Clinical trial NCT04311073: Prophylactic Tranexamic Acid During Minimally Invasive Myomectomies
Official title: Randomized Control Trial Investigating for Prophylactic Tranexamic Acid Use at Time of Minimally Invasive Myomectomies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Fibroid Uterus
Abnormal Uterine Bleeding
Myoma;Uterus
Keywords: Tranexamic acid
Minimally Invasive
Myomectomy
Fibroid
Lead sponsor: Eastern Virginia Medical School
Sponsor class: OTHER
First posted: 2020-03-17
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Double Blind Placebo clinical trial
Primary purpose: PREVENTION

Brief summary: This is a Double-blinded randomized placebo-controlled trial based at Eastern Virginia Medical School. Subjects who are identified in clinic having menorrhagia or abnormal Uterine bleeding (AUB) due to uterine fibroids and meet inclusion criteria based on the ultrasound (US) or Magnetic Resonance Imaging (MRI), aged 18-45 undergoing laparoscopic or Robotic assisted myomectomies. A total of 50 women in each arm of the study with symptomatic fibroids. Patients will be randomized to receive a single IV bolus injection of TXA 30mg/kg in 50ml of normal saline (intervention group) versus an IV bolus injection of normal saline of equivalent volume (placebo group) 15 minutes prior to initial surgical incision.

Detailed description: This is a Double-blinded randomized placebo-controlled trial based at Eastern Virginia Medical School. Subjects who are identified in clinic having menorrhagia or abnormal Uterine bleeding (AUB) due to uterine fibroids and meet inclusion criteria based on the ultrasound (US) or Magnetic Resonance Imaging (MRI), aged 18-45 undergoing laparoscopic or Robotic assisted myomectomies. These subjects will be then approached for consent during their pre-op visit 1-2 weeks prior to their surgery. The setting for consent will be in a patient consultation room. A total of 50 women in each arm of the study with symptomatic fibroids meeting any of the following criteria will be included in the study:

1. At least one fibroid greater than or equal to 6 cm
2. Any intramural or broad ligament fibroid greater than or equal to 4 cm
3. At least 3 total fibroids based on preoperative imaging. Randomization will be performed using an automated randomization website Patients will be randomized to receive a single IV bolus injection of TXA 30mg/kg in 50ml of normal saline (intervention group) versus an IV bolus injection of normal saline of equivalent volume (placebo group) 15 minutes prior to initial surgical incision. This dosage will not be adjusted for patients with renal insufficiency as they will be excluded from the study. Preparation of the medications will be performed by anesthesia who have both medication and normal saline available to them on short notice. No prior preparation by pharmacy will