Trial Outcomes & Findings for Efficacy of Low-dose Intra-articular Tranexamic Acid in Total Knee Replacement (NCT NCT01850394)

Results Overview

* Drainage blood loss measured by accumulating total drainage volume postoperatively * Calculated total blood loss measured by using specific formula and difference between hematocrit preoperatively and the fourth postoperative day

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

152 participants

Primary outcome timeframe

5 days after surgery

Results posted on

2013-12-13

Participant Flow

The patients, who planned to undergo primary total knee replacement, were recruited from medical clinics before setting the operative schedule between 2009 and 2010.

Seventeen patients were excluded that including refusal to participate (4 patients), serum creatinine more than 2.0 mg% (4 patients), rheumatoid arthritis (4 patients), abnormal coagulogram (3 patients), and history of stroke (2 patients)

Participant milestones

Participant milestones
Measure	Control Group physiologic saline 25 ml Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group	TXA-250 Group A total of 25-ml solution with 250-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure	TXA-500 Group A total of 25-ml solution with 500-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure
Overall Study STARTED	45	45	45
Overall Study COMPLETED	45	45	45
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy of Low-dose Intra-articular Tranexamic Acid in Total Knee Replacement

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Control Group n=45 Participants physiologic saline 25 ml Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group	TXA-250 Group n=45 Participants A total of 25-ml solution with 250-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure	TXA-500 Group n=45 Participants A total of 25-ml solution with 500-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure	Total n=135 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants	20 Participants n=7 Participants	13 Participants n=5 Participants	53 Participants n=4 Participants
Age, Categorical >=65 years	25 Participants n=5 Participants	25 Participants n=7 Participants	32 Participants n=5 Participants	82 Participants n=4 Participants
Age Continuous	66.2 years STANDARD_DEVIATION 7.3 • n=5 Participants	67.6 years STANDARD_DEVIATION 8.7 • n=7 Participants	68.1 years STANDARD_DEVIATION 6.2 • n=5 Participants	67.3 years STANDARD_DEVIATION 7.5 • n=4 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	42 Participants n=7 Participants	40 Participants n=5 Participants	125 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	10 Participants n=4 Participants
Region of Enrollment Thailand	45 participants n=5 Participants	45 participants n=7 Participants	45 participants n=5 Participants	135 participants n=4 Participants

PRIMARY outcome

Timeframe: 5 days after surgery

Population: Using intention-to-treat analysis

* Drainage blood loss measured by accumulating total drainage volume postoperatively * Calculated total blood loss measured by using specific formula and difference between hematocrit preoperatively and the fourth postoperative day

Outcome measures

Outcome measures
Measure	Control Group n=45 Participants physiologic saline 25 ml Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group	TXA-250 Group n=45 Participants A total of 25-ml solution with 250-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure	TXA-500 Group n=45 Participants A total of 25-ml solution with 500-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure
Perioperative Blood Loss Calculated total blood loss	329.2 ml Standard Deviation 119.4	239.7 ml Standard Deviation 83.7	217.2 ml Standard Deviation 86.1
Perioperative Blood Loss Drainage blood loss	546.9 ml Standard Deviation 273.0	475.0 ml Standard Deviation 254.4	430.2 ml Standard Deviation 224.0

PRIMARY outcome

Timeframe: 5 days after surgery

Population: Use intention-to-treat analysis

Total hemoglobin loos measured by difference between hemoglobin preoperatively and the fourth postoperative day

Outcome measures

Outcome measures
Measure	Control Group n=45 Participants physiologic saline 25 ml Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group	TXA-250 Group n=45 Participants A total of 25-ml solution with 250-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure	TXA-500 Group n=45 Participants A total of 25-ml solution with 500-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure
Total Hemoglobin Loss	2.9 g/dL Standard Deviation 1.2	2.2 g/dL Standard Deviation 0.7	2.2 g/dL Standard Deviation 0.7

SECONDARY outcome

Timeframe: 1 year after surgery

Population: Using intention-to-treat analysis

Knee function score was measured with 2 methods, and were evaluated preoperatively and then postoperatively at 3-month, 6-month, and 1-year period. 1. Knee Society Knee Score using for rating knee function measurement and subdivided into two parts; knee score and function score 1.1. Knee score : calculated from pain, presence of deformity, total range of flexion, alignment, and stability. Total score is 100 (0-100), more score means better. 1.2. Function score : calculated from patient's ability to walk and climb stairs. The score ranges from 0-100, more score means better. 2. Western Ontario and McMaster Universities Arthritis Index or WOMAC score : a widely used, standardized questionnaires for evaluating the condition of patients with knee osteoarthritis, including pain (score = 0-20), stiffness (0-8), and functional limitation (0-68). Total score ranges from 0-68, lower score means better.

