Tranexamic Acid in Vaginal Reconstructive Surgery

NCT06419075 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: 23-0273
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Pelvic Organ Prolapse

Keywords

Tranexamic Acid; Colpocleisis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Colpocleisis operative time (min)

  Intraoperatively

• Intraoperative blood pressure (mmHg)

  Intraoperatively

• Intraoperative hear rate (beats/min)

  Intraoperatively

• Postoperative complications

  2 weeks and 6 weeks postoperatively

• Rate of transfusion

  Intraoperatively and 2 weeks postoperatively

Study Arms (3)

Normal Saline (NaCl 0.9%)

PLACEBO COMPARATOR

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

Other: NaCl 0.9%

Tranexamic Acid (2 mg/dL)

EXPERIMENTAL

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

Drug: Tranexamic acid

Vasopressin (0.1 U/dL)

EXPERIMENTAL

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

Drug: Vasopressin

Interventions

Tranexamic acid DRUG

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.

Also known as: Tranexamic acid (CYKLOKAPRON) (Pfizer, New York, NY).

Tranexamic Acid (2 mg/dL)

Vasopressin DRUG

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.

Also known as: Vasopressin (Vasostrict) (Par Pharmaceutical, Chestnut Ridge, NY).

Vasopressin (0.1 U/dL)

NaCl 0.9% OTHER

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

Normal Saline (NaCl 0.9%)

Eligibility Criteria

• Age: 50 Years - 100 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• The University of Texas Medical Branch, Galveston: lead
• MOUNT SINAI HOSPITAL: collaborator
• The University of Texas Health Science Center, Houston: collaborator

Related Publications (26)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

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• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

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• 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.

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• 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 BACKGROUND

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MeSH Terms

Conditions

Pelvic Organ Prolapse

Interventions

Tranexamic Acid; Vasopressins; Arginine Vasopressin; Sodium Chloride

Condition Hierarchy (Ancestors)

Prolapse; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Gokhan Kilic, MD

  University of Texas Medical Branch Galveston

  PRINCIPAL INVESTIGATOR

• Ann Tran, MD

  Mount Sinai Hospital & Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 8, 2024
• First Posted: May 17, 2024
• Study Start: July 1, 2024
• Primary Completion: January 27, 2025
• Study Completion: January 27, 2025
• Last Updated: January 31, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share