Clinical trial NCT03606109
Conditions: Tibial Tubercle Osteotomy
Keywords: Tibial Tubercle Osteotomy Tranexamic Acid
Sponsor: NYU Langone Health
Start date: 2018-06-26; Completion date: 2021-06-02
Enrollment: 58 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of the proposed study is to evaluate the effects of administering intravenous tranexamic acid (TXA) to patients undergoing high tibial osteotomy (HTO) and tibial tubercle osteotomy (TTO) to minimize hemarthrosis within the knee joint and post operative pain and swelling.

Detailed description:
Not Provided

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Tranexamic Acid (TXA)
Intervention descriptions: intervention 1: One gram of intravenous tranexamic acid (TXA) will be administrated before tourniquet inflation and before closure of the incision, as 1 g has been shown to be a safe amount with minimal side effects

Protocol documents:
Prot_SAP_000.pdf: 
Reducing Hemarthrosis After High Tibial Osteotomy and Tibial Tubercle Osteotomy by the Administration of Topical 
Intra-articular Tranexamic Acid (6/4/18) 
 
1 
 
Reducing Hemarthrosis in High Tibial Osteotomy and Tibial Tubercle Osteotomy 
by the Administration of Intravenous Tranexamic Acid: A Prospective, cohort 
study 
 
 
Regulatory Sponsor: 
NYU Langone Health 
Langone Orthopedic Hospital 
301 E. 17th Street 
New York, NY 10003 
 
Principal Investigator: 
 
Michael J. Alaia, MD 
Division of Sports Medicine 
New 
York 
University 
Hospital 
for 
Joint 
Diseases 
New York, NY 10003 
Office: (646) 501-7223 
 
 
 
Protocol Number: 
18-00535 
Version Date: 
June 4, 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 NCT03606109 


Reducing Hemarthrosis After High Tibial Osteotomy and Tibial Tubercle Osteotomy by the Administration of Topical 
Intra-articular Tranexamic Acid (6/4/18) 
 
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I. PURPOSE OF THE STUDY AND BACKGROUND 
 
Purpose 
The purpose of the proposed study is to evaluate the effects of administering intravenous 
tranexamic acid (TXA) to patients undergoing high tibial osteotomy (HTO) and tibial tubercle 
osteotomy (TTO) to minimize hemarthrosis within the knee joint and post operative pain and 
swelling. 
 
Rationale 
High tibial osteotomy is a procedure performed to correct varus malalignment and slow the 
progression of medial osteoarthritis or correct knee instability caused by varus malalignment1. 
Tibial tubercle osteotomy is a procedure performed to treat patellar instability or overload of the 
patella2. The tibial tubercle is a bony prominence where the patella attaches found on the anterior 
tibia, inferior to the knee joint. Both patients requiring HTO and TTOs suffer from chronic knee 
pain. During the process of an osteotomy, extensive bone bleeding can occur due to the opening 
gap3. As a result, complications of both procedures include postoperative bleeding and swelling 
of the knee joint, which prolongs healing and the rehabilitation process. 
 
Tranexamic acid (TXA) has been proposed as a solution to decrease these postoperative 
complications. TXA is a synthetic anti-fibrinolytic agent that competitively inhibits the 
activation of plasminogen to plasmin by blocking tissue plasminogen activator and at higher 
concentrations directly inhibits plasmin4,5. Plasmin, an enzyme that degrades fibrin clots, 
fibrinogen, procoagulant factors V and VIII4. Inhibition of plasmin decreases proteolytic action 
thus leading to clot formation and stabilization4. TXA is indicated in patients with hemophilia for 
short-term use (two to eight days) to reduce or prevent hemorrhage and reduce the need for 
replacement therapy during and following tooth extraction6. Administering TXA during the 
surgery will reduce the amount of plasmin in the system decreasing blood loss during and after 
the surgery. One gram of intravenous tranexamic acid (TXA) will be administrated before 
tourniquet inflation and before closure of the incision, as 1 g has been shown to be a safe amount 
with minimal side effects7.TXA has already been shown to decrease perioperative bleeding in 
total knee arthroplasty and total hip arthroplasty, without increasing the risk of deep vein 
thrombosis8-14. 
 
