Clinical trial NCT04541303
Conditions: Postoperative Wound Haemorrhage
Keywords: tranexamic acid hemostasis hemorrhagic complication bleeding complication Mohs micrographic surgery granulating wound granulating defect
Sponsor: University of Missouri-Columbia
Start date: 2020-10-08; Completion date: 2021-12-30
Enrollment: 124 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Bleeding after Mohs micrographic surgery for skin cancer is a low risk complication that can occur. This study aims to determine the effect of a drug, often used to reduce bleeding, called tranexamic acid when applied topically to the skin wound after surgery.

Detailed description:
To perform a prospective randomized controlled trial to determine the hemostatic effect of TXA soaked gauze (intervention) versus normal saline soaked gauze (control) when applied to granulating defects in the setting of Mohs micrographic surgery.

Patients meeting inclusion criteria will be randomized into two arms once enrolled in the study on the day of their Mohs micrographic surgery (MMS).

One arm will serve as the control group and will receive normal saline soaked telfa pads to the wound bed upon completion of MMS.

A second arm will receive TXA 25mg/ml at a volume of 1ml/cm2 soaked telfa pads to wound bed upon completion of MMS.

In both arms, the telfa pads will have a standard pressure dressing placed overtop.

Arms: arm 1: Topical application of tranexamic acid to granulating wound defect status post Mohs micrographic surgery. arm 2: Topical application of normal saline to granulating wound defect status post Mohs micrographic surgery.
Interventions: intervention 1: Tranexamic acid intervention 2: normal saline
Intervention descriptions: intervention 1: tranexamic acid diluted to concentration of 25ml/mg intervention 2: 0.9% sodium chloride

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
Title: 
Randomized Study on the Topical Application of Tranexamic Acid to 
the Wound Bed of Granulating Defects for Hemostasis in the Setting 
of Mohs Micrographic Surgery 
 
NCT #: 
04541303 
 
Date:  
20-MAY-2021 
 
 


PI: Nicholas Golda, MD 
 
IRB# 2025444 
 
 
V3; 5/20/21 
TITLE:  Randomized study on the topical application of tranexamic acid to wound 
bed for hemostasis in the setting of Mohs micrographic surgery 
 
1. ABSTRACT 
 
Mohs micrographic surgery (MMS) is considered the gold standard for treatment of high-
risk non-melanoma skin cancer. Postoperative bleeding is a complication that can lead to 
further complications including necrosis, infections, take-down of repairs, patient distress 
and unnecessary return visits including possibly to emergency rooms after hours. 
Tranexamic acid is an antifibrinolytic drug that prevents the breakdown of blood clots. 
The topical application of TXA has been shown to reduce intraoperative and 
postoperative bleeding in orthopedic, plastic, and maxillofacial surgeries.  It has also 
been used topically as a hemostatic agent in anterior epistaxis and superficial oral trauma. 
This study aims to determine the efficacy of topical TXA in preventing postoperative 
bleeding when used as an adjunct to wound care on granulating defects in the setting of 
MMS. 
 
2. OBJECTIVES 
 
To perform a prospective randomized controlled trial to determine the hemostatic effect 
of TXA soaked gauze (intervention) versus normal saline soaked gauze (control) when 
applied to granulating defects in the setting of Mohs micrographic surgery by collecting 
the following data: 
1. Rate of postoperative hemorrhagic complications. 
2. Types of postoperative hemorrhagic complications. 
 
3. BACKGROUND AND SIGNICANCE 
 
Mohs micrographic surgery (MMS) is considered the gold standard for treatment of high-
risk non-melanoma skin cancer.1 Bleeding complication rates and severity are very low in 
cutaneous surgery,2 but hematoma formation can lead to other complications such as 
infections, necrosis, and take-down of repairs such as grafts and flaps. The risk for 
bleeding complications is increased in some populations because anticoagulant and 
antiplatelet agents are typically not discontinued prior to Mohs surgery3. Intraoperatively, 
the modalities commonly used to decrease intraoperative and postoperative bleeding 
include the addition of adrenaline to local anesthetic, use of electrosurgery, suture 
ligation, and placement of topical hemostatic agents, such as absorbable hemostatic foam 
inserts.4 Postoperatively, pressure dressings are the standard preventative measure 
utilized in wound care to decrease risk of postoperative hemorrhage.5 
 
