Clinical trial NCT02684851
Conditions: Acetabular Fractures
Sponsor: Wake Forest University Health Sciences
Start date: 2012-10-01; Completion date: 2017-07-25
Enrollment: 87 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine if patients undergoing acetabular ORIF (open reduction with internal fixation) who receive tranexamic acid have a reduced risk of allogenic blood transfusion, perioperative blood loss, wound complication and higher risk for thromboembolic events compared to patients who receive placebo. Investigators want to determine the cost-effectiveness related to allogenic blood transfusion as a blood loss management strategy in acetabular open reduction internal fixation (ORIF). Orthopaedic surgery carries with it a significant risk for blood loss. Current management of perioperative blood loss is the use of allogenic blood transfusion. Allogenic blood transfusion carries with it a risk for HIV and Hepatitis C as well as multiple adverse reactions. There have been significant efforts to reduce the use of allogenic blood transfusion in orthopaedic surgery. Tranexamic acid, an anti-fibrinolytic agent, has been used in management of blood during surgery. In order to determine the impact of tranexamic acid in reducing blood loss among patients undergoing acetabular ORIF, investigators will conduct a prospective randomized study. Patients undergoing acetabular surgery will be screened for this study. Patients will be then randomized to placebo or tranexamic acid which will be administered during and after surgery. The following data will be collected: patient characteristics, surgery information, blood loss, blood transfusions, wound complication within 30 days of surgery, and cost.

Detailed description:
In this study, investigators plan to prospectively determine the effect of tranexamic acid on blood loss and outcome after surgery to the acetabulum.

Patients will be randomized into two groups. In this study, investigators plan to administer a 10mg/kg dose within 30 minutes of surgery followed by a 10mg/kg infusion over a 4hr period to the treatment group (for patients weighting over 100kg, a weight of 100kg will be used for the dose calculation). The control group will receive equal volumes of and rates of normal saline.

Research Questions:

1. Do patients undergoing acetabular ORIF who receive tranexamic acid have a reduced risk of allogenic blood transfusion as compared to patients who receive placebo?
2. Do patients undergoing acetabular ORIF who receive tranexamic acid have reduced peri-operative blood loss as compared to patients who receive placebo?
3. Do patients undergoing acetabular ORIF who receive tranexamic acid have a higher risk for thromboembolic events than patients who receive placebo?
4. Do patients undergoing acetabular ORIF who receive tranexamic acid have a reduced risk of wound complications (prolonged wound drainage, return to the OR within 30 days, infection)?
5. Is the use of tranexamic acid cost effective relative to the use of allogenic blood transfusion as a blood loss management strategy in acetabular ORIF?

Arms: arm 1: Inactive arm 2: Tranexamic acid: anti-fibrinolytic agents
Interventions: intervention 1: Tranexamic Acid intervention 2: Placebo
Intervention descriptions: intervention 1: Tranexamic acid: anti-fibrinolytic agents intervention 2: Placebo

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
The Use of Tranexamic Acid to Reduce Blood Loss in Acetabular Surgery 
 
 
 
 
 
 
 
Primary Investigator:  
Madhav Karunakar, MD 
 
 
Co-Investigator: 
William Lack, MD 
Michael Bosse, MD 
Stephen Sims, MD 
James Kellam, MD 
Rachel Seymour, PhD 
Matthew Wilson, MD 
Joseph Hsu, MD 
 
Protocol Version:3 
Protocol Date: 4/15/2013 


 
 
Background and Significance: 
 
 
Orthopaedic surgery carries with it a significant risk for blood loss.  Historically, 
this blood loss has been managed with allogenic blood transfusion when necessary.  
However, in recent years there has been a strong push to reduce the use of allogenic 
blood.[6, 9,24,34]  Even in developed countries, the demand for allogenic blood 
frequently exceeds the supply, and although multiple safety measures are in place to 
prevent “wrong blood” transfusions, the incidence of clerical errors is still unacceptably 
high, ranging from 1/15,000-1/20,000.[23]  Allogenic blood carries with it a risk for HIV 
and Hepatis C, as well as multiple adverse reactions.[23]  Furthermore, allogenic blood 
transfusion is known to have significant immunomodulatory effects, and the results of 
three extensive studies, involving more than 22,000 orthopaedic patients, showed that 
allogenic blood transfusion significantly increases the risk of postoperative infection.[5, 
7, 29]  Thus, significant effort has been expended toward reducing allogenic blood 
transfusion in orthopaedic surgery. 
Multiple anti-fibrinolytic agents have been used for this purpose, including 
tranexamic acid (TXA), aprotinin, and epsilon-aminocaproic acid (EACA).  Of these 
three, TXA has been the most widely used in recent orthopaedic studies.[21]  Reasons for 
this include the fact that aprotinin has a higher mortality rate than either TXA or 
EACA.[12]  Furthermore, TXA is the cheapest of the three and has excellent penetration 
of the major joints.[35]  Thus, we feel that TXA is the most appropriate anti-fibrinolytic 
for further study. 
 