This study is not being conducted under an IND number and will be conducted under IND 
exemption. This investigation is not intended to be reported to the FDA in support of a new 
indication for use nor support any other significant change in the labeling or advertising for the 
drug. The investigation does not involve a route of administration or dosage level or use in a 
patient population or other factor that significantly increases the risks (or decreases the 
acceptability of the risks) associated with the use of the drug product. The route of administration 
(IV) and dosage of 1 g has been shown to be safe and effective6,7. The investigation is conducted 
in compliance with the requirements for institutional review set forth in part 56 and with the 
requirements for informed consent set forth in part 50; and The investigation is conducted in 
compliance with the requirements of 312.7.  
 


Reducing Hemarthrosis After High Tibial Osteotomy and Tibial Tubercle Osteotomy by the Administration of Topical 
Intra-articular Tranexamic Acid (6/4/18) 
 
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We hypothesize that administration of TXA will reduce perioperative bleeding in osteotomy 
procedure with minimal side effects. As a result, swelling and postoperative pain will decrease 
thus improving postoperative outcomes. While TXA has been used in various orthopedic 
surgeries to reduce bleeding, no study has investigated the efficacy of TXA during a TTO 
procedure and TXA during HTOs have limited available studies. The available literature shows 
perioperative bleeding and hematoma significantly decreased during HTO procedures3. By 
comparing high tibial osteotomy patients to tibial tubercle osteotomy patients, we will determine 
if there is a difference in efficacy or if both cohorts will be similarly affected.  
 
Study Design 
This is a single-center, prospective cohort study. Patients will be assigned to their cohorts based 
on diagnosis and appropriate treatment as determined by the surgeon. Patients will be consented 
in the study once they are scheduled for either a HTO or TTO, therefore this will not be a 
randomized study. The study is comparing blood loss and postoperative pain after TXA 
administration in patients receiving a high tibial osteotomy (HTO) to patients receiving a tibial 
tubercle osteotomy (TTO) with or without medial patello-femoral ligament (MPFL) 
reconstruction. One gram of intravenous tranexamic acid will be administered before tourniquet 
inflation and 1 gram of IV TXA before closure of the incision.  Patients will be asked on 
postoperative day 1, 2 and 7 to rate their pain according to the VAS scale. Patients will have their 
knee swelling measured immediately postoperatively and at their one-week follow up visit.  The 
swelling ratio is defined as the postoperative mean circumference of upper pole of patella and 
lower pole of patella divided by the preoperative values. 
 
Primary Objective 
The primary objective of the study is to determine if there are any differences in blood loss 
between patients undergoing high tibial osteotomy (HTO) and tibial tubercle osteotomy (TTO) 
with or without medial patello-femoral ligament (MPFL) reconstruction. 
 
Secondary Objective 
Secondary objective of the study is to determine if there is a difference in post operative pain and 
swelling between patients undergoing HTO compared to patients undergoing TTO. 
 
II. CHARACTERISTICS OF THE RESEARCH POPULATION 
 
Number of Subjects 
The total number of subjects enrolled will be approximately forty (40) patients, with 20 patients 
in the HTO cohort and 20 patients in the TTO cohort, calculated by post hoc analysis.  The 
Patients will be recruited from routine clinical practice at The NYU Langone Health, Langone 
Orthopedic Hospital, Sports Medicine Division.  
 
Gender of Subjects  
Men and women will be included in this study. 
 
Age of Subjects 
Subjects included study will be at least 18 years of age. 


Reducing Hemarthrosis After High Tibial Osteotomy and Tibial Tubercle Osteotomy by the Administration of Topical 
Intra-articular Tranexamic Acid (6/4/18) 
 
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Racial and Ethnic Origin 
There are no enrollment restrictions based on race or ethnic origin. 
 
