Efficacy of Tranexamic Acid in Foot and Ankle Surgeries- a Randomized Controlled Trial.
Phase: PHASE4
Conditions: Foot and Ankle Surgeries, Bunion
Sponsor: Icahn School of Medicine at Mount Sinai

 
Protocol Name: 
EFFICACY OF TRANEXAMIC ACID IN FOOT AND ANKLE 
SURGERIES - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD 347-569-4816 
ETTORE VULCANO MD 
 
Date Revised: 
7/23/2017 
Study Number: 
 IF# 2089572, GCO#17-04301 
 
1 
Revised 9/2/14 
HRP-503 PROTOCOL TEMPLATE  
 
Note that, depending on the nature of your research, certain questions, directions, or entire sections below 
may not be applicable. Provide information if and when applicable, and in cases where an entire section is not 
applicable, indicate this by marking the section “N/A”.  Do not delete any sections. 
 
For any items below that are already described in the sponsor’s protocol, the investigator’s protocol,  the 
grant application, or other source documents, you may simply reference the title and page numbers of these 
documents in the sections below, rather than cutting and pasting into this document. Do not refer to the 
Sample Consent document, or information on the application form in this document.. 
 
Keep an electronic copy of this version of the document. You will need to modify this copy when making 
changes. 
 
Brief Summary of Research (250-400 words):  
In foot and ankle surgery, the prevention of postoperative hematoma in a confined 
space in the wound has a crucial impact on perioperative outcomes.  There has been 
growing emphasis on the role of antifibrinolytics to minimize bleeding and the 
formation of postoperative hematoma.  Approximately 20% of all foot and ankle 
fractures are open. Excellent operative field without measurable bleeding remain 
prerequisite of most orthopedic procedures. Increase blood loss can increase the risk 
of infection, hematoma formation and wound complications. Presence of blood in 
synovium not only has direct corrosive effects but also causes increased intra 
capsular pressure leading to capsular fibrosis culminating as ankyloses.  
                
Traditionally, tourniquets are employed to optimize surgical field visualization 
thereby limiting operative duration and improving technical precision. There are 
several unwanted effects that can arise from use of tourniquet like neurapraxia, 
vascular injury, post operative swelling etc. Hence there is a growing interest in 
achieving the same operative goals without the use of tourniquet. 
 
Antifibrinolytics can be utilized to achieve a blood sparing effect. Its efficacy in 
reducing intra operative and post operative blood loss is well documented in cardiac 
surgery, joint replacement surgery, and spine surgery. Tranexamic acid is a synthetic 
antifibrinolytic drug that competitively blocks the lysine-binding sites of 
plasminogen, plasmin and tissue plasminogen activator, thereby delaying 

 
Protocol Name: 
EFFICACY OF TRANEXAMIC ACID IN FOOT AND ANKLE 
SURGERIES - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD 347-569-4816 
ETTORE VULCANO MD 
 
Date Revised: 
7/23/2017 
Study Number: 
 IF# 2089572, GCO#17-04301 
 
2 
Revised 9/2/14 
fibrinolysis and blood clot degradation. It has been effectively used as intravenous 
(IV), oral, topical, as well as intra articular routes of administration. The effects of 
IV administration lasts 8-17 hours after the initial dose. Orthopedic surgeons have 
incorporated TXA into multiple elective surgeries as a means of reducing blood loss 
and transfusion requirements.  
 
Effectiveness of Tranexamic acid (TXA) in postoperative outcomes is unknown in 
foot and ankle surgeries. The aim of this study is to evaluate effectiveness of 
intraoperative doses of intravenous TXA in reducing postoperative bleeding and 
hematoma formation after foot and ankle surgeries.  
 
 
1)Objectives 
Research Question: Does intraoperative administration of intravenous TXA reduce 
postoperative bleeding and hematoma formation after foot and ankle surgeries? 
Primary outcome: The incidence of wound complications classified as dehiscence, 
hematoma, necrosis and infection.  Wound healing time and length of stay will be 
evaluated.  The first follow up at surgeon’s office will be included.  
Secondary outcome: The amount of intra operative and post operative blood loss 
during the first 24 hours in patients undergoing foot and ankle surgeries. Post-
operative complete blood count (CBC), duration of surgery and intra operative fluid 
resuscitation will be recorded. Intraoperative and post operative narcotic 
consumption.  
 