Antifibrinolytics decrease bleeding by preventing the natural breakdown of formed blood 
clots. Several different pharmaceutical formulations are available, including tranexamic 
acid (TXA). TXA is a synthetic lysine analogue that blocks binding sites of plasminogen 
to lysine, thus preventing plasminogen activation to plasmin and the subsequent 
enzymatic lysis of polymerized fibrin in blood clots.6 TXA can be administered 
intravenously, orally, subcutaneously, or topically, for the reduction of bleeding. 


PI: Nicholas Golda, MD 
 
IRB# 2025444 
 
 
V3; 5/20/21 
Although only the oral form of TXA is FDA approved to reduce bleeding in women with 
heavy menstrual cycles,7 it is administered intravenously in a wide range of surgical 
specialties including cardiothoracic8, obstetric,9 orthopedic10, and trauma11 to reduce risk 
of blood loss, and thus blood transfusions. Several studies have shown there is no 
increased risk of thrombotic events with this intervention6-9.  
 
The topical application of TXA has been shown to reduce intraoperative and 
postoperative bleeding in cardiothoracic12, orthopedic13, plastic14, and maxillofacial15 
surgeries, as well as for anterior epistaxis.16 A recent meta-analysis of 71 RTCs, mostly 
in the setting of orthopedic surgery, showed that topical TXA can reduce the incidence of 
blood transfusions by 70%.17 Systemic absorption and cytotoxicity to ex vivo skin is 
negligible under concentrations of 25mg/ml.18,19 There is no increased risk of 
thromboembolic events or myocardial infarction when TXA is applied topically.17 To our 
knowledge, there has been no study in which topical TXA has been added to wound care 
in the setting of MMS with the aim to reduce postoperative bleeding. 
 
4. STUDY PROCEDURES 
 
A. Study design 
I. 
Prospective randomized controlled trial 
II. 
Location:  University of Missouri Columbia Dermatologic Surgery Unit 
(Columbia, MO) 
III. 
Patients:  All adult (18 years or older) patients presenting for Mohs 
micrographic surgery (MMS) for the treatment of melanoma or 
nonmelanoma skin cancer (NMSC) with a wound that will be healing by 
granulation 
IV. 
Patients meeting inclusion criteria will be randomized into two arms once 
enrolled in the study and will be randomized using computerized 
randomization software. The study personnel will randomize patients on 
the day of surgery.  
a. One arm will serve as the control group and will receive 
normal saline soaked telfa pads to the wound bed upon 
completion of MMS.   
b. A second arm will receive TXA 25mg/ml soaked telfa pads to 
wound bed upon completion of MMS. This concentration is 
based on studies showing possible decrease in re-epithelization 
with chronic exposure to in vitro and ex vivo cutaneous wound 
bed models, as well as decreased viability of bovine and human 
cartilage, above this selected concentration.19-21 
V. 
Both solutions of the intervention and control are clear liquids that cannot 
be differentiated from one another. As such, the research staff will 
provide the surgeon with an unmarked sample cup of the either the saline 
solution or TXA solution, as selected by the randomization process for 
that individual patient. This will ensure that the surgeon, fellow, nursing 
staff, patient and family of patient are blinded to the intervention.  


