Trial Outcomes & Findings for Tranexamic Acid in Knee Joint Surgery (NCT NCT02278263)
NCT ID: NCT02278263
Last Updated: 2020-05-20
Results Overview
The loss of haemoglobin (Hb) was then estimated according to the formula: Hb(loss) = Blood volume (BV) x (Hbi-Hbe) x 0.001+Hbt where Hb (loss) (g) is the amount of Hb lost, Hbi (g/L) the Hb concentration before surgery, Hbe (g/L) is the Hbe concentration on the third day after surgery, and Hbt (g) is the total amount of allogeneic Hb transfused. A unit of banked blood is considered to contain a minimum of 40g Hb (Blood component data sheet, New Zealand Blood Services \[NZBS\]). All units of blood are processed and stored in a nationally standardised manner. The blood loss (ml) was related to the patient's preoperative Hb value (g/L): Blood loss =1000 x Hb(loss) /Hbi
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
150 participants
Primary outcome timeframe
Post operative day 3
Results posted on
2020-05-20
Participant Flow
The hospital databases will be searched for eligible patients on the waiting list for unilateral total knee joint replacement. Patients will be approached in the preadmission clinics and then consented on the day of surgery. Recruitment period is to be over 2 years or sooner once we have recruited the final patient (n=150)
Patients were excluded after consenting to participate, if they failed to receive spinal anaesthesia.
Participant milestones
| Measure |
Control
Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Intraarticular
Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Tranexamic Acid: Given intraarticularly
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Systemic
Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet
Tranexamic Acid: Given intravenously
Normal saline (0.9% NaCl): Administered in all 3 groups
|
|---|---|---|---|
|
Overall Study
STARTED
|
30
|
60
|
60
|
|
Overall Study
COMPLETED
|
23
|
60
|
51
|
|
Overall Study
NOT COMPLETED
|
7
|
0
|
9
|
Reasons for withdrawal
| Measure |
Control
Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Intraarticular
Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Tranexamic Acid: Given intraarticularly
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Systemic
Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet
Tranexamic Acid: Given intravenously
Normal saline (0.9% NaCl): Administered in all 3 groups
|
|---|---|---|---|
|
Overall Study
Protocol Violation
|
7
|
0
|
9
|
Baseline Characteristics
Tranexamic Acid in Knee Joint Surgery
Baseline characteristics by cohort
| Measure |
Control
n=23 Participants
Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Intraarticular
n=60 Participants
Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Tranexamic Acid: Given intraarticularly
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Systemic
n=51 Participants
Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet
Tranexamic Acid: Given intravenously
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Total
n=134 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
|
6 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
17 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
102 Participants
n=4 Participants
|
|
Age, Continuous
|
69.67 years
STANDARD_DEVIATION 7.75 • n=5 Participants
|
69.72 years
STANDARD_DEVIATION 8.85 • n=7 Participants
|
70.79 years
STANDARD_DEVIATION 8.61 • n=5 Participants
|
70.12 years
STANDARD_DEVIATION 8.53 • n=4 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
75 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
59 Participants
n=4 Participants
|
|
Region of Enrollment
New Zealand
|
23 participants
n=5 Participants
|
60 participants
n=7 Participants
|
51 participants
n=5 Participants
|
134 participants
n=4 Participants
|
|
Preoperative Hb
|
134 grams/L
STANDARD_DEVIATION 11.8 • n=5 Participants
|
138 grams/L
STANDARD_DEVIATION 12.2 • n=7 Participants
|
138 grams/L
STANDARD_DEVIATION 10.6 • n=5 Participants
|
137 grams/L
STANDARD_DEVIATION 11.5 • n=4 Participants
|
|
Body Mass Index
|
32.3 kg/m^2
STANDARD_DEVIATION 6.6 • n=5 Participants
|
31.2 kg/m^2
STANDARD_DEVIATION 5.5 • n=7 Participants
|
31.2 kg/m^2
STANDARD_DEVIATION 5.5 • n=5 Participants
|
31.3 kg/m^2
STANDARD_DEVIATION 5.7 • n=4 Participants
|
|
Preop Hb (number of days prior to surgery date)
|
28 days
STANDARD_DEVIATION 34 • n=5 Participants
|
39 days
STANDARD_DEVIATION 40 • n=7 Participants
|
28 days
STANDARD_DEVIATION 34 • n=5 Participants
|
31 days
STANDARD_DEVIATION 33 • n=4 Participants
|
PRIMARY outcome
Timeframe: Post operative day 3Population: The number provided here for each group are those patients analyzed after patients had been excluded due to breaches in the study protocol. As stated in the power calculation for this primary outcome, an attrition rate of 15% (ie breaches in study protocol, drop out etc) had been accounted for. Hence the discrepancy.