  
 
Specific Research Questions: 
1. Do patients undergoing acetabular ORIF who receive tranexamic acid have a 
reduced risk of allogenic blood transfusion as compared to patients who receive 
placebo? 
2. Do patients undergoing acetabular ORIF who receive tranexamic acid have 
reduced peri-operative blood loss as compared to patients who receive placebo?  
3. Do patients undergoing acetabular ORIF who receive tranexamic acid have a 
higher risk for thromboembolic events than patients who receive placebo? 
4. Do patients undergoing acetabular ORIF who receive tranexamic acid have a 
reduced risk of wound complications (prolonged wound drainage, return to the 
OR within 30 days, infection)? 
5. Is the use of tranexamic acid cost effective relative to the use of allogenic blood 
transfusion as a blood loss management strategy in acetabular ORIF?     
 
 
 
 
 
 


1. Do patients undergoing acetabular ORIF who receive tranexamic acid have a 
reduced risk of allogenic blood transfusion as compared to patients who receive 
placebo? 
 
The ability of TXA to reduce the use of allogenic blood transfusion relative to placebo 
is unclear.  The largest ever study on the use of TXA was conducted in general trauma 
patients, and included 10,096 patients randomized to receive TXA, and 10,115 
randomized to receive placebo with an equivalent dose of normal saline.[33]  This study 
showed no significant difference in the incidence of blood transfusion between groups 
(relative risk of transfusion with TXA of 0.98, 95% CI 0.96-1.01).   
Multiple studies have attempted to answer this question specifically in joint 
arthroplasty patients and the results have been mixed.  Several studies in total joint 
arthroplasty found no benefit of TXA relative to a saline placebo.[4,13,14,27]  In 
contrast, at least 5 other prospective studies of joint arthroplasty patients have shown at 
least a mild reduction in the risk of transfusion with use of TXA in total joint 
arthroplasty.[2,8,11,18,26]  A metanalysis of these studies in total joint patients showed a 
transfusion benefit of TXA relative to placebo, with a risk difference of -.20 (-0.20, 95% 
CI -0.29 to -0.11).[35]  These results were consistent with two other meta-analyses, 
which included orthopaedic patients from all of the sub-specialties, and estimated that use 
of TXA reduced the incidence of blood transfusion by up to 50%.[21,39]  However, the 
authors noted that none of the prior studies in orthopaedics have ever included more than 
150 patients, and called for a large prospective randomized trial in order to clarify the 
differences in reported literature.[14,21,35,39]  
In this study, we plan to prospectively record the overall incidence of allogenic 
blood transfusions.  In addition, we will record the total number and volume of allogenic 
blood products required by each patient.  We do not plan to use erythropoietin in any of 
our patients.  This study will not have a specific “transfusion trigger.”  Previous studies 
have advocated for blood transfusions to be based on an overall assessment of the 
patient’s physiologic status, and not an arbitrary “transfusion trigger.”[6,9,34] We agree 
that you should treat the patient and not a number, and thus the decision to transfuse will 
be left up to the individual treating surgeon.  While the decision to transfuse will thus be 
subjective, and could possibly differ between surgeons, the fact that our study is double 
blinded and randomized should account for this potential source of bias.  Overall, we 
hypothesize that our study will demonstrate a reduction in the incidence of allogenic 
blood transfusion in patients that receive TXA, regardless of dosing, as compared to 
patients who receive a saline placebo.    
 
 
2. Do patients undergoing acetabular ORIF who receive tranexamic acid have 
reduced perioperative blood loss as compared to patients who receive placebo?  
 