PI: Nicholas Golda, MD 
 
IRB# 2025444 
 
 
V3; 5/20/21 
VI. 
TXA will be provided by IDS and stored on-site/in-clinic in a 
temperature controlled and temperature monitored refrigerator. The 
volume of TXA solution needed for the intervention, see below, will be 
diluted to 25mg/ml by research staff and provided to surgeon once patient 
is enrolled. 
VII. 
Volume of both intervention and control substance will be determined by 
size of defect. All defects will be considered circles for the purposes of 
calculating wound area.  The radius of the greatest dimension of the 
defect will be used to calculate the surface area using the formula, 
𝐴= 𝜋𝑟!. A volume of 1ml per 1cm2 will be dropped onto a Telfa pad 
that has been placed on the wound bed. A standard pressure dressing will 
be applied overtop. 
VIII. 
All patients will receive the same standardized post-operative wound care 
management instructions (see Appendix I) 
IX. 
Post-operative bleeding complications will be determined using the 
following data points (see Appendix II): 
a. Did patient call with concern for post-operative bleeding on the same day 
of surgery, or post-operative day 0 (POD0)? YES/NO 
b. Did patient call with concern for post-operative bleeding on POD1? 
YES/NO 
c. Did patient call with concern for post-operative bleeding on POD2? YES/ 
NO 
d. Did patient return to clinic within post-operative days 0-2 for evaluation 
of post-operative bleeding complication? YES/ NO 
e. Did patient receive postoperative intervention of any kind for 
hemorrhagic complication? YES/NO 
f. Type of intervention performed for bleeding complication.  
g. Perceived side-effects, if any, by patient due to study intervention. 
X. 
Study patients will be called 3 days after their surgical procedure to be 
asked the above data points in case a patient received outside care that 
was not disclosed to office or research staff. 
XI. 
Patients’ medical charts will be reviewed for and patients will also be 
asked to divulge the following medical history for demographic and sub 
analysis purposes (see AppendixIII): 
a. Age, sex, race 
b. Medical history including hypertension, coronary vascular 
disease, liver disease, renal disease 
c. Medications including anti-platelet agents and anti-coagulants 
B. Study duration and number of study visits required of research participants. 
I. 
Duration sufficient to enroll 124 patients (62 per treatment arm).  No 
additional patient visits will be required beyond the visit normally required 
for their procedure and/or suture removal. 
II. 
The initial visit for this study will take place after already scheduled Mohs 
micrographic surgery which will take no longer than one additional hour 
during the surgical visit. 


PI: Nicholas Golda, MD 
 
IRB# 2025444 
 
 
V3; 5/20/21 
III. 
Participation includes a total of three days, specifically postoperative days 
0-2. 
IV. 
 
C. Blinding, including justification for blinding or not blinding the trial, if 
applicable. 
I. 
Double-blinded trial in which patients and surgeons will be masked to 
which treatment arm participants are assigned  
D. Justification of why participants will not receive routine care or will have current 
therapy stopped. 
I. 
Care will be identical in both arms except for addition of topical 
application of TXA vs normal saline soaked gauze to wound bed at 
completion of MMS.  
E. Justification for inclusion of a placebo or non-treatment group. 
I. 
There will be a control group of patients who do not receive the 
intervention, topical TXA, and instead will receive topical application of 
normal saline in order to provide a blinded comparison to the intervention 
arm. This will prevent unconscious bias from affecting patient and 
surgeon perception of postoperative bleeding complications. 
F. Definition of treatment failure or participant removal criteria. 
I. 
Patient will be removed from the study if  
i. Patient removes bandage and cleans wound within 24hrs 
ii. Patient seeks postoperative care from outside institution within 
study timeframe (POD0-2), thus not allowing researchers to 
evaluate postoperative complication. This will be elucidated with a 
phone call three days after surgery. 
II. 
Patients may also voluntarily leave the study. Only patients who complete 
all steps of the study will be included in data analysis, but the number of 
enrollees who do not complete the study will be tabulated to track if there 
is a significant difference between the groups. 
G. Description of what happens to participants receiving therapy when study ends or 
if a participant’s participation in the study ends prematurely. 
I. 
There will be no effect on the patient. 
 