2)Background 
See above. Effectiveness of Tranexamic acid (TXA) is unknown in foot and ankle 
surgeries. The aim of this study is to evaluate effectiveness of intravenous TXA in 
reducing post operative blood loss during foot and ankle surgeries.  
 
     3)Setting of the Human Research 

 
Protocol Name: 
EFFICACY OF TRANEXAMIC ACID IN FOOT AND ANKLE 
SURGERIES - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD 347-569-4816 
ETTORE VULCANO MD 
 
Date Revised: 
7/23/2017 
Study Number: 
 IF# 2089572, GCO#17-04301 
 
3 
Revised 9/2/14 
Prospective triple blinded randomized control trial in patients undergoing foot and 
ankle surgeries. The research study will take place at Mount Sinai West hospital. 
The site PI is Yan Lai, MD, MPH. 
 
 
4)Resources Available to Conduct the Human Research 
For n=200, the feasibility of recruitment is manageable. Recruitment will be done 
through a coordination of the operating schedule and the surgeon’s office.  Patients 
presenting for preoperative visits at the surgeon’s office or the preoperative joint 
clinic will be approached. The surgeon will also provide study information 
(protocol, consent, general information) to patients in the surgeon’s office.  After 
confirmation on the operating schedule, patients will be provided detailed 
instructions the day before surgery and the final consent will be obtained at the 
surgeon’s office or joint clinic for patients at Mount Sinai West hospital. On the day 
of the surgery, the subject will meet the research team in the holding area.  The team 
will finalize participation and ask the subject about the signed consent forms and 
answer any additional questions.   The staff members on this protocol are all 
employees of Mount Sinai and will either be a resident or attending physicians that 
are included on the IRB protocol. There are three primary members of the research 
personnel: 
     a)Yan Lai, MD, MPH – Roles for Dr. Lai in this study include serving as primary 
investigator responsible for study design and planning, data collection, subject 
recruitment, manuscript writing and preparation, data analysis, safety monitoring, 
and responding to adverse events and/or complications. He is certified in PPHS/IRB 
protocols, all Citi/IRB required training in human subject protection, and has prior 
clinical research experience. He is also a board certified anesthesiologist and 
assistant professor of anesthesiology with the Icahn School of Medicine and the 
Mount Sinai Health System. 
 
     b) Poonam Pai B.H MD – Roles for Dr. Pai include serving as primary research 
coordinator involved in data collection, subject recruitment, manuscript writing and 
preparation, data analysis, safety monitoring, and responding to adverse events 

 
Protocol Name: 
EFFICACY OF TRANEXAMIC ACID IN FOOT AND ANKLE 
SURGERIES - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD 347-569-4816 
ETTORE VULCANO MD 
 
Date Revised: 
7/23/2017 
Study Number: 
 IF# 2089572, GCO#17-04301 
 
4 
Revised 9/2/14 
and/or complications.  She has completed all of her required CITI training to be IRB 
certified and has experience in clinical research. In addition she has been a resident 
physician in anesthesiology with the Icahn School of Medicine in good standing for 
the previous three years going on her fourth. 
 
c) Ettore Vulcano MD- Roles for Dr Vulcano in this study include serving as co-
investigator responsible for study design and planning, data collection, subject 
recruitment, manuscript writing and preparation, data analysis, safety monitoring, 
and responding to adverse events and/or complications. He is certified in PPHS/IRB 
protocols, all Citi/IRB required training in human subject protection, and has prior 
clinical research experience. He is also a board certified orthopedic surgeon and 
assistant professor, department of Orthopedic surgery with the Icahn School of 
Medicine and the Mount Sinai Health System. 
 
There are institutional processes to ensure that all persons assisting with the protocol 
will be well informed.  The research personnel will conduct regular meetings and 
department email updates to review the results and safety data of the study.  The 
research personnel will initiate the formation of a safety monitoring board for 
adverse effects, complications, or complaints from patient subjects. 
 