There have been at least three meta-analyses of prospective randomized trials in 
orthopaedics which attempted to answer this question, and each meta-analysis has 
consistently shown reduced perioperative blood loss with the use of TXA relative to 
placebo.[21,35,39]  Specifically in total joint arthroplasty, patients who received TXA 
had a mean of 289 ml less peri-operative blood loss, as compared to patients who 


received a saline placebo.[35]  However, a separate meta-analysis isolated to total hip 
arthroplasty patients showed no benefit for TXA in terms of reduced blood loss.[14]  
Furthermore, the magnitude of reduction in peri-operative blood loss varied significantly 
between studies, and as reported above, the correlation between this result and with 
decreased risk of transfusion is not clear.  Two studies of this outcome in hip fracture 
patients found trends toward decreased transfusion risk.[32,40] 
In this study, we plan to report intra-operative blood loss based on the estimated 
blood loss (EBL) dictated into the procedure note at the time of surgery.  The EBL is an 
estimate based on the amount of blood remaining in sponges and drapes, as well as in 
suction containers at the end of the case.  Although this measurement has a subjective 
component, the fact that our study will be double blinded, and that patients will be 
randomized to the different treatment groups should reduce potential bias.   
In order to objectively quantify peri-operative blood loss, we will report total peri-
operative blood loss based on the formula derived by Gross,[16] where peri-operative 
blood loss = estimated blood volume × (haematocrit reduction/mean haematocrit), and 
blood volume is estimated with the formula: Blood volume (BV) (ml) = 70 × weight 
(kg).[25]  Since these calculations will be based on objective laboratory values, this 
should further help to control for any potential bias introduced by the subjective nature of 
the EBL measurement.  Overall, we hypothesize that TXA will be reduce peri-operative 
blood loss relative to placebo.      
 
 
 
3. Do patients undergoing acetabular ORIF who receive tranexamic acid have a 
higher risk for thromboembolic events than patients who receive placebo? 
 
This is a key question that has not been answered by prior studies of TXA in 
orthopaedics.  TXA is a lysine analogue that functions by inhibiting the conversion of 
plasminogen to its active form plasmin.  Since plasmin is responsible for the breakdown 
of fibrin in clots, TXA’s mechanism is presumably one of decreased clot breakdown.   
Theoretically, TXA could thus place the patient at increased risk for thromboembolic 
events.  However, previous studies have shown that TXA exerts its effects mostly in the 
wound bed,[3] and that it has no effect on fibrinolytic activity in the wall of the veins.[1]  
Therefore, the effect of TXA on thromboembolic events should be minimal.   
This presumption is borne out by the fact that none of the previous meta-analyses 
on this topic in orthopaedics has ever demonstrated a significantly increased risk of 
thromboembolism following the use of TXA.[14,21,35,39]  However, only two studies 
have been performed in orthopaedic trauma and these studied hip fracture patients. 
[32,40] Additionally, no prospective clinical trial of TXA in orthopaedics has ever 
included more than 150 patients, and the meta-analyses were markedly underpowered to 
detect clinically significant differences in the incidence of DVT.   
Patients will be treated in standard fashion with mechanical and anticoagulant 
prophylaxis against VTE as appropriate based on the clinical scenario. Symptomatic 
venous thromboembolism will be diagnosed by history, exam, and standard tests. We will 
not screen for asymptomatic DVT. The American Academy of Orthopaedic Surgeons 
guidelines on DVT prophylaxis recommend against screening asymptomatic patients 


with Doppler ultrasound and there are significant questions regarding the correlation 
between DVT and more significant outcomes such as PE. Although our study will not be 
specifically powered for other thromboembolic outcomes, we will also prospectively 
record the incidence symptomatic thromboembolic events such as pulmonary embolism, 
stroke, and myocardial infarction.  We hypothesize that there will be no increased risk of 
thromboembolic events in patients receiving TXA, regardless of dosing, as compared to 
patients receiving placebo. 
 
4. Do patients undergoing acetabular ORIF who receive tranexamic acid have a 
reduced risk of wound complications (prolonged wound drainage, return to the 
OR within 30 days, infection)? 
 
This is an important question as decreasing blood loss may reduce transfusion risk as well 
as risk of drainage and hematoma formation, with the potential to decrease risk of 
infection. This has not yet been shown to be true in orthopaedics, let alone orthopaedic 
trauma surgery. The incidence of infection with acetabular ORIF has been reported to be 
2 to 5% in general populations and up to 15% in morbidly obese patients and showing a 
decreased infection rate with tranexamic acid would be a very important finding. 
Infection and associated outcomes including wound drainage and return to the OR for 
drainage and hematoma evacuation can be recorded to study the affects of tranexamic 
acid on wound healing.  
 
