Tranexamic Acid to Improve Same-day Discharge Rates After Holmium Laser Enucleation of the Prostate (HoLEP)
Phase: PHASE4
Conditions: Kidney Calculi, Urologic Diseases, Benign Prostatic Hypertrophy
Sponsor: Northwestern University

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NCT05082142 
 
Tranexamic Acid to Improve Same-day Discharge Rates After Holmium Laser 
Enucleation of the Prostate (HoLEP) 
 
10/29/2021 
 
Protocol 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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PROTOCOL TITLE: Tranexamic acid to improve same-day discharge rates after Holmium 
Laser Enucleation of the Prostate (HoLEP) 
 
 
PRINCIPAL INVESTIGATOR: 
Amy Krambeck, MD 
Department of Urology 
amy.krambeck@nm.org 
 
VERSION DATE: 
10.29.2021 
 
  
STUDY SUMMARY: 
 
Investigational Agent(s)  
(Drugs or Devices) 
Tranexamic acid 
IND / IDE / HDE #   
Indicate 
Special Population(s) 
Children  
 Children who are wards of the state  
 Adults Unable to Consent   
 Cognitively Impaired Adults  
 Neonates of Uncertain Viability  
 Pregnant Women  
 Prisoners (or other detained/paroled individuals)  
 Students/Employees  
Sample Size 110 
Funding Source Department of Urology 
Indicate the type of consent 
to be obtained 
Written  
Verbal/Waiver of Documentation of Informed Consent 
Waiver of HIPAA Authorization  
Waiver/Alteration of Consent Process   
Site 
 Lead Site ( For A Multiple Site Research Study) 
 Data Coordinating Center (DCC) 
Research Related 
Radiation Exposure 
Yes  
 No  
DSMB / DMC / IDMC 
Yes  
No 
 
OBJECTIVES: 
 
 
This study is designed to assess if there is a significant difference in same day discharge 
rates after Holmium Laser Enucleation of the Prostate (HoLEP). We attempt to perform HoLEP 
as a same-day discharge (SDD) procedure, but at NM, our SDD rate is currently approximately 
60%.  The limiting factor in SDD is hematuria. Tranexamic acid (TXA) is a clot promoting drug 
that is commonly used by orthopedic, cardiac and obstetric surgeons to prevent bleeding. Our 

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primary outcome will be to assess if there is a difference in SDD rates in those who receive TXA 
vs. those who do not. 
 
 
Secondary outcomes will assess bleeding complications (defined as unplanned ED 
visit/clinicvisit/procedure/admission related to bleeding, clot retention, clot evacuation, need for 
perioperative transfusion) between patients who receive TXA vs. those do not.  We will also 
assess differences in perioperative complications associated with TXA including but not limited 
to: deep venous thrombosis, pulmonary embolism, cerebrovascular events, between the 
groups.  We will also assess for the duration of postoperative hematuria between groups.  
Additionally, we will assess for differences in operative times between the groups. 
 
We anticipate that there may be up to a 25% increase in SDD rates in those who receive TXA 
vs. those who do not. 
 
BACKGROUND: 
Holmium Laser Enucleation of the Prostate (HoLEP) is a size-independent treatment option for 
bening prostate hypertrophy (BPH) as recommended by the American Urological Association 
(AUA) Guidelines.1 Furthermore, HoLEP is one of the few surgical options that is recommended 
by the AUA for patients on active anticoagulation given its superior hemostatic properties.1 Dr. 
Krambeck’s research team has previously shown that same-day catheter removal and same-
day discharge (SDD) was successful in approximately 87% of patients.2 This study was 
performed in a limited cohort of 207 patients.  Dr. Krambeck was recently recruited to 
Northwestern Medicine to introduce HoLEP to Chicago. Our current SDD rate is approximately 
60%.  Factors limiting discharge are primarily related to the degree of hematuria and patient 
anxiety. 
Tranexamic Acid (TXA) is an indirect fibrinolytic inhibitor and was discovered in the early 
1960s.3  Although it was initially only used in women with heavy menstrual blood loss and those 
with hereditary bleeding disorders, it is now widely used in trauma situations and orthopedic, 
cardiac, otolaryngologic, and obstetric surgeries as it is cheap, safe, and effective.3 Oral, IV, 
topical and combined methods of TXA administration also reduced blood loss and risk of 
transfusion compared to placebo for patients undergoing total hip arthroplasty.4 TXA is safe, but 
high doses of TXA (80-100 mg/kg) or TXA use in those with poor renal function have been 
associated with an increased risk of seizures.5  While there is no clear evidence of increased 
risk of thromboembolic events6, it should be used cautiously in those with a history of embolic 
events, those on hormonal contraceptives 7 
 
