tranexamic Acid: 3 vials of tranexamic acid (1g tranexamic acid in 10cc each) must be mixed in the operating room by the team at the start of surgery with 45cc of saline solution (for a total of 3g tranexamic acid in 75mL solution). This solution will be applied to the open joint surfaces with two 60mL syringes (one with 60mL and one with 15m). The solution will be left in contact with the tissues for five minutes.	1 vial (1g of IV tranexamic acid in 10mL solution) will be administered prior to inflation of the tourniquet. A second 1g dose of IV tranexamic acid will be given during initiation of the closure after the tourniquet is deflated and during closure. Intravenous Tranexamic Acid: 1 vial (1g of IV tranexamic acid in 10mL solution) will be administered prior to inflation of the tourniquet. A second 1g dose of IV tranexamic acid will be given during initiation of the closure after the tourniquet is deflated and during closure.
Measure Participants	320	320
Mean (Standard Deviation) [ml]	560.13 (297.21)	456.22 (275.39)

3. Secondary Outcome

Title	The Number Patients Requiring a Transfusion
Description	TThe number Patients requiring a transfusion over the course of the patient's hospital stay.
Time Frame	over course of hospital stay (averaging three days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV TXA Group	Topical TXA Group
Arm/Group Description	Kaitlin - Explain this group....	Kaitlin - Explain this group
Measure Participants	320	320
Count of Participants [Participants]	2 0.6%	6 1.9%

Adverse Events

Time Frame	During the hospital stay, adverse event data was collected
Arm/Group Title	Topical Tranexamic Acid		Intravenous Tranexamic Acid
Arm/Group Description	3 vials of tranexamic acid (1g tranexamic acid in 10cc each) must be mixed in the operating room by the team at the start of surgery with 45cc of saline solution (for a total of 3g tranexamic acid in 75mL solution). This solution will be applied to the open joint surfaces with two 60mL syringes (one with 60mL and one with 15m). Topical Tranexamic Acid: 3 vials of tranexamic acid (1g tranexamic acid in 10cc each) must be mixed in the operating room by the team at the start of surgery with 45cc of saline solution (for a total of 3g tranexamic acid in 75mL solution). This solution will be applied to the open joint surfaces with two 60mL syringes (one with 60mL and one with 15m). The solution will be left in contact with the tissues for five minutes.		1 vial (1g of IV tranexamic acid in 10mL solution) will be administered prior to inflation of the tourniquet. A second 1g dose of IV tranexamic acid will be given during initiation of the closure after the tourniquet is deflated and during closure. Intravenous Tranexamic Acid: 1 vial (1g of IV tranexamic acid in 10mL solution) will be administered prior to inflation of the tourniquet. A second 1g dose of IV tranexamic acid will be given during initiation of the closure after the tourniquet is deflated and during closure.
All Cause Mortality
	Topical Tranexamic Acid		Intravenous Tranexamic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Topical Tranexamic Acid		Intravenous Tranexamic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/320 (0%)		0/320 (0%)
Other (Not Including Serious) Adverse Events
	Topical Tranexamic Acid		Intravenous Tranexamic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/320 (0%)		0/320 (0%)

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.