 
5. Is the use of tranexamic acid cost effective relative to the use of allogenic blood 
transfusion as a blood loss management strategy in acetabular ORIF?     
 
A few small previous studies have shown TXA to be cost effective relative to a 
placebo in orthopaedic patients.[20,26,28]  However, the majority of trials have not 
reported on cost-effectiveness, and meta-analyses on this topic have not been able to 
draw definitive conclusions on this issue.[8,13,15,19,21,27,35,39]  Neither of the two 
studies in orthopaedic trauma, specifically hip fracture patients, reported on this. [32,40] 
In this study, we will calculate the cost of tranexamic acid administration in each 
treatment group, and compare this to the total cost of allogenic blood transfusion in each 
treatment group.  Since TXA is an inexpensive drug, we hypothesize that TXA will be a 
cost effective blood loss management strategy with acetabular ORIF.  
 
We plan to enroll 50 patients (N=25 treatment, N=25 controls) in a pilot study to test 
procedures and collect preliminary data.  While this pilot study will likely not have 
sufficient power to definitively address the specific aims and hypotheses, the preliminary 
data collected will provide information to plan future work.  
 
 
Study Design:  
 
Eligibility: 
 


Inclusion Criteria: All patients aged 18 or above undergoing acetabular ORIF.   
 
Exclusion Criteria:  
 
• 
All patients aged below 18 undergoing acetabulum surgery 
• 
Patients with color-blindness (color vision changes used to assess toxicity) 
• 
Patients with subarachnoid hemorrhage.  
• 
Patients with active intravascular coagualation.  
• 
Patients with a previous history of venous thromboembolism or with a history of 
hypercoaguable conditions (i.e. Factor V Leiden, antiphospholipid antibody).  
• 
Prisoners 
• 
Pregnant women 
 
Patient Consent:   
 
Orthopaedic surgery attendings and residents will identify potential study candidates 
during the initial consultation based on the presence of an acetabular fracture.  If the 
patient meets the inclusion and exclusion criteria (noted above), a member of the 
treatment team will discuss the study with eligible patients.  If the patient expresses 
interest in the study, the physician will notify the research staff.  Orthopaedic Clinical 
Research staff will describe study procedures in detail and go through the informed 
consent process to enroll the patient in the study.   The number of eligible patients, and 
the eventual number enrolled will be specifically reported. 
 
Dosing:   
 
Multiple different treatment regimens with TXA have been proposed, with doses ranging 
from as little as 10mg/kg in a single dose, up to a total of 2g given as an infusion 
throughout the peri-operative period.[21,33,35]  No prospective study has ever directly 
compared the efficacy of different dosing regimens.  Two previous meta-analyses showed 
a trend towards decreased peri-operative blood loss with increasing doses of TXA in 
orthopaedic patients.[35,39]  However, both of these studies, in spite of being meta-
analyses, were underpowered to demonstrate a significant treatment effect of the higher 
dose regimens.  Furthermore, neither meta-analysis reported on differences in the 
incidence of complications with higher dose regimens.  Thus, the safety and efficacy of 
different dosing regimens of TXA remains poorly defined.  Since TXA is potentially a 
prothrombotic agent, a clear understanding of the thrombotic potential of a high dose 
regimen would be critical prior to making definitive treatment recommendations. In this 
study, we plan to administer a 10mg/kg dose within 30 minutes of surgery followed by a 
10mg/kg infusion over a 4hr period to the treatment group (for patients weighting over 
100kg, a weight of 100kg will be used for the dose calculation). The control group will 
receive equal volumes of and rates of normal saline.  
 
Stratification: 
 


Stratification by known prognostic factors prior to randomization is a commonly 
employed technique to optimize balance of known prognostic factors between study 
groups.[17] Preoperative hemoglobin values have been shown to be the strongest 
predictor of transfusion following major orthopaedic surgery.[31] Enrolled patients will 
be stratified based on their preoperative hemoglobin value prior to randomization.  The 
three groups they will be stratified into will be based on previous researching 
categorizing the risk of transfusion by preoperative hemoglobin into three groups (< 13 
g/dL, 13 to 15 g/dL, and > 15g/dL).[31] 
 
Randomization: 
 
Study participants will be stratified as described above and then block randomized and 
assigned by sequentially numbered sealed opaque envelopes to one of the two treatment 
groups based on computerized selection.         
 