Use of TXA in Urologic literature has been limited. One prospective, randomized 
controlled trial studied the use of TXA in 40 men undergoing transurethral resection of the 
prostate (TURP).8 The authors found that TXA resulted in significantly less postoperative serum 
hemoglobin drop, less hemoglobin loss per gram of resected tissue, shorter OR time, and more 
resected tissue.8 In another prospective, randomized controlled trial, the authors randomized 
136 men undergoing TURP to receiving TXA or not.9 The authors found TXA resulted in 
reduced operative blood loss, the amount of blood loss per gram of resected tissue, and shorter 
OR time.  Interestingly, TXA did not decrease length of stay or catheter duration.9  In one 
systematic review analyzing the effects of TXA after transurethral resection of the prostate, the 
authors included nine studies in their meta-analysis and found that TXA reduced intraoperative 
estimated blood loss as well as the transfusion rate.10 The use of TXA in percutaneous 
nephrolithotomy (PCNL) has also been studied. A randomized, double-blinded, placebo-
controlled trial enrolled 192 patients with Guy’s stone scores III-IV.  Patients were given 1g of IV 
TXA vs. placebo at time of anesthetic induction.  The authors found that TXA administration 
during PCNL resulted in reduced blood transfusion rate, and higher stone free rates in the 
immediate postoperative period and at 3 months.11 

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Although HoLEP is one of the few surgical options recommended by the AUA for 
patients at high risk of bleeding due to its excellent hemostatic properties, for patients 
undergoing same-day discharge, hematuria is often the rate limiting factor. Currently, no studies 
have examined the use of TXA during HoLEP.  Therefore, we would like to study if the use of 
TXA during HoLEP will increase our SDD rates. 
 
STUDY ENDPOINTS: 
Primary: 
 
1) Difference in same-day discharge and same-day catheter removal rates  
 
     Secondary: 
2) Difference in medical events: defined as unplanned ED visit/clinic 
visit/procedure/admission related to bleeding, clot retention, clot evacuation, need for 
perioperative transfusion 
3) Duration of postoperative hematuria 
4) Difference in operative, enucleation and morcellation times 
5) Adverse events related to TXA (thrombotic events (DVT, PE, stroke), seizures,   
 
PROCEDURES INVOLVED: 
Visit 1 – Screening (Day -45 – Day 0) 
i. Patients will complete:  
1) Patient Informed Consent Form,  
2) HIPAA form,  
ii. Investigative site will complete: patient demographics, medical history, 
Inclusion/Exclusion Criteria 
iii. Randomization and instructions to patients on whether or not to receive 
TXA 
Visit 2 – HoLEP (Day 0) 
iv. Inclusion/Exclusion Criteria to reconfirm eligibility (only if Screening and 
HoLEP are not on the same day) 
v. Adverse Events secondary to TXA 
Catheter Removal (Day 0 or 1) 
Assessment of same day discharge and catheter removal rates 
Week 1 through resolution of hematuria 
The patient will receive a weekly computed generated text from Twilio 
(secure software integrated to REDCap) asking them to report their 
hematuria and dysuria after the procedure.  It will also ask if they have had 
any unplanned visits or interventions.  This will continue until 12 week post 
HoLEP survey 
Visit 3 – One month follow-up (Day 30) 
If patients have already reported resolution of hematuria, they will receive 
an additional questionnaire 30 days postoperatively to assess for 
bleeding complications and symptoms. 
Visit 4 – Follow-up (12 weeks Post HoLEP) 
vi. Patient will be assessed for BPH symptom related questionnaires in 
addition to urinary parameters.  Will also confirm if there were or were not 
bleeding or other complications in first 90 days postoperatively. 
Early Withdrawal Patients: The investigator will make reasonable attempts to 
ensure all enrolled patients complete the study.   
**If the patient is unable to complete the questionnaires by text, they will be 
contacted by phone call for questionnaire completion. 