  5) Study Design 
Prospective triple blinded randomized control trial. The surgeon will also provide 
study information (protocol, consent, general information) to patients in the 
surgeon’s office.   Recruitment will be done through a coordination of the operating 
schedule and the surgeon’s office.  Patients presenting for preoperative visits at the 
surgeon’s office or the preoperative joint clinic will be approached. On the day of 
the surgery, the subject will meet the research team in the holding area.  The team 
will finalize participation and ask the subject about the signed consent forms and 
answer any additional questions.  All patients will be provided with copies of the 
IRB protocol and consent if they wish to have it. Copy of the consent form will be 
sent in a secured email to the potential subject. The email will be secured by 

 
Protocol Name: 
EFFICACY OF TRANEXAMIC ACID IN FOOT AND ANKLE 
SURGERIES - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD 347-569-4816 
ETTORE VULCANO MD 
 
Date Revised: 
7/23/2017 
Study Number: 
 IF# 2089572, GCO#17-04301 
 
5 
Revised 9/2/14 
entering in [SECURE] in the e-mail subject line.  Once recruited blinding 
assessments will be done by the study team.  
 
Patients will be assigned randomly using a computer- generated table of numbers to 
either TXA group (Tranexamic acid group) or placebo (saline group). Patients 
assigned to TXA group will receive 10mg/kg IV TXA in a 100cc normal saline bag 
at the time of induction and a second dose prior to skin closure. Patients in the 
placebo group will receive 100cc normal saline IV at the time of induction and a 
second dose prior to skin closure. Otherwise, the patient, surgeon, and 
anesthesiologist in the case will be blinded.   
 
a) Recruitment methods: Patients will be recruited and consented at the surgeons 
office or pre-operative testing/Joint clinic. 
 
b) Inclusion and Exclusion Criteria 
 Inclusion criteria: ASA (American Society of Anesthesiology) class I-IV, age 18-     
75.  
Exclusion criteria: ASA class V, patient refusal, patients with known coagulopathy 
disorder, renal insufficiency, hepatic dysfunction, serious cardiac disease, patients 
receiving antiplatelet and/or anticoagulant drugs, or an allergy to TXA or will be 
excluded.  
 
c)Number of Subjects 
 
We intend to recruit 200 patients. 
Based on a confidence level of 99% with a Z score of 2.58, standard deviation of .5 
and a confidence interval of 10% our sample size should be 166. For ease of 
statistical calculations we rounded up to 200 patients. Literature search reveals only 
one previous study where TXA has been used in calcaneal fractures. Xie et al 
concluded in a study with 90 patients that TXA reduces post operative blood loss. 
We intend to use a higher sample size to see any statistical significance. 
 

 
Protocol Name: 
EFFICACY OF TRANEXAMIC ACID IN FOOT AND ANKLE 
SURGERIES - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD 347-569-4816 
ETTORE VULCANO MD 
 
Date Revised: 
7/23/2017 
Study Number: 
 IF# 2089572, GCO#17-04301 
 
6 
Revised 9/2/14 
ss = 
Z 2 * (p) * (1-p) 
c 2 
 
Where: 
Z 
= 
Z 
value 
(2.58 
for 
99% 
confidence 
level)  
p = percentage picking a choice, expressed as decimal (.5 used for sample size 
needed) 
c = confidence interval, expressed as decimal  (e.g., .01= ±1) 
 
Sample size= [(2.58^2)(.5)(.5)]/(.1^2)=166 subjects 
For effect size, we expect a Cos d medium effect of 0.5.  
Intergroup comparisons will be performed using the Mann-Whitney U test. 
Qualitative data will be compared using the chi-square test or Fisher’s exact test. 
Only p < .05 will be considered statistically significant.  
 
 
d)Study Timelines 
      2018-2019 and subsequent data analysis. The subject’s participation will be from 
time of enrollment in the pre-operative period until first postoperative day. The first 
follow up visit at the surgeons office will be included as well. Estimated date of 
enrollment completion will be when 200 eligible subjects are enrolled in final data 
analysis.  Estimate date for study completion will be June 2018. 
 
 
 
 
 

 
Protocol Name: 
EFFICACY OF TRANEXAMIC ACID IN FOOT AND ANKLE 
SURGERIES - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD 347-569-4816 
ETTORE VULCANO MD 
 
Date Revised: 
7/23/2017 
Study Number: 
 IF# 2089572, GCO#17-04301 
 
7 
Revised 9/2/14 
e)Endpoints 
Conclusion of data analysis and evaluation of significance of findings, as measured 
by primary and secondary outcomes listed under Objectives (item #1) for purposes 
of quality improvement. 
 
f)Procedures Involved in the Human Research 
Prospective randomized controlled trial and data analysis only. TXA group and 
placebo group. Intraoperative care of the patient will be provided by an anesthesia 
team member who is a part of the Mount Sinai System. The anesthesia provider will 
not be aware of the randomization of the patient.  Standard post-operative orders 
will be written for patients during their time in the PACU. 
 