Blinding:   
 
The study coordinator completing the randomization and the statisticians analyzing the 
data will not be involved in the treatment of the patient.  The Investigational Pharmacy 
will provide treatment packs that are identical in appearance and differ only by their 
random number, it will not be possible for either the treating physician, or the patient to 
know the treatment regimen received.   
 
Unblinding:   
 
In general, it should not be necessary for unblinding to occur.  If a contraindication to the 
treatment regimen develops after randomization (i.e. suspicion of allergic reaction to the 
treatment), the treating physician will contact the study coordinator immediately to 
explain the reasons behind the request for unblinding. A thromboembolic event will not 
be considered a reason for unblinding, as this is a primary outcome measure. However, 
the rate of thromboembolic events will be monitored and if this rate is noted to be higher 
than the baseline rate in patients undergoing acetabular ORIF, this will trigger a safety 
evaluation. Patients whose treatment is unblinded in this manner will be excluded from 
the final data analysis.  The numbers of patients unblinded, and the reasons for the 
decisions will be specifically reported. 
 
Patient Safety Monitoring 
A data safety monitor will be appointed for this study.  This person will otherwise be 
uninvolved in the planning or execution of this trial but will have the ability to unblind 
the collected data to analyze and determine if subjects experiencing an unacceptably high 
level of adverse events.  There had not been adverse effects of tranexamic acid reported.  
For this reason, only adverse events outside of what would reasonably be expected for a 
typical post-operative trauma patient will be considered.   These adverse events will be 
assessed by the treating physicians at every follow-up appointment (2 weeks, 6 weeks, 3 
months, and 6 months), who will notify the data safety monitor within 24 hours.  If 
deemed necessary, the data safety monitor will unblind the collected data and determine 


if the study group is experiencing adverse events at a significantly higher rate or with 
greater severity than the control group.   If the risk to patients is deemed unacceptably 
high by the data safety monitor, the study will be terminated and the results will be 
published. 
 
 
Sample Size and Feasibility: 
 
Pilot Study: 
 
We plan to enroll 50 patients to test the study procedures and collect preliminary data. 
These patients will be randomized to 25 patients receiving the intervention and 25 
receiving placebo. Results from the pilot study will be used to determine the need for 
expansion to a fully powered study and to aid in seeking funding for this further 
investigation.  
 
Future Investigation:  
 
We conducted a power analysis to determine the sample size necessary to demonstrate a 
treatment effect transfusion risk. Average perioperative blood loss with acetabular ORIF 
has been reported to be approximately 1300cc as reported in the literature by one of the 
study investigators. [22] The combined rate of intraoperative and postoperative 
allogeneic transfusion has been reported to be 58% in a study performed at the study 
institution (Carolinas Medical Center).[32] We plan to power our study to detect a 30% 
difference in intraoperative and postoperative allogeneic transfusion. Assuming an alpha 
value of 0.05 and a power of 0.8 this requires a study population of 212 patients.  
 
Assuming a transfusion rate of 58% we would need 106 patients in each treatment group 
to detect a 30% decrease in transfusion rate with a power of 0.8 and an alpha of 0.05, for 
a total study population of 212 patients.  
 
Given the incidence of infection with acetabular ORIF has been reported to be 2 to 5% in 
general populations and up to 15% in morbidly obese patients, our study will likely be 
underpowered to detect changes in this outcome. [22,36] Secondary outcome measures 
including wound drainage and return to the OR for drainage and hematoma evacuation 
will also be used to study affects on wound healing.  
 
Data Collection: 
 
The data points listed below will be prospectively collected for each patient.  The 
randomization number of each patient will be included in this report, and our study 
coordinator will use this to divide the aggregate data into the three treatment groups.  
This aggregate data will then be given to our statisticians in order to complete the data 
analysis.   
 