5. INCLUSION/ EXCLUSION CRITERIA 
 
A. Adult (18 years or older) patients being treated with Mohs micrographic surgery 
will be included in this study. 
B. Surgical procedure must include one of the following: 
a. Any defect being healed by granulation  
i. Including periocular defects22 
ii. Including defects with fenestrated cartilage20,21 
iii. Including skin graft donor sites left to heal by granulation 
C. Patients must not 


PI: Nicholas Golda, MD 
 
IRB# 2025444 
 
 
V3; 5/20/21 
a. be pregnant or breastfeeding 
i. urine qualitative pregnancy test will be obtained in-office, prior to 
surgery, from women of childbearing potential 
ii. pregnancy test not required on post-menopausal women or women 
with history of tubal ligation, ablative uterine procedure or 
salpingo/oophor/hyster-ectomy 
b. Have a known allergic reaction or sensitivity to TXA 
c. Have an international normalized ratio (INR) out of therapeutic range if on 
warfarin; all patients on warfarin will be tested within one week of surgery 
i. INR level will be obtained within 1 week prior to time of 
intervention 
ii. therapeutic range INR 2.0-3.0 
iii. if high-risk prosthetic heart valve, therapeutic range INR 2.5 – 3.5 
6. DRUGS/ SUBSTANCES/ DEVICES 
A. Active intervention group: application of TXA soaked gauze on open wound 
defect, held in place by standard postoperative pressure bandage 
B. Control group: Identically placed sterile normal saline soaked gauze, held in place 
by standard postoperative pressure bandage 
7. STUDY STATISTICS 
A. Primary outcome variable.  
I. 
Determination of effects of topical TXA on postoperative hemorrhagic 
complications and need for additional visits for care related to bleeding 
complications within the first 2 days following Mohs surgery with a 
wound allowed to heal by granulation 
B. Secondary outcome variables. 
I. 
Determination of possible adverse effects, if any, that are different 
between the intervention and control arms. 
C. Statistical plan including sample size justification and interim data analysis 
I. 
The statistical analysis will be performed by the University of Missouri 
biostatistics group.  The sample size was calculated using a power analysis 
with the alpha set to 0.05 and the power set to 80%.  Dichotomous 
variables were assessed with an anticipated change of bleeding of 10% in 
the intervention group and 30% in the control group based on prior clinical 
experience.  No interim data analysis is planned.  
II. 
Data will be analyzed on an intention to treat basis.   
D. Early stopping rules. 
I. 
Study will end early if severe or high rate of adverse events occur. 
 
8. RISKS 
A. Medical risks, listing all procedures, their major and minor risks and expected 
frequency. 


PI: Nicholas Golda, MD 
 
IRB# 2025444 
 
 
V3; 5/20/21 
I. 
Topical TXA application 
a. potential local allergic reaction 
B. Steps taken to minimize the risks. 
I. 
Plan for reporting unanticipated problems or study deviations. 
a. Will report all deviations and problems to IRB. 
II. 
Legal risk such as the risks that would be associated with breach of 
confidentiality. 
a. Participants will be assigned a study number, which will have no 
identifiable information. Key to match study number with patient 
will be located and protected on encryption secured software with 
access only available to research team. Hard copy will be located 
in research office in locked cabinet with key only available to 
research team. 
III. 
Financial risks to the participants. 
a. In the case of adverse events related to study, participants may 
incur medical fees associated with treatment of the adverse events. 
 
9. BENEFITS 
A. Description of the probable benefits for the participant and for society. 
I. 
Patients may have reduced post-operative bleeding complications and 
improved overall surgical experience if in the intervention arm. 
II. 
If this intervention is helpful, then the intervention may serve as an 
additional hemostatic wound care option in cutaneous surgery to prevent 
postoperative bleeding complications and the costs and angst associated 
with such complications 
 
10. COSTS 
A. An application for funding will be made for the MU Department of Dermatology 
Dyer research fund and from the MU MSDO Procedural Fellowship Endowment. 
B. Participants will not incur any costs during this study, outside of standard of care 
procedural costs billed to their insurance, including INR or pregnancy testing as 
indicated. Patients will not be billed for intervention or placebo drug. 
 
 
 


PI: Nicholas Golda, MD 
 
IRB# 2025444 
 
 
V3; 5/20/21 
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PI: Nicholas Golda, MD 
 
IRB# 2025444 
 
 
V3; 5/20/21 
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