g)Specimen Banking 
 N/A  
 
h)Data Management and Confidentiality 
Data collected in excel file to be de-identified after initial collection. Excel file be 
subsequently encrypted and shared only between the above listed investigators via 
secure Mt. Sinai (chpnet) electronic mail.   
The information included in the data will be medical record number, age, gender, 
ASA class, type of surgery, duration of surgery, the amount of intra operative and 
post operative blood loss during the first 24 hours in patients will be collected. 
Wound complications (eg dehiscence, hematoma, necrosis and infection), wound 
healing time and length of stay will be evaluated. Post operative complete blood 
count will be recorded. The first follow up at surgeon’s office will be the other data 
collected. 
Only the research personnel will have access to the data. The data will be stored as a 
hard copy files and on a secure spreadsheet. The research personnel is responsible 
for the receipt of the data. The PI will keep the hard copies secure and any electronic 
data will be encrypted. No personal identifiers will be used. The data will undergo 
statistical analysis 

 
Protocol Name: 
EFFICACY OF TRANEXAMIC ACID IN FOOT AND ANKLE 
SURGERIES - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD 347-569-4816 
ETTORE VULCANO MD 
 
Date Revised: 
7/23/2017 
Study Number: 
 IF# 2089572, GCO#17-04301 
 
8 
Revised 9/2/14 
 
 
i)Provisions to Monitor the Data to Ensure the Safety of Subjects 
      Part I: Elements of Data and Safety Monitoring Plan 
MSSM Principal Monitor: 
 
Last Name: Lai 
First Name: Yan 
Academic Title: Attending Physician, Assistant Professor 
Department: Anesthesiology 
Mailing Address: Mount Sinai West 1000 10th Avenue, New York, NY 10019 
Phone: 212-523-6915 
Fax:  
E-mail: ylai@chpnet.org 
 
 
MSSM Additional Monitor: 
 
Last Name: Pai B.H 
First Name: Poonam 
Academic Title: Research Personnel, Physician 
Department: Anesthesiology 
Mailing Address: Mount Sinai West 1000 10th Avenue, New York, NY 10019 
Phone: 212-523-6915 
Fax:  
E-mail: phebbalasankatte@chpnet.org 
 
MSSM Additional Monitor: 
 
Last Name: Vulcano 
First Name: Ettore 
Academic Title: Attending Physician, Assistant Professor 
Department: Orthopedic Surgery 
Mailing Address: 425, west 59th street, 5th floor, New York, NY 10019 
Phone: 212-523-7342 
Fax:  
E-mail: Ettore.vulcano@mountsinai.org 
 
 

 
Protocol Name: 
EFFICACY OF TRANEXAMIC ACID IN FOOT AND ANKLE 
SURGERIES - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD 347-569-4816 
ETTORE VULCANO MD 
 
Date Revised: 
7/23/2017 
Study Number: 
 IF# 2089572, GCO#17-04301 
 
9 
Revised 9/2/14 
The principal monitor is a board certified anesthesiologist thus minimizing the risk 
to the subjects and further optimizing their health and wellbeing. Adverse events 
will be monitored as a standard of care everyone receives regardless of participation 
in the study. The safety and data information will be reviewed on a daily basis until 
the desired sample size is achieved. All temporary and/or permanent suspensions 
will be reported. Prospective chart review for quality data analysis without potential 
for danger to subjects. 
All anesthesiologists involved in patient care will be prepared for the prevention and 
rescue for any complications involving IV TXA.  
 
j) Withdrawal of Subjects 
 Patients may withdraw from the study at any given time by contacting any member 
of the research study group. Data will not be collected on patients who wish to 
withdraw. Patients do not need to withdraw consent in writing. 
 
6) Risks to Subjects 
If patients are injured or made sick from taking part in this research study, medical 
care will be provided. Generally, this care will be billed to the patient or their 
insurance in the ordinary manner and the patient will be responsible for all treatment 
costs not covered insurance, including deductibles, co-payments and coinsurance.  
This does not prevent the patient from seeking payment for injury related to 
malpractice or negligence. Contact the investigator for more information. 
 