1.  Patient Demographic Data (Age, BMI, Gender, Race, Type of Insurance).  


2.  Patient Medical Comorbidities, including Diabetes, HTN, CAD, Smoking History, 
Alcohol Use, Cardiac, Gastro-Intestinal, Genito-Urinary, Pulmonary, or Renal Disease.  
3.  Type of anesthesia used (Spinal or General). 
4.  Type of implant used in the surgery. 
5.  Operative Time.  
6.  Preoperative PT/INR and platelet count 
7.  Intraoperative EBL, as recorded in the operative note. 
8.  Number of units of PRBC transfused per patient (separately record preoperative and 
postoperative transfusions). 
9.  Hemoglobin/hematocrit laboratory values, obtained pre-operatively, pre-transfusion 
(when transfusion required) and last hemoglobin prior to discharge 
10.  Length of Hospital Stay 
11. Readmission 
12.  Incidence of sympotomatic postoperative DVT, PE, MI, and Stroke. 
13. Wound infection (superficial vs deep) 
14. Wound dehiscence 
15. Return to the OR for hematoma evacuation / wound irrigation and debridement 
16. All bacterial infection (wound, UTI, respiratory) 
 
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tranexamic acid on death, vascular occlusive events, and blood transfusion in 
trauma patients with significant haemorrhage (CRASH-2): a randomised, 
placebo-controlled trial. Lancet. 2010;376:23-32. 
 
34. 
Stulberg BN, Zadzilka JD. Blood management issues using blood management 
strategies. The Journal of Arthroplasty. 2007;22:95-98. 
 
35. 
Sukeik M, Alshryda S, Haddad FS, Mason JM. Systematic review and meta-
analysis of the use of tranexamic acid in total hip replacement. The Journal of 
bone and joint surgery. British volume. 2011;93:39-46. 
 
36. 
Tornetta, P. Displaced Acetabular Fractures: Indications for Operative and 
Nonoperative Management. J Am Acad Orthop Surg January/February 2001 vol. 
9 no. 1 18-28.  
 
37. 
Westrich GH, Bottner F, Windsor RE, Laskin RS, Haas SB, Sculco TP. 
VenaFlow plus Lovenox vs VenaFlow plus aspirin for thromboembolic disease 
prophylaxis in total knee arthroplasty. The Journal of arthroplasty. 2006;21:139-
143. 
 
38. 
Westrich GH, Sculco TP. Prophylaxis against deep venous thrombosis after total 
knee arthroplasty. Pneumatic plantar compression and aspirin compared with 
aspirin alone. The Journal of bone and joint surgery. American volume. 
1996;78:826-834. 
 
39. 
Zufferey P, Merquiol F, Laporte S, Decousus H, Mismetti P, Auboyer C, Samama 
CM, Molliex S. Do antifibrinolytics reduce allogeneic blood transfusion in 
orthopedic surgery? Anesthesiology. 2006;105:1034-1046. 


 
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Zufferey P, et al. Tranexamic acid in hip fracture surgery: a randomized 
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ICF_001.pdf: 
Tranexamic Acid 
Date: 10/17/2012 
Revision: 04/15/2013 
Expiration: 09/15/2016 
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CAROLINAS HEALTHCARE SYSTEM 
CONSENT TO PARTICIPATE IN A RESEARCH STUDY 
 
 
The Use of Tranexamic Acid to Reduce Blood Loss in Acetabular Surgery 
 
INTRODUCTION 
Dr. Karunakar and his associates in the Department of Orthopaedic Surgery at Carolinas 
HealthCare System (CHS) are asking you to participate in a research study investigating the role of 
tranexamic acid on blood loss during surgery. You are being asked to take part because you have had 
an acetabulum fracture (a break to socket of the hip joint).  The purpose of this study is to 
determine the effect of tranexamic acid on blood loss and outcome after surgery to the acetabulum.  
We will also analyze whether the use of tranexamic acid is cost effective relative to other blood loss 
management strategies.   
 
You will be one of approximately 50 people involved in this research project at CHS, and your 
participation will last for one month. 
 
Tranexamic acid is Food and Drug Administration approved for controlling bleeding in patients 
with hemophilia (a genetic bleeding disorder in which it takes a long time for the blood to clot) 
undergoing dental surgery but not for patients undergoing acetabulum surgery.  It has been used for 
reducing bleeding and the need for transfusion( the transfer of whole blood or blood products from 
one individual to another) in numerous studies of patients undergoing spine and arthroplasty (joint 
replacement) surgery. It has also been studied in trauma patients to reduce blood loss and reduce 
death.  
 
