## Protocol Section
### Identification Module
**NCT ID:** NCT06419075

**Acronym:** TEXAS

**Brief Title:** Tranexamic Acid in Vaginal Reconstructive Surgery

**Official Title:** Local Infiltration of TranExamic Acid in Surgical Management of Pelvic Organ Prolapse: a Pilot Randomized Clinical Trial

#### Organization Study ID Info
**ID:** 23-0273
#### Organization
**Class:** OTHER
**Full Name:** The University of Texas Medical Branch, Galveston
### Status Module
#### Completion Date
**Date:** 2026-03-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-17

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-13

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-17
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-08
**Study First Submit QC Date:** 2024-05-13
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** MOUNT SINAI HOSPITAL

**Class:** OTHER

**Name:** The University of Texas Health Science Center, Houston

#### Lead Sponsor

**Class:** OTHER

**Name:** The University of Texas Medical Branch, Galveston

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Tranexamic acid (TXA) has been demonstrated to reduce blood loss in trauma, orthopedic, cardiac, and plastic surgeries in numerous well-designed and adequately powered studies. As a result of this evidence for benefit, TXA is routinely used to reduce blood loss during these surgeries. There are no studies regarding the use of TXA in urogynecology. The investigators seek to explore the effect and safety of local infiltration of TXA in vaginal reconstructive surgery.

**Detailed Description:** This is a multicenter, double blinded, pilot randomized clinical trial that will be conducted at UTMB Health, and other participating sites. Each participating site will obtain IRB approval. Women with symptomatic, stage II to IV Pelvic organ prolapse (POP) who plan colpocleisis will be approached to participate. Using the study protocol inclusion and exclusion criteria, patient's eligibility will be determined. All eligible subjects will provide the written informed consent before any research data is collected. All screening assessment will be completed at a preoperative, in-person, clinic visit, and within 60 days of surgery. The subject will then undergo randomization to the local TXA, or Vasopressin, or NS group with the total sample size of 36 female subjects (12 per group). Concomitant procedures for POP or urinary incontinence are permitted and will be based upon the operating surgeons' standard clinical practice and best clinical judgement. The anesthesia team is responsible for preparing the study agents, monitoring intraoperative cardiovascular parameters (blood pressure and heart rate) as well as adverse events, and determining the blood transfusion if needed. Subsequently, the subject will have postoperative follow up at 2 weeks and 6 weeks

### Conditions Module

**Conditions:**

- Pelvic Organ Prolapse

**Keywords:**

- Tranexamic Acid

- Colpocleisis

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** The enrolled subjects will be randomized into one of the 3 arms including tranexamic acid (2 mg/dL), vasopressin (0.1 U/dL), and normal saline.

##### Masking Info

**Masking:** QUADRUPLE

**Masking Description:** The attending anesthesiologist will receive the randomized assignment from the lead research team at UTMB and prepare the diluted study agents. The OR staff, attending surgeon, and learners including fellows and residents are blinded.

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 36

**Type:** ESTIMATED

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Local infiltration of 50 cc NaCl 0.9% into the vaginal submucosa during colpocleisis dissection

**Intervention Names:**

- Other: NaCl 0.9%

**Label:** Normal Saline (NaCl 0.9%)

**Type:** PLACEBO_COMPARATOR

#### Arm Group 2

**Description:** Local infiltration of 50 cc Tranexamic Acid (2 mg/dL) into the vaginal submucosa during colpocleisis dissection

**Intervention Names:**

- Drug: Tranexamic acid

**Label:** Tranexamic Acid (2 mg/dL)

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** Local infiltration of 50 cc Vasopressin (0.1 U/dL) into the vaginal submucosa during colpocleisis dissection

**Intervention Names:**

- Drug: Vasopressin

**Label:** Vasopressin (0.1 U/dL)

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Tranexamic Acid (2 mg/dL)

**Description:** The intervention of 50 cc TXA (2 mg/mL) local infiltration is determined after carefully reviewing the literature. Scarafoni et al. recommends that the local TXA should not exceed at a concentration of 5-10 mg/mL to avoid cytotoxicity that may affect the wound re-epithelialization (22). In a prospective study on facelift bleeding, Kochuba et al. demonstrates that local TXA (1-2 mg/mL) with total 100 mg and 200 mg TXA safely and effectively decreased bleeding, operating room time, and drain output compared with traditional local anesthetic technique (14). Fathimani et all reports the local use of modified tumescent anesthesia solution with low TXA concentration (2 mg/dL) and total average dosage of TXA ranging 120-1000 mg is safe and promising in achieving less ecchymosis, edema, and seroma in common facial cosmetic surgical procedures (31). With a total dosage of 100 mg TXA and a volume of 50 cc injection, the concentration is calculated to be 2 mg/dL.

**Name:** Tranexamic acid

**Other Names:**

- Tranexamic acid (CYKLOKAPRON) (Pfizer, New York, NY).

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Vasopressin (0.1 U/dL)

**Description:** The intervention of 50 cc Vasopressin (0.1U/mL) local infiltration is determined from several systematic reviews. Hafidh et al. shows that injection of diluted Vasopressin (3.6 to 10 units) with various concentration during hysterectomy significantly reduces the intraoperative blood loss when compared to placebo, and without increasing the hazard of cardiovascular toxicities. Cui et al. reports similar results, but including other vaginal surgeries. The common preparation for dilute Vasopressin is 0.1 U/mL or 1.0 U/mL from a 1cc vial of 20 U/mL Vasopressin. The advantage of 0.1 U/mL concentration is to avoid a relatively large bolus of concentrated 1.0 U/mL Vasopressin injected intravascularly by accident. A cumulative total dose of 4 to 6 units of Vasopressin administered in a dilute solution is proposed to be an upper limit. Therefore, the cumulative total dose of 5 units Vasopressin from 50 cc (0.1U/mL) is in the safe therapeutic range.

**Name:** Vasopressin

**Other Names:**

- Vasopressin (Vasostrict) (Par Pharmaceutical, Chestnut Ridge, NY).

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Normal Saline (NaCl 0.9%)

**Description:** The intervention of 50 cc NaCl 0.9% local infiltration serves a placebo control.

**Name:** NaCl 0.9%

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** Compare intraoperative QBL during colpocleisis with the local infiltration of Tranexamic acid to the current standard of care, vasopressin or normal saline.

**Measure:** Intraoperative quantitative blood loss QBL (mL)

**Time Frame:** Intraoperatively

#### Secondary Outcomes

**Description:** Compare the colpocleisis operative time between Tranexamic acid, vasopressin or normal saline groups

**Measure:** Colpocleisis operative time (min)

**Time Frame:** Intraoperatively

**Description:** Evaluate the effect blood pressures at 1, 5, and 10 mins after the local infiltration of Tranexamic acid, vasopressin and NS into the vaginal mucosa.

**Measure:** Intraoperative blood pressure (mmHg)

**Time Frame:** Intraoperatively

**Description:** Evaluate the effect on heart rate at 1, 5, and 10 mins after the local infiltration of Tranexamic acid, vasopressin and NS into the vaginal mucosa.

**Measure:** Intraoperative hear rate (beats/min)

**Time Frame:** Intraoperatively

**Description:** Assess postoperative complications following colpocleisis using the Clavien-Dindo Classification (CDC) categories

**Measure:** Postoperative complications

**Time Frame:** 2 weeks and 6 weeks postoperatively

**Description:** Quantify the need for blood-product transfusion and the volume administered as a direct result of colpocleisis, either intraoperative or postoperative

**Measure:** Rate of transfusion

**Time Frame:** Intraoperatively and 2 weeks postoperatively

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Females who are menopausal at the time of consent
2. Able to understand and read English
3. Able and willing to provide written informed consent
4. Able to comply with the follow-up study protocol, per clinician judgment
5. Symptomatic POP (bulge or pressure) evidenced with vaginal prolapse with POP-Q measurement consistent with Stage II-IV
6. LeFort or complete colpocleisis as desired surgical approach to correct POP with and without other concomitant procedures
7. History of abdominal or vaginal surgery for POP
8. American Society of Anesthesiologists (ASA) physical status I or II

Exclusion Criteria:

1. Texas Department of Criminal Justice prisoners
2. Refusal of blood products (e.g, Jehovah's witnesses)
3. ASA physical status III or IV
4. Known allergy or hypersensitivity to TXA or any of the ingredients
5. Subarachnoid hemorrhage
6. Active intravascular clotting, thromboembolic disease (cerebral thrombosis, deep vein thrombosis, or pulmonary embolism)
7. Epilepsy, seizure disorders requiring anti-epileptic medication(s)
8. Acquired impaired color vision (color blindness, retinal involvement)
9. Intrinsic risk of thrombosis or thromboembolism (hypercoagulopathy, thrombogenic cardiac rhythm disease, thrombogenic valvular disease)
10. History of severe liver disease
11. Known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol
12. History of cardiac diseases (decompensated congestive heart failure CHF, recent coronary artery disease CAD within 30 days, recent myocardial infarction MI within 30 days)
13. History of reversible nephrogenic diabetes insipidus
14. History of primary pelvic organ cancer (uterine, ovarian, endometrial, cervical, bladder) or any cancer that is metastatic to the pelvis
15. Prior or current pelvic radiation, or chemotherapy.
16. Females who desires to have vaginal sexual intercourse after the surgery

**Healthy Volunteers:** True

**Maximum Age:** 100 Years

**Minimum Age:** 50 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** trhdo@utmb.edu

**Name:** Trieu H Do, MD

**Phone:** 8326327964

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Galveston

**Country:** United States

**Facility:** University of Texas Medical Branch Galveston

**State:** Texas

**Zip:** 77554

#### Overall Officials

**Official 1:**

**Affiliation:** University of Texas Medical Branch Galveston

**Name:** Gokhan Kilic, MD

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** Mount Sinai Hospital & Medical Center

**Name:** Ann Tran, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Description:** We are not planning to make individual participant data (IPD) available to other researchers.

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Smith FJ, Holman CD, Moorin RE, Tsokos N. Lifetime risk of undergoing surgery for pelvic organ prolapse. Obstet Gynecol. 2010 Nov;116(5):1096-100. doi: 10.1097/AOG.0b013e3181f73729.

**PMID:** 20966694

**Citation:** Cheng W, Bu C, Hong F, Zhong X, Jin C, Yang X, Sun X, Wang J. Perioperative hemorrhagic complications in pelvic floor reconstructive surgery. Int Urogynecol J. 2019 Jul;30(7):1141-1146. doi: 10.1007/s00192-018-3667-6. Epub 2018 May 21.

**PMID:** 29785542

**Citation:** Lambrou NC, Buller JL, Thompson JR, Cundiff GW, Chou B, Montz FJ. Prevalence of perioperative complications among women undergoing reconstructive pelvic surgery. Am J Obstet Gynecol. 2000 Dec;183(6):1355-8; discussion 1359-60. doi: 10.1067/mob.2000.110911.

**PMID:** 11120496

**Citation:** Johnson DJ, Scott AV, Barodka VM, Park S, Wasey JO, Ness PM, Gniadek T, Frank SM. Morbidity and Mortality after High-dose Transfusion. Anesthesiology. 2016 Feb;124(2):387-95. doi: 10.1097/ALN.0000000000000945.

**PMID:** 26569167

**Citation:** Ghadimi K, Levy JH, Welsby IJ. Perioperative management of the bleeding patient. Br J Anaesth. 2016 Dec;117(suppl 3):iii18-iii30. doi: 10.1093/bja/aew358.

**PMID:** 27940453

**Citation:** Cui Y, Chen I, Chernoff A, Clancy A. Effectiveness of prophylactic pharmacological hemostatic agents for reduction of blood loss at vaginal surgery: a systematic review and meta-analysis. Int Urogynecol J. 2023 Dec;34(12):2945-2957. doi: 10.1007/s00192-023-05614-1. Epub 2023 Aug 16.

**PMID:** 37584705

**Citation:** Hafidh B, Latifah HM, Gari A, Alshahrani MS, AlSghan R, Alkhamis WH, Allam HS, AlRasheed MA, Bakhsh H, Abu-Zaid A, Baradwan S. Vasopressin to Control Blood Loss during Hysterectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Minim Invasive Gynecol. 2022 Mar;29(3):355-364.e2. doi: 10.1016/j.jmig.2021.10.003. Epub 2021 Oct 12.

**PMID:** 34648933

**Citation:** Willis-Gray MG, Husk KE, Brueseke TJ, Connolly A, Geller EJ. Lidocaine Use in Vaginal Surgery and Risk of Toxicity. Female Pelvic Med Reconstr Surg. 2020 Sep;26(9):546-549. doi: 10.1097/SPV.0000000000000622.

**PMID:** 30346319

**Citation:** Zakhari A, Sanders AP, Solnik MJ. Tranexamic acid in gynecologic surgery. Curr Med Res Opin. 2020 Mar;36(3):513-520. doi: 10.1080/03007995.2019.1708533. Epub 2020 Jan 6.

**PMID:** 31865770

**Citation:** Luetzenberg FS, Lyford-Pike S. Modern use of tranexamic acid in facial plastic surgery. Curr Opin Otolaryngol Head Neck Surg. 2023 Aug 1;31(4):219-223. doi: 10.1097/MOO.0000000000000886. Epub 2023 Apr 13.

**PMID:** 37052603

**Citation:** Breau RH, Kokolo MB, Punjani N, Cagiannos I, Beck A, Niznick N, Buenaventura C, Cowan J, Knoll G, Momoli F, Morash C, Ruzicka M, Schachkina S, Tinmouth A, Xie HY, Fergusson DA. The effects of lysine analogs during pelvic surgery: a systematic review and meta-analysis. Transfus Med Rev. 2014 Jul;28(3):145-55. doi: 10.1016/j.tmrv.2014.05.002. Epub 2014 May 18.

**PMID:** 24958068

**Citation:** El Minawi HM, Kadry HM, El-Essawy NM, El Saadany ZA, Nouh OM. The effect of tranexamic acid on blood loss in liposuction: a randomized controlled study. Eur J Plast Surg. 2023;46(2):227-237. doi: 10.1007/s00238-022-01995-6. Epub 2022 Oct 22.

**PMID:** 36311870

**Citation:** Couto RA, Charafeddine A, Sinclair NR, Nayak LM, Zins JE. Local Infiltration of Tranexamic Acid With Local Anesthetic Reduces Intraoperative Facelift Bleeding: A Preliminary Report. Aesthet Surg J. 2020 May 16;40(6):587-593. doi: 10.1093/asj/sjz232.

**PMID:** 31504134

**Citation:** Kochuba AL, Coombs DM, Kwiecien GJ, Sinclair NR, Zins JE. Prospective Study Assessing the Effect of Local Infiltration of Tranexamic Acid on Facelift Bleeding. Aesthet Surg J. 2021 Mar 12;41(4):391-397. doi: 10.1093/asj/sjaa198.

**PMID:** 32644111

**Citation:** Coombs DM, Kwiecien GJ, Sinclair NR, Jin A, Zins JE. Local Infiltration of Tranexamic Acid During Facelift Improves Operating Room Efficiency: A Matched Patient Study. Aesthet Surg J. 2022 Aug 24;42(9):971-977. doi: 10.1093/asj/sjac067.

**PMID:** 35350068

**Citation:** Ausen K, Fossmark R, Spigset O, Pleym H. Safety and Efficacy of Local Tranexamic Acid for the Prevention of Surgical Bleeding in Soft-Tissue Surgery: A Review of the Literature and Recommendations for Plastic Surgery. Plast Reconstr Surg. 2022 Mar 1;149(3):774-787. doi: 10.1097/PRS.0000000000008884.

**PMID:** 35196701

**Citation:** Rohrich RJ, Cho MJ. The Role of Tranexamic Acid in Plastic Surgery: Review and Technical Considerations. Plast Reconstr Surg. 2018 Feb;141(2):507-515. doi: 10.1097/PRS.0000000000003926.

**PMID:** 28938364

**Citation:** Buchsbaum GM, Lee TG. Vaginal Obliterative Procedures for Pelvic Organ Prolapse: A Systematic Review. Obstet Gynecol Surv. 2017 Mar;72(3):175-183. doi: 10.1097/OGX.0000000000000406.

**PMID:** 28304415

**Citation:** Grzybowska ME, Futyma K, Kusiak A, Wydra DG. Colpocleisis as an obliterative surgery for pelvic organ prolapse: is it still a viable option in the twenty-first century? Narrative review. Int Urogynecol J. 2022 Jan;33(1):31-46. doi: 10.1007/s00192-021-04907-7. Epub 2021 Aug 18.

**PMID:** 34406418

**Citation:** von Pechmann WS, Mutone M, Fyffe J, Hale DS. Total colpocleisis with high levator plication for the treatment of advanced pelvic organ prolapse. Am J Obstet Gynecol. 2003 Jul;189(1):121-6. doi: 10.1067/mob.2003.546.

**PMID:** 12861149

**Citation:** Hill AJ, Walters MD, Unger CA. Perioperative adverse events associated with colpocleisis for uterovaginal and posthysterectomy vaginal vault prolapse. Am J Obstet Gynecol. 2016 Apr;214(4):501.e1-501.e6. doi: 10.1016/j.ajog.2015.10.921. Epub 2015 Oct 31.

**PMID:** 26529371

**Citation:** Elena Scarafoni E. A Systematic Review of Tranexamic Acid in Plastic Surgery: What's New? Plast Reconstr Surg Glob Open. 2021 Mar 23;9(3):e3172. doi: 10.1097/GOX.0000000000003172. eCollection 2021 Mar.

**PMID:** 33907653

**Citation:** Frishman G. Vasopressin: if some is good, is more better? Obstet Gynecol. 2009 Feb;113(2 Pt 2):476-477. doi: 10.1097/AOG.0b013e31819698bb. No abstract available.

**PMID:** 19155925

**Citation:** Quantitative Blood Loss in Obstetric Hemorrhage: ACOG COMMITTEE OPINION, Number 794. Obstet Gynecol. 2019 Dec;134(6):e150-e156. doi: 10.1097/AOG.0000000000003564.

**PMID:** 31764759

**Citation:** Ker K, Beecher D, Roberts I. Topical application of tranexamic acid for the reduction of bleeding. Cochrane Database Syst Rev. 2013 Jul 23;(7):CD010562. doi: 10.1002/14651858.CD010562.pub2.

**PMID:** 23881695

**Citation:** DILLON TF, MARBURY BE, BONSNES RW, DOUGLAS RG, DU VIGNEAUD V. Vasopressin as a hemostatic in gynecologic surgery; a preliminary report. Obstet Gynecol. 1958 Apr;11(4):363-71. No abstract available.

**PMID:** 13517741

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020763

- Term: Pathological Conditions, Anatomical

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M14261

- Name: Prolapse

- Relevance: HIGH

- As Found: Prolapse

- ID: M28618

- Name: Pelvic Organ Prolapse

- Relevance: HIGH

- As Found: Pelvic Organ Prolapse

- ID: M22519

- Name: Pathological Conditions, Anatomical

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000011391

- Term: Prolapse

- ID: D000056887

- Term: Pelvic Organ Prolapse

### Intervention Browse Module - Ancestors

- ID: D000000933

- Term: Antifibrinolytic Agents

- ID: D000050299

- Term: Fibrin Modulating Agents

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000006490

- Term: Hemostatics

- ID: D000003029

- Term: Coagulants

- ID: D000014662

- Term: Vasoconstrictor Agents

- ID: D000050034

- Term: Antidiuretic Agents

- ID: D000045283

- Term: Natriuretic Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: Coag

- Name: Coagulants

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: PhSol

- Name: Pharmaceutical Solutions

- Abbrev: NaAg

- Name: Natriuretic Agents

- Abbrev: VaCoAg

- Name: Vasoconstrictor Agents

- Abbrev: AA

- Name: Amino Acids

### Intervention Browse Module - Browse Leaves

- ID: M16902

- Name: Tranexamic Acid

- Relevance: HIGH

- As Found: Stage IV

- ID: M4107

- Name: Anesthetics

- Relevance: LOW

- As Found: Unknown

- ID: M21860

- Name: Pharmaceutical Solutions

- Relevance: LOW

- As Found: Unknown

- ID: M17414

- Name: Vasopressins

- Relevance: HIGH

- As Found: Contained

- ID: M4437

- Name: Arginine Vasopressin

- Relevance: HIGH

- As Found: Contained

- ID: M4109

- Name: Anesthetics, Local

- Relevance: LOW

- As Found: Unknown

- ID: M251802

- Name: Imidacloprid

- Relevance: LOW

- As Found: Unknown

- ID: M4252

- Name: Antifibrinolytic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M9576

- Name: Hemostatics

- Relevance: LOW

- As Found: Unknown

- ID: M6259

- Name: Coagulants

- Relevance: LOW

- As Found: Unknown

- ID: M17409

- Name: Vasoconstrictor Agents

- Relevance: LOW

- As Found: Unknown

- ID: T1

- Name: Arginine

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000014667

- Term: Vasopressins

- ID: D000001127

- Term: Arginine Vasopressin

- ID: D000014148

- Term: Tranexamic Acid

### Misc Info Module

- Version Holder: 2024-05-31