Outcome measures

Outcome measures
Measure	Control Group n=45 Participants physiologic saline 25 ml Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group	TXA-250 Group n=45 Participants A total of 25-ml solution with 250-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure	TXA-500 Group n=45 Participants A total of 25-ml solution with 500-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure
Knee Function Scores WOMAC score at 1 year	15.5 units on a scale Standard Deviation 6.6	15.1 units on a scale Standard Deviation 6.2	14.5 units on a scale Standard Deviation 7.1
Knee Function Scores Knee Society Knee score at 1 year	148.9 units on a scale Standard Deviation 10.1	151.2 units on a scale Standard Deviation 9.1	150.9 units on a scale Standard Deviation 9.3

SECONDARY outcome

Timeframe: postoperative period (5 days after surgery)

Outcome measures

Outcome measures
Measure	Control Group n=45 Participants physiologic saline 25 ml Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group	TXA-250 Group n=45 Participants A total of 25-ml solution with 250-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure	TXA-500 Group n=45 Participants A total of 25-ml solution with 500-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure
Number of Patients Required Blood Transfusion	10 participants	6 participants	0 participants

SECONDARY outcome

Timeframe: postoperative 1-year period

Population: Using Intention-to-treat analysis

Postoperative complications were measured as an incidence of the following complications; * wound hematoma * surgical site infection * systemic infection * deep vein thrombosis * pulmonary embolism * knee stiffness requiring manipulation * medical complication such as myocardial infarction, congestive hear failure

Outcome measures

Outcome measures
Measure	Control Group n=45 Participants physiologic saline 25 ml Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group	TXA-250 Group n=45 Participants A total of 25-ml solution with 250-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure	TXA-500 Group n=45 Participants A total of 25-ml solution with 500-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure
Number of Patients Having Postoperative Complications Re-dressing incidence	3 participants	0 participants	0 participants
Number of Patients Having Postoperative Complications Re-clamp incidence	6 participants	1 participants	0 participants
Number of Patients Having Postoperative Complications Venous thromboembolic complication	4 participants	1 participants	2 participants
Number of Patients Having Postoperative Complications Congestive heart failure	0 participants	1 participants	0 participants

Adverse Events

Control Group

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

TXA-250 Group

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

TXA-500 Group

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Control Group n=45 participants at risk physiologic saline 25 ml Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group	TXA-250 Group n=45 participants at risk A total of 25-ml solution with 250-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure	TXA-500 Group n=45 participants at risk A total of 25-ml solution with 500-mg tranexamic acid Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure
Blood and lymphatic system disorders Venous thromboembolic complication	8.9% 4/45 • Number of events 4 • 5 days Perioperative venous thromboembolic complications * deep vein thrombosis screened with duplex doppler ultrasound in all cases * pulmonary embolism diagnosed with clinical hypoxemia and confirmed with computer tomography angiogram	2.2% 1/45 • Number of events 1 • 5 days Perioperative venous thromboembolic complications * deep vein thrombosis screened with duplex doppler ultrasound in all cases * pulmonary embolism diagnosed with clinical hypoxemia and confirmed with computer tomography angiogram	4.4% 2/45 • Number of events 2 • 5 days Perioperative venous thromboembolic complications * deep vein thrombosis screened with duplex doppler ultrasound in all cases * pulmonary embolism diagnosed with clinical hypoxemia and confirmed with computer tomography angiogram

Other adverse events

Adverse event data not reported

Additional Information

Dr. Paphon Sa-ngasoongsong

Faculty of Medicine, Ramathibodi Hospital, Mahidol University

Phone: 66-2-2011589

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place