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The HoLEP procedure is performed in a similar fashion by all surgeons with similar 
postoperative care plans.  Duration of postoperative catheterization is determined by the 
treating surgeon, with respect to time of surgical case completion, need for inpatient 
observation, and patient preference.  The portions of the case will not be altered regardless of 
patient being on anticoagulation or not, however the surgeon will not be blinded to the patient’s 
status of anticoagulation therapy, as this knowledge would be paramount in postoperative 
management if there were complications. 
 
DATA AND SPECIMEN BANKING 
Data will be collected and stored electronically in REDCap.  Quality assurance steps will include 
testing of database including any potential data calculated by command functions within 
REDCap (ex: age of patient at time of surgery calculated by using patient’s date of birth and 
date of surgery) by study team prior to moving to production mode.  The following quality control 
methods will be used: 1) single entry of data with random checks of accuracy, and 2) extraction 
and cleaning of data on a monthly basis that will be used for analysis every 3 months until 
completion of enrollment. 
 
Data will be accessible to only authorized members of the study team. Any presentations on the 
study or published findings will use only de-identified data.  
 
Data will be stored for 7 years after the end of the study. After this period, electronic data will be 
deleted.  
 
SHARING RESULTS WITH PARTICIPANTS 
Study results will not be shared with participants. 
 
INCLUSION AND EXCLUSION CRITERIA 
Inclusion Criteria 
• 
Males 18 -89 undergoing HoLEP 
• 
Willing to sign the Informed Consent Form  
• 
Able to read, understand, and complete patient questionnaires, pain texts, and 
medication diary. 
 
Exclusion Criteria 
• 
Allergy or hypersensitivity to TXA, history of acute venous or arterial thrombosis, 
intrinsic risk for thrombosis or thromboembolism, history of thromboembolic disease, 
hereditary thrombophilia, use of hormonal agents 
• 
Patients having a concurrent ureteroscopy +/- laser lithotripsy, percutaneous 
nephrolithotomy, or non-urologic surgery at the time of their HoLEP 
• 
Anticipated need for perineal urethrostomy at the time of HoLEP 
• 
Patient not undergoing catheter removal and voiding trial at Northwestern Memorial 
Hospital  
 
 
PARTICIPANT POPULATION(S) 
Accrual 
Number: 
Category/Group: 
(Adults/Children 
Special/Vulnerable 
Populations) 
Consented: 
Maximum Number to be 
Consented or 
Reviewed/Collected/Screened 
Enrolled: 
Number to Complete 
the Study or Needed 

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to Address the 
Research Question 
Local 
0 
110 
110 
 
 
 
Study-wide 
0 
110 
 
 
 
 
Total: 
0 
110 
110 
 
 
RECRUITMENT METHODS 
Enrollment into the study will be performed by a qualified research coordinator.   
After the patient completes their pre-surgical enrollment paperwork in the clinic, they will then be 
met in a private room away from the treating physicians by a qualified research coordinator who 
will discuss their potential enrollment and complete any research paperwork.  Some patients 
may be approached via telephone with virtual consent. 
 
Therefore, the initiation of enrollment will begin at the time of the office consultation visit. The 
patient will remain enrolled until she/he has completed the post-procedure follow up clinic/virtual 
visit at week 12. Data will not be collected beyond when the patient is seen at the postoperative 
clinic visit.  If the patient is unable to have a physical or virtual visit, a text follow-up will be 
performed. 
After consenting, patients will be randomized to one of two groups.  
 