As with any medication, there is a possibility of an allergic reaction. Although rare, 
possible complications include hypersensitivity reaction, bleeding or local site 
infection, and chance of any vascular event.  There is a possible risk of private 
information with procedures in place to minimize the risk. 
 
7)Provisions for Research Related Harm/Injury 
If patients are injured or made sick from taking part in this research study, medical 
care will be provided. Generally, this care will be billed to the patient or their 
insurance in the ordinary manner and the patient will be responsible for all treatment 

 
Protocol Name: 
EFFICACY OF TRANEXAMIC ACID IN FOOT AND ANKLE 
SURGERIES - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD 347-569-4816 
ETTORE VULCANO MD 
 
Date Revised: 
7/23/2017 
Study Number: 
 IF# 2089572, GCO#17-04301 
 
10 
Revised 9/2/14 
costs not covered insurance, including deductibles, co-payments and coinsurance.  
This does not prevent the patient from seeking payment for injury related to 
malpractice or negligence. Contact the investigator for more information. 
 
8)Potential Benefits to Subjects 
It is important to know that you may not get any benefit from taking part in this 
research.  Others may not benefit either. However, possible benefits may be 
improved with knowledge about how the reduced blood loss helps in better surgical 
outcome.  
 
9)Provisions to Protect the Privacy Interests of Subjects 
Patients will be appropriately educated about the research study. Any questions or 
concerns they have will be adequately addressed and patients will have the option to 
decline participation. Patients will be given as much time as they need to review the 
consent form. The study personnel will be approaching the subjects. Privacy will be 
maintained by not including any identifiers such as names or addresses in the data 
collected.  
The identities of human subjects whose data is being studied will be de-identified as 
per HIPAA Privacy Rule. 
 
10)Economic Impact on Subjects 
Patients will not incur any additional cost for participating in the study. The 
medications used are part of a standard anesthetic regimen that will be billed to 
subject’s insurance as bundled standard of anesthesia care.  The cost of the 
procedure is overall unaffected.   
 
11)Payments to Subjects 
 Patients will not be reimbursed for their participation. 
 
 

 
Protocol Name: 
EFFICACY OF TRANEXAMIC ACID IN FOOT AND ANKLE 
SURGERIES - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD 347-569-4816 
ETTORE VULCANO MD 
 
Date Revised: 
7/23/2017 
Study Number: 
 IF# 2089572, GCO#17-04301 
 
11 
Revised 9/2/14 
 
12)Consent Process 
Informed consent will be obtained prior to the procedure. Both the HRP-090 (SOP) 
Informed Consent Process for Research and the HRP-091 (SOP) Written Documentation of Consent 
will 
be 
followed 
by 
the 
study 
team. 
These 
documents 
are 
both 
available 
at 
http://icahn.mssm.edu/research/resources/program-for-the-protection-
of-human-subjects/irb-members-palette. 
 
13)Process to Document Consent in Writing 
The patients will receive a paper copy of the IRB approved consent packet and will 
sign in the designated areas to confirm consent of participation.  They will have the 
option of have a copy of the consent and may ask for a personal copy of the consent.  
 
14)Vulnerable Populations 
Indicate specifically whether you will include (target) or exclude each of the following 
populations: 
I
n
c
l
u
d
e 
E
x
c
l
u
d
e 
Vulnerable Population Type 
 
X 
Adults unable to consent 
 
X 
Individuals who are not yet adults (e.g. infants, children, teenagers) 
 
X 
Wards of the State (e.g. foster children) 
 
X 
Pregnant women 
 
X 
Prisoners 
 
15)Multi-Site Human Research (Coordinating Center) 

 
Protocol Name: 
EFFICACY OF TRANEXAMIC ACID IN FOOT AND ANKLE 
SURGERIES - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD 347-569-4816 
ETTORE VULCANO MD 
 
Date Revised: 
7/23/2017 
Study Number: 
 IF# 2089572, GCO#17-04301 
 
12 
Revised 9/2/14 
This study will be performed within the Mount Sinai West Hospital. No additional 
centers will be involved. 
 
16)Community-Based Participatory Research 
This does not apply to our study. 
 
17)Sharing of Results with Subjects 
Results will not be shared with the patients since the study will take time to 
complete.  Patients can request results if they contact the PI by writing. 
 
18)External IRB Review History 
This does not apply to our study. 
 
19)Control of Drugs, Biologics, or Devices  
Not applicable.  IV TXA are routinely used in orthopedic surgeries.