HOW THE STUDY WORKS 
If you agree to be in the study, you would be randomized to one of two treatments.  Being 
randomized means that you are put in a group by a chance process, like flipping a coin.  You won't 
know what group you are in and neither will your doctor.  We are using this method because it is 
not clear at the present time whether the proposed treatment is better than the current standard of 
care.  Your chance of receiving either treatment is one in two.  
• Group 1: Tranexamic acid 
• Group 2: Placebo (inactive medicine) 
 
Although you and your doctor will not know which treatment you are receiving, this information 
can be determined in the event of an emergency. 
 
After you sign this informed consent and agree to be part of the study, the following 
things will happen: 
• You will be assigned to one of two groups. 


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o If you are randomized to the treatment group, you will be administered a 10mg/kg 
dose of tranexamic acid within 30 minutes of surgery followed by a 10mg/kg 
infusion through an IV( through your vein) over a 4 hour period. 
o If you are randomized to the control group (placebo), you will be administered 
saline (salt water) through an IV (through your vein) during surgery as part of your 
care for your fracture.  
o You may also receive blood transfusion if needed as part of the care of your injury.  
• You will be asked about your demographic and medical history. 
• We will also record information about your surgery, such as blood transfusions and loss. 
• We will follow you 30 days after your surgery to document any complications (infections, 
clots in the blood vessels, stroke or heart attacks) you may experience.  
• We will also document how many days you spend in the hospital.  
 
As part of your care at Carolina Medical Center, your surgeon will ask you to sign a separate 
consent form for your surgery.   
 
RISKS 
The study has several risks.  First, you may be in the placebo (inactive medicine) group and will not 
receive the active medication.  Second, it is possible that you will get the new treatment but do less 
well than you would do if you had not received it.  Third, because the treatment is new for 
acetabulum fractures, we may not yet know all the side effects: something unexpected could happen.  
The known side effects are: 
 
Rare but serious 
• As with all medications, side effects may include allergic reaction.  Allergic reactions 
may range from minor itching or rash to major reactions which can result in death. 
 
Complications reported by patients, but not proven to be caused by this drug  
• Blood clot in vein   
• Pulmonary embolus, a blood clot travelling to the lung  
 
If you have problems that might be related to the (drug) (device) (treatment), your doctor may 
"break the code" to find out which group you are in.   
 
EXCLUSION CRITERIA 
• You are under the age of 18 and undergoing acetabulum surgery 
• You have  color-blindness (color vision changes used to assess toxicity) 
• You have a subarachnoid hemorrhage, bleeding between the brain and the thin tissue that 
covers it.   
• You have an active intravascular coagulation (a bleeding disorder).    


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• You have a previous history of venous thromboembolism (blood clot in the vein) or with a 
history of hypercoaguable (excessive clotting) conditions (meaning, Factor V Leiden, 
antiphospholipid antibody).  
• Prisoners 
• Pregnancy 
 
BENEFITS 
This study may or may not improve your condition.  The information gained from your case may 
benefit others with your condition. 
 
ALTERNATIVE PROCEDURE/TREATMENT 
If you choose not to participate in the study your healthcare will not be affected. Your doctor will 
discuss treatment options with you and prescribe the regimen that you agree upon.  
 
ADDITIONAL COST 
There will be no additional cost to you as a result of participating in this research.  
 
COMPENSATION     
In the event that you are harmed as a result of your participation in this study, we will provide or 
arrange for treatment as necessary.  This treatment, as well as other medical expenses, will be billed 
to you or your insurance company in the usual manner. You do not waive any legal rights by 
signing this consent form.  
 
WITHDRAWAL  
Your participation in this study is completely voluntary. You should feel under no pressure to be in 
the study.  If you decide not to be in the study, that will not in any way harm your relations with 
your doctors or with Carolinas HealthCare System.  You are free to stop being in the study if you 
change your mind after entering it.  This would not harm your relations with your doctors or 
Carolinas HealthCare System. 
 
We will tell you about new medical findings that may affect your willingness to continue in the 
study. 
 
CONFIDENTIALITY:   
The records of this study will be kept private.  In any sort of report we might publish, we will not 
include any information that will make it possible to identify a patient.  Your record for this study 
may, however, be reviewed and/or photocopied by Carolinas HealthCare System, or by 
representatives of the Food and Drug Administration or other government agencies.  To that 
extent, confidentiality is not absolute. 
 


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A description of this clinical trial will be available on www.ClinicalTrials.gov, as required by U.S. law. 
This Web site will not include information that can identify you. At most, the Web site will include a 
summary of the results. You can search this Web site at any time. 
 