Group 1 (control):  Receive intraoperative 1g TXA 
Group 2 (experimental):  No TXA 
 
Randomization to Group 1 or Group 2 will be allocated through REDCap.12 The stratified 
randomization list will be created and provided by the study statistician before the start of patient 
recruitment. 
 
COMPENSATION FOR PARTICIPATION IN RESEARCH ACTIVITIES 
Patients will not be compensated for participating in this research.  
 
WITHDRAWAL OF PARTICIPANTS 
If a subject wishes to withdraw from the study, he/she may do so by verbal request to the 
research team.  A subject may be withdrawn from the study by a physician-investigator if 
determined to be in the subject’s best interest for medical reasons. 
 
 
RISKS TO PARTICIPANTS 
The risks in this study are no greater than the risks incurred during a HoLEP.  AUA and EAU 
guidelines support HoLEP as a size independent treatment option for BPH. 
 
Common side effects of TXA are nausea, vomiting, diarrhea, and muscle pain. 
 

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POTENTIAL BENEFITS TO PARTICIPANTS 
Patients in the TXA arm may have higher rates of success with same day discharge and same 
day catheter removal. 
 
DATA MANAGEMENT AND CONFIDENTIALITY 
Data will be collected and stored electronically in REDCap.  Quality assurance steps will include 
testing of database including any potential data calculated by command functions within 
REDCap (ex: age of patient at time of surgery calculated by using patient’s date of birth and 
date of surgery) by study team prior to moving to production mode.  The following quality control 
methods will be used: 1) single entry of data with random checks of accuracy, and 2) extraction 
and cleaning of data on a monthly basis that will be used for analysis every 3 months until 
completion of enrollment. 
 
PROVISIONS TO PROTECT THE PRIVACY INTERESTS OF PARTICIPANTS 
Data will be collected and stored electronically in REDCap and will only be accessible to 
members of the study team.  
Data resulting from this study will not be linked to subjects. Subjects will not be referred to by 
name of initial in any publications.  
 
CONSENT PROCESS 
Enrollment into the study will be performed by a qualified research coordinator.   
 
After the patient completes their pre-surgical enrollment paperwork in the clinic, they will then be 
met in a private room away from the treating physicians by a qualified research coordinator who 
will discuss their potential enrollment and complete any research paperwork.  Some patients 
may be approached via telephone with virtual consent. 
 
PROTECTED HEALTH INFORMATION (PHI AND HIPAA) 
HIPAA authorization will be obtained as part of the consent. PHI from medical records and 
information collected from research and tumor samples will be protected by using coded subject 
numbers. The coded identifiers will be stored on a password protected spreadsheet stored on 
the FSM Urology server. 
 
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Parsons JK BM, Dahm P, Gahndi MC, Kaplan SA, Kohler TS Lerner LB, Roehrborn CG, 
Stoffel JT, Welliver C, Wilt TJ, McVary KT. Benign Prostatic Hyperplasia: Surgical 
Management of Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms AUA Guidelines. 
2019; 
2. 
Agarwal DK, Large T, Tong Y, et al. Same Day Discharge is a Successful Approach for 
the Majority of Patients Undergoing Holmium Laser Enucleation of the Prostate. Eur Urol 
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Tengborn L, Blomback M, Berntorp E. Tranexamic acid--an old drug still going strong 
and making a revival. Thromb Res. Feb 2015;135(2):231-42. doi:10.1016/j.thromres.2014.11.012 
4. 
Fillingham YA, Ramkumar DB, Jevsevar DS, et al. The Efficacy of Tranexamic Acid in 
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7. 
Ng W JA, Wasowicz M. Tranexamic acid: a clinical review. Anestezjologia Intensywna 
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8. 
Kumsar S DA, Toksoz S, Saglam HS Adsan O. Tranexamic acid decreases blood loss 
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9. 
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Batagello CA, Vicentini FC, Monga M, et al. Tranexamic acid in patients with complex 
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