Pelvic Organ Prolapse
Conditions
Keywords
Tranexamic Acid, Colpocleisis
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
Interventions
DRUGTranexamic 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.
DRUGVasopressin
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.
OTHERNaCl 0.9%
The intervention of 50 cc NaCl 0.9% local infiltration serves a placebo control.
Sponsors
MOUNT SINAI HOSPITAL
The University of Texas Health Science Center, Houston
The University of Texas Medical Branch, Galveston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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.
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.
Eligibility
Sex/Gender
FEMALE
Age
50 Years to 100 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intraoperative quantitative blood loss QBL (mL) | Intraoperatively | Compare intraoperative QBL during colpocleisis with the local infiltration of Tranexamic acid to the current standard of care, vasopressin or normal saline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Colpocleisis operative time (min) | Intraoperatively | Compare the colpocleisis operative time between Tranexamic acid, vasopressin or normal saline groups |
| Intraoperative blood pressure (mmHg) | Intraoperatively | 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. |
| Intraoperative hear rate (beats/min) | Intraoperatively | 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. |
| Postoperative complications | 2 weeks and 6 weeks postoperatively | Assess postoperative complications following colpocleisis using the Clavien-Dindo Classification (CDC) categories |
| Rate of transfusion | Intraoperatively and 2 weeks postoperatively | Quantify the need for blood-product transfusion and the volume administered as a direct result of colpocleisis, either intraoperative or postoperative |
Outcome results
None listed