Inclusion Criteria 
Patients will be screened for eligibility using the following criteria. All study subjects must meet 
the following inclusion criteria: 
• Patients undergoing a high tibial osteotomy (HTO)  
• Patients undergoing tibial tubercle osteotomy (TTO) with or without medial patello-
femoral ligament (MPFL) reconstruction 
• Patients ages 18-60, inclusive 
 
Exclusion Criteria 
Patients meeting the following criteria will be excluded from participation in this study: 
• Legally incompetent or mentally impaired (e.g., minors, Alzheimer’s subjects, dementia, 
etc.) 
• Younger than 18 years of age 
• Older than 60 years of age 
• Any patient considered a vulnerable subject including: pregnant women or fetuses, 
children, cognitively impaired adults, prisoners 
• history of coagulation abnormalities and thromboembolic disease or current abnormal 
coagulation test values  
• history of stroke or acute coronary syndromes within 3 months before surgery 
• Preoperative (chronic) anticoagulation therapy 
• Abnormal coagulation profile 
• Renal failure (serum creatinine > 250 μmol/L [2.83 mg/dL]) or liver cirrhosis  
• Sickle cell disease 
• Patients with a history of hypersensitivity to Percocet and/or TXA 
 
Vulnerable Subjects 
We do not intend to enroll vulnerable subjects. 
 
Subject withdrawal criteria.  Patients are free to withdraw at any time from the study.   
 
III. METHODS AND PROCEDURES 
 
Methods and Procedures  
Patients indicated and scheduled for a high tibial osteotomy or tibial tubercle osteotomy with or 
without medial patello-femoral ligament reconstruction will be identified from faculty surgeon 
case logs at the NYU Langone Health, Langone Orthopedic Hospital Sports Medicine Division.   
After informed consent is obtained, a chart review of patients’ medications and past medical 
histories will be reviewed based on their electronic medical records to identify any current pain 
medications or exclusion criteria. Patients will be in the study for 1 week, until their first follow 
up visit. 
 


Reducing Hemarthrosis After High Tibial Osteotomy and Tibial Tubercle Osteotomy by the Administration of Topical 
Intra-articular Tranexamic Acid (6/4/18) 
 
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Patients will be given 1 gram of intravenous tranexamic acid (TXA) before tourniquet inflation 
and 1 gram of IV TXA before closure of the incision. Immediate post-operative management 
will not be affected by this study. The study team will not be blinded to the study as there is no 
randomization to each cohort.  All patients will receive a standardized regimen of aspirin for 
DVT prophylaxis and Percocet for pain management, which is standard of care post-operative 
treatment.  
 
Information to be recorded pre-operatively includes age, sex, height, weight, BMI, and American 
Society of Anesthesiology (ASA) classification. Intra-operative information will also be 
recorded, including operative time, and estimated blood loss. During the surgery, a suction 
device is utilized to remove excess blood from the surgical site and sucked into the suction drain 
and placed into a measuring cup. We will measure the perioperative blood loss by look at the 
measuring cup and seeing how much blood is inside.  Knee swelling postoperatively will be 
measured using the swelling ratio. The swelling ratio was defined as the circumference of the 
operative limb divided by the circumference of the contralateral limb. Pain severity scores at rest 
will be assessed by use of a visual analog scale (VAS; 0 = no pain, 10 = worst pain imaginable) 
at 0.5, 1, 1.5, 2, 4, 6, 24, and 48 hours as well as 7 days after surgery. Percocet consumption will 
be recorded at 24 hours, 1 day, 2 days and 7 days after surgery. Incidence of TXA-related side 
effects (nausea/vomiting, itching, anxiety, increased thirst, rapid heartbeat) in the first 24 hours 
will be noted. Time to discharge from the post-anesthesia care unit (PACU) and time to 
discharge from the hospital will be recorded.  
 
 
 Analysis and Data Monitoring 
Data monitoring will be done by Dr. Michael Alaia, the principal investigator. He will review the 
following accumulated data quarterly.   
He will monitor whether or not: 
1. Collection and storage of patient data was performed in a sensitive and secure 
manner, as defined in the informed consent form and protocol, ensuring information 
is stored on REDCap. 
2. All study activities were conducted with primary emphasis on patient care and 
wellbeing, ensuring the patients are not in discomfort and have an abnormally high 
VAS following the surgery. 
3. If there were any adverse events, and if so were addressed appropriately and per 
protocol  
4. The risk/benefit to patients has remained the same throughout the course of the study. 
 
The study will be stopped if there are unexpected severe AE’s in more than one patient. Adverse 
events will be defined as negative reactions to the intravenous TXA during or after surgery, 
including seizures, vision problems. We will submit summaries of data and safety monitoring 
annually.   
 