AUTHORIZATION:   
If you wish to take part in this clinical study, you will be asked to sign this consent form.  It allows 
the study investigator to collect, process any relevant personal health information collected from 
you during the study.  These are activities routinely carried out during all clinical studies. 
 
You have been told that personal information about you (including sensitive personal health 
information, such as your medical history and your racial/ethnic origin if relevant to the study) will 
be reviewed, collected on a computer database, stored in electronic or manual files, audited, and/or 
otherwise processed by: 
 
the clinical study investigator, Dr. Karunakar, and research staff, 
 
regulatory or other governmental authorities of the United States and other countries, 
other persons authorized by the study sponsor, 
Carolinas HealthCare System employees, 
other persons or agencies as required by law or allowed by federal regulations. 
 
You have been told that your personal data are being collected and processed to: 
 
check your suitability to take part in the study, 
monitor your treatment with the study medication. 
 
You have been told that your personal information may be processed within the U.S. or elsewhere in 
the world or transferred to or from the U.S. for review, processing and/or storage by an associated 
company or a carefully selected third-party organization.  By signing this document, you explicitly 
consent to the transfer of your personal information, including sensitive personal information, 
collected during this clinical study, for review, processing and/or storage.  Your personal health 
information may be further shared by the groups above.  If shared by them, the information will no 
longer be covered by the Privacy Rule.  However, the groups are committed to keeping your 
personal health confidential. 
 
You may refuse this authorization to transfer your personal information.  If you choose not to agree 
to this authorization, you might be ineligible to participate in the study.  If you decide not to sign 
this authorization, that will not harm your relations with your doctors or with Carolinas HealthCare 
System.   
 


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You have the right to inspect your medical record at any time.  Your research record may be 
unavailable until the conclusion of the study.  At that point, it will be available.  Please speak with 
the study doctor if you desire to access your record. 
 
You have been told whenever your personal information is processed; it will be kept confidential 
and secure, to the best of our ability.  It will be used only for the purpose for which it was collected. 
 
This Authorization does not have an expiration date.  You have been told that according to the 
guidelines for good clinical practice, the study investigator and sponsor will keep your personal 
information for at least 6 years. If you do not withdraw this Authorization in writing, it will remain 
in effect indefinitely.  If you wish to revoke authorization to use your personal information, you will 
notify the study doctor, Madhav Karunakar, 1025 Morehead Medical Center Drive Charlotte NC 
28204 at 704-355-4638, in writing.  Some of the data obtained from your record prior to your 
revocation may still be used if considered necessary for the study.     
 
FINANCIAL INTEREST OF INVESTIGATOR   
The investigators taking part in this study have no financial interest in any commercial entity 
related to the subject of this study.  
 
QUESTIONS    
The researchers doing the study at Carolinas HealthCare System are Drs. Karunakar, Bosse, Kellam, 
Sims, Lack, Wilson, Hsu and Seymour.  You may ask them any questions you have now.  If you 
have questions later, you may contact Dr. Karunakar at: 
 
 
Department of Orthopaedic Surgery              
 
Carolinas Medical Center 
 
1000 Blythe Boulevard 
 
Charlotte, NC 28203 
 
Telephone 704-355-4638         
 
The Institutional Review Board is a group of people who review the research to protect your rights.  
If you have questions about the conduct of this study or about your rights as a research subject, you 
may call the chairperson of the Institutional Review Board of Carolinas HealthCare System for 
information regarding patients' rights in a research study.  You can obtain the name and number of 
this person by calling (704) 355-3158. 
 
 
 
 
 
 
 


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CONSENT   
I have read the above information.  I have asked any questions I had, and those questions have been 
answered.  I agree to be in this study and authorize the use of my personal health information.  Dr. 
Karunakar will give me a copy of this form.  
 
 
_________________________________       ___________________ 
_________________ 
   Patient [representative] Print Name  
 
Date 
 
 
Time 
 
 
   ________________________________       ___________________ 
 _________________ 
   Patient [representative] Signature 
 
 
Date 
 
              Time  
 
 
__________________________________       __________________ 
__________________ 
   Signature of Person Obtaining Consent 
 
Date 
 
 
   Time 
 
 
__________________________________       ___________________ 
__________________ 
   Investigator Signature 
 
 
 
Date 
 
Time 
 
 
Identity of representative: 
 
___Next of Kin 
 
 
 
 
___Parent/Guardian  
___Healthcare Power of Attorney