The loss of haemoglobin (Hb) was then estimated according to the formula: Hb(loss) = Blood volume (BV) x (Hbi-Hbe) x 0.001+Hbt where Hb (loss) (g) is the amount of Hb lost, Hbi (g/L) the Hb concentration before surgery, Hbe (g/L) is the Hbe concentration on the third day after surgery, and Hbt (g) is the total amount of allogeneic Hb transfused. A unit of banked blood is considered to contain a minimum of 40g Hb (Blood component data sheet, New Zealand Blood Services \[NZBS\]). All units of blood are processed and stored in a nationally standardised manner. The blood loss (ml) was related to the patient's preoperative Hb value (g/L): Blood loss =1000 x Hb(loss) /Hbi
Outcome measures
| Measure |
Control
n=23 Participants
Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Intraarticular
n=60 Participants
Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Tranexamic Acid: Given intraarticularly
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Systemic
n=51 Participants
Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet
Tranexamic Acid: Given intravenously
Normal saline (0.9% NaCl): Administered in all 3 groups
|
|---|---|---|---|
|
Blood Loss
|
1090 mls
Standard Deviation 589
|
716 mls
Standard Deviation 377
|
746 mls
Standard Deviation 321
|
SECONDARY outcome
Timeframe: Postoperatively within 30 days after surgeryPopulation: Logistic regression for categorical/binary outcomes
Rates of deep vein thrombosis (DVT) and pulmonary embolus (PE) in each group recorded as a percentage
Outcome measures
| Measure |
Control
n=23 Participants
Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Intraarticular
n=60 Participants
Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Tranexamic Acid: Given intraarticularly
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Systemic
n=51 Participants
Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet
Tranexamic Acid: Given intravenously
Normal saline (0.9% NaCl): Administered in all 3 groups
|
|---|---|---|---|
|
Number of Participants Experiencing Symptomatic Venothromboembolic (VTE) Disease
DVT
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Experiencing Symptomatic Venothromboembolic (VTE) Disease
PE
|
0 Participants
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Participants will be followed for the duration of their hospital stay expected to be an average of 3-5 daysPopulation: Logistic regression for binary outcomes
Those patients receiving blood products. Standardised protocol is as follows: The criterion for transfusion of blood products will be a haemoglobin \< 80g/L or a haemoglobin \<100g/L in a patient with ischaemic heart disease or with significant symptomatology
Outcome measures
| Measure |
Control
n=23 Participants
Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Intraarticular
n=60 Participants
Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Tranexamic Acid: Given intraarticularly
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Systemic
n=51 Participants
Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet
Tranexamic Acid: Given intravenously
Normal saline (0.9% NaCl): Administered in all 3 groups
|
|---|---|---|---|
|
Number of Participants Receiving Allogenic Blood Transfusion
|
2 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Average length of stay is expected to be 3 to 5 daysDay of surgery is counted as Day 0.
Outcome measures
| Measure |
Control
n=23 Participants
Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Intraarticular
n=60 Participants
Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Tranexamic Acid: Given intraarticularly
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Systemic
n=51 Participants
Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet
Tranexamic Acid: Given intravenously
Normal saline (0.9% NaCl): Administered in all 3 groups
|
|---|---|---|---|
|
Length of Stay (LOS)
|
4 days
Interval 3.0 to 5.0
|
4 days
Interval 3.0 to 4.0
|
4 days
Interval 3.0 to 5.0
|
SECONDARY outcome
Timeframe: Days 1-3Population: Range of passive flexion measured and the data presented here are the averages with standard deviations
Range of motion measured in degrees for postoperative days 1 to 3
Outcome measures
| Measure |
Control
n=23 Participants
Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Intraarticular
n=60 Participants
Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Tranexamic Acid: Given intraarticularly
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Systemic
n=51 Participants
Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet
Tranexamic Acid: Given intravenously
Normal saline (0.9% NaCl): Administered in all 3 groups
|
|---|---|---|---|
|
Range of Passive Flexion
Day 1
|
65 degrees
Standard Deviation 28
|
74 degrees
Standard Deviation 15
|
68 degrees
Standard Deviation 15
|
|
Range of Passive Flexion
Day 2
|
76 degrees
Standard Deviation 15
|
81 degrees
Standard Deviation 13
|
80 degrees
Standard Deviation 13
|
|
Range of Passive Flexion
Day 3
|
82 degrees
Standard Deviation 13
|
87 degrees
Standard Deviation 11
|
87 degrees
Standard Deviation 13
|
SECONDARY outcome
Timeframe: Days 1-3Population: Range of active flexion measured and the data presented here represent the average active flexion with SD.
Range of motion measured in degrees on postoperative days 1-3
Outcome measures
| Measure |
Control
n=23 Participants
Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Intraarticular
n=60 Participants
Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Tranexamic Acid: Given intraarticularly
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Systemic
n=51 Participants
Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet
Tranexamic Acid: Given intravenously
Normal saline (0.9% NaCl): Administered in all 3 groups
|
|---|---|---|---|
|
Range of Active Flexion
Day 1
|
57 degrees
Standard Deviation 23
|
65 degrees
Standard Deviation 18
|
58 degrees
Standard Deviation 16
|
|
Range of Active Flexion
Day 2
|
71 degrees
Standard Deviation 15
|
75 degrees
Standard Deviation 14
|
72 degrees
Standard Deviation 16
|
|
Range of Active Flexion
Day 3
|
75 degrees
Standard Deviation 11
|
82 degrees
Standard Deviation 12
|
78 degrees
Standard Deviation 16
|
SECONDARY outcome
Timeframe: Day 1Intravenous fluid (excluding blood transfusion) given during and first 24 hours after surgery
Outcome measures
| Measure |
Control
n=23 Participants
Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Intraarticular
n=60 Participants
Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Tranexamic Acid: Given intraarticularly
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Systemic
n=51 Participants
Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet
Tranexamic Acid: Given intravenously
Normal saline (0.9% NaCl): Administered in all 3 groups
|
|---|---|---|---|
|
Perioperative Fluid Administration
|
1765 mls
Interval 1320.0 to 2209.0
|
1613 mls
Interval 1455.0 to 1770.0
|
1807 mls
Interval 1581.0 to 2033.0
|
Adverse Events
Control
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Intraarticular
Serious events: 2 serious events
Other events: 4 other events
Deaths: 0 deaths
Systemic
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Control
n=23 participants at risk
Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Intraarticular
n=60 participants at risk
Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Tranexamic Acid: Given intraarticularly
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Systemic
n=51 participants at risk
Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet
Tranexamic Acid: Given intravenously
Normal saline (0.9% NaCl): Administered in all 3 groups
|
|---|---|---|---|
|
Vascular disorders
Infection
|
0.00%
0/23 • 30 days
The total number at risk is now consistent with the numbers provided in the participant flow module. This also applies to the 'Other adverse events' data table.
|
3.3%
2/60 • Number of events 2 • 30 days
The total number at risk is now consistent with the numbers provided in the participant flow module. This also applies to the 'Other adverse events' data table.
|
2.0%
1/51 • Number of events 1 • 30 days
The total number at risk is now consistent with the numbers provided in the participant flow module. This also applies to the 'Other adverse events' data table.
|
Other adverse events
| Measure |
Control
n=23 participants at risk
Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Intraarticular
n=60 participants at risk
Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Tranexamic Acid: Given intraarticularly
Normal saline (0.9% NaCl): Administered in all 3 groups
|
Systemic
n=51 participants at risk
Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet
Tranexamic Acid: Given intravenously
Normal saline (0.9% NaCl): Administered in all 3 groups
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Blood transfusion
|
13.0%
3/23 • 30 days
The total number at risk is now consistent with the numbers provided in the participant flow module. This also applies to the 'Other adverse events' data table.
|
6.7%
4/60 • 30 days
The total number at risk is now consistent with the numbers provided in the participant flow module. This also applies to the 'Other adverse events' data table.
|
9.8%
5/51 • 30 days
The total number at risk is now consistent with the numbers provided in the participant flow module. This also applies to the 'Other adverse events' data table.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place