Tranexamic Acid in Vaginal Reconstructive Surgery

Pelvic Organ Prolapse Clinical Trial

— TEXAS  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06419075
• Other study ID #: 23-0273
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: July 1, 2024
• Est. completion date: March 1, 2026

Study information

• Verified date: May 2024
• Source: The University of Texas Medical Branch, Galveston
• Contact: Trieu H Do, MD
• Phone: 8326327964
• Email: trhdo[@]utmb.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 36
• Est. completion date: March 1, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 50 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Pelvic Organ Prolapse
• Prolapse

Intervention

Drug:
• Tranexamic acid
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.
• Vasopressin
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.

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

Locations

Country	Name	City	State
United States	University of Texas Medical Branch Galveston	Galveston	Texas

Sponsors (3)

Lead Sponsor	Collaborator
The University of Texas Medical Branch, Galveston	MOUNT SINAI HOSPITAL, The University of Texas Health Science Center, Houston

Country where clinical trial is conducted

United States, 

References & Publications (26)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intraoperative quantitative blood loss QBL (mL)	Compare intraoperative QBL during colpocleisis with the local infiltration of Tranexamic acid to the current standard of care, vasopressin or normal saline.	Intraoperatively
Secondary	Colpocleisis operative time (min)	Compare the colpocleisis operative time between Tranexamic acid, vasopressin or normal saline groups	Intraoperatively
Secondary	Intraoperative blood pressure (mmHg)	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.	Intraoperatively
Secondary	Intraoperative hear rate (beats/min)	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.	Intraoperatively
Secondary	Postoperative complications	Assess postoperative complications following colpocleisis using the Clavien-Dindo Classification (CDC) categories	2 weeks and 6 weeks postoperatively
Secondary	Rate of transfusion	Quantify the need for blood-product transfusion and the volume administered as a direct result of colpocleisis, either intraoperative or postoperative	Intraoperatively and 2 weeks postoperatively