Data Analysis  
According to a post hoc power analysis calculating the effect size using our preliminary data, 
>15 patients are required with d=0.6 to obtain a power of 0.80 and an alpha value of 0.05. 
Therefore we are including an additional 5 patients per group to account for patients that may be 


Reducing Hemarthrosis After High Tibial Osteotomy and Tibial Tubercle Osteotomy by the Administration of Topical 
Intra-articular Tranexamic Acid (6/4/18) 
 
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lost to follow up. Statistical analysis will be performed using chi-squared and/or fisher’s exact 
testing depending on size for binary variables.  Continuous variables will be compared with 
paired t-tests if the data is approximately normally distributed.  If the data is not normally 
distributed, Mann-Whitney tests will be used.  All protected health information will be removed 
prior to statistical analysis. We will use patient subjective pain, perioperative blood loss and knee 
swelling data as statistical endpoints. Subjective pain will be measured with the VAS (visual 
analogue scale), perioperative blood loss will be measured looking at blood loss from the suction 
drain after surgery. The swelling ratio is defined as the postoperative mean circumference of 
upper pole of patella and lower pole of patella divided by the preoperative values according to 
our previous study. The endpoints must be statistically significant between the two cohorts to 
show TXA is effective. 
 
 
Data Storage and Confidentiality 
Data recorded from this study will be organized in RedCap and maintained on the department’s 
secure password-protected research drive until the data are de-identified. Participant medical 
information will only be available to the principal investigator and research staff as necessary for 
data analysis. All patient health information will be de-identified and assigned a code. 
Information linking participants’ names, social security numbers and medical record numbers 
will be stored in a secure location separate from the medical information. This information will 
be destroyed at study closure. 
 
Adverse Event Reporting 
Information about any breach of confidentiality will be documented in the electronic data 
collection system and/or on the paper CRFs, as appropriate. It will be the responsibility of the 
Principal Investigator to report any Serious Adverse Event (SAE) that occurs during the data 
collection to the Institutional Review Board (IRB) within the timeframe specified by NYU SoM. 
 
IV. RISK/BENEFIT ASSESSMENT 
 
Risk 
This study involves risk of medication side effects as well as a breech of confidentiality. 
Intravenous TXA can cause the following side effects: 
• Anxiety 
• blurred vision 
• changes in vision 
• chest pain 
• confusion 
• cough 
• dizziness or lightheadedness 
• fainting 
• fast heartbeat 
• greatly increased or decreased frequency of urination or amount of urine 
• increased thirst 
• loss of appetite 
• nausea or vomiting 


Reducing Hemarthrosis After High Tibial Osteotomy and Tibial Tubercle Osteotomy by the Administration of Topical 
Intra-articular Tranexamic Acid (6/4/18) 
 
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• numbness of the hands 
• pain, redness, or swelling in the arm or leg 
• sudden shortness of breath or troubled breathing 
 
Rare side effects include: 
• Convulsions or seizures 
• Orthostatic hypotension 
• sweating 
• trouble seeing 
• unusual tiredness or weakness.  
 
Protection against Risks  
The patients will stay in the recovery unit a minimum of 3 hours after surgery as the mean 
duration of the effect of TXA is 3 hours and be monitored by the recovery unit nurses15,16. 
Patients will be instructed to call the principal investigator and visit the emergency department if 
there is are any symptoms of calf swelling or chest pain within the first seven days following 
surgery. 
 
All patients will be de-identified and given a code. Information linking the patient codes to the 
participants’ names and medical record numbers will be stored in a secure location separate from 
the medical information.  Access to the information linking the linkage codes with participant 
identifiers shall be restricted.   
 
Potential Benefits to the Subjects  
Patients may experience less pain post-operatively, and may require less narcotics use, which has 
a steeper side-effect profile. However, these benefits cannot be guaranteed. 
 
Additionally, it is the hope of the research team that results of this study will benefit future 
patients and their physicians by providing more information regarding the efficacy of TXA 
during surgery.  This will allow for a more open and informed dialogue, and possibly a change in 
standard of care.  
 
 
V. INVESTIGATOR’S QUALIFICATIONS AND EXPERIENCE 
 
The CV, medical license, and human subjects’ tutorial completion report are attached for all 
investigators who are participating in this study.  All research personnel have medical research 
experience and are qualified to participate in this quality study. Most importantly, staff have been 
properly educated and certified with CITI training to conduct research in a matter that will 
maintain full patient confidentiality. The research coordinator for this study is trained in GCP 
principles and practices and will be responsible for compliance with GCP guidelines for all study 
investigators and research assistants. 
 
VI. SUBJECT IDENTIFICATION, RECRUITMENT AND CONSENT/ASSENT 
 
Method of Subject Identification and Recruitment 


Reducing Hemarthrosis After High Tibial Osteotomy and Tibial Tubercle Osteotomy by the Administration of Topical 
Intra-articular Tranexamic Acid (6/4/18) 
 
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Case logs of participating faculty in the NYU Langone Health, Langone Orthopedic Hospital, 
Sports Medicine Division will be examined for patients that are scheduled for HTO or TTO with 
or without MPFL reconstruction. All potential subjects will be patients of the faculty in the NYU 
Langone Health, Langone Orthopedic Hospital, Sports Medicine Division.   
 
Process of Consent 
Written consent will be obtained from subjects who are eligible candidates for HTOs and TTOs 
based upon their medical condition (as determined by their physician). The consent process will 
take place during the office visit when it is determined necessary to perform the procedure—at 
which time the investigator has determined subject’s voluntary participation has been upheld. 
Subjects will be informed about the study and the intended purpose. They will be given the 
opportunity to ask questions and receive thorough explanations. They will be made aware of the 
possible risks and anticipated benefits. They will also be informed of alternative procedures. 
Subjects will then be given another opportunity to ask questions and agree or disagree to consent. 
 
Subject Capacity 
All subjects enrolled in this study will have capacity to provide informed consent. 
 
Subject/Representative Comprehension.  
Before obtaining consent, study staff will educate patients about their condition and the study. 
Subjects will be asked to explain the study and its purpose, the risks and benefits of their 
participation and the procedures of withdrawal from the study to be certain they have a full 
understanding of the information before consent is obtained. 
 
Debriefing Procedures 
No information will be withheld from the subject. 
 
Consent Forms 
Informed consent forms will be used for this study and stored in a locked cabinet accessible only 
to active study team members. 
 
Documentation of Consent 
Consent will be obtained by the approved study staff. It will be structured to allow full 
understanding of the study by providing sufficient time for review. All questions will be 
answered and the risks/benefits will be thoroughly explained.  
 
Costs to the Subject 
Subjects will not incur any additional financial costs as a participant in this study. 
 
Payment for Participation  
No payments/reimbursements will be provided to subjects for their participation in this study. 
 
 
VII. References 
1. 
Sharma L, Song J, Felson DT, Cahue S, Shamiyeh E, Dunlop DD. The role of knee alignment in 
disease progression and functional decline in knee osteoarthritis. JAMA. 2001;286(2):188-195. 


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Intra-articular Tranexamic Acid (6/4/18) 
 
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2. 
Grawe B, Stein BE. Tibial Tubercle Osteotomy: Indication and Techniques. J Knee Surg. 
2015;28(4):279-284. 
3. 
Suh DW, Kyung BS, Han SB, Cheong K, Lee WH. Efficacy of Tranexamic Acid for Hemostasis in 
Patients Undergoing High Tibial Osteotomy. J Knee Surg. 2018;31(1):50-55. 
4. 
Chen JY, Chin PL, Moo IH, et al. Intravenous versus intra-articular tranexamic acid in total knee 
arthroplasty: A double-blinded randomised controlled noninferiority trial. Knee. 2016;23(1):152-
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5. 
Huang Z, Ma J, Shen B, Pei F. Combination of intravenous and topical application of tranexamic 
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Karaaslan F, Karaoglu S, Yurdakul E. Reducing Intra-articular Hemarthrosis After Arthroscopic 
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7. 
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Alshryda S, Sarda P, Sukeik M, Nargol A, Blenkinsopp J, Mason JM. Tranexamic acid in total 
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Ho KM, Ismail H. Use of intravenous tranexamic acid to reduce allogeneic blood transfusion in 
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Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W. Use of antifibrinolytic 
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15. 
Karaaslan F, Karaoglu S, Mermerkaya MU, Baktir A. Reducing blood loss in simultaneous 
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Camarasa MA, Olle G, Serra-Prat M, et al. Efficacy of aminocaproic, tranexamic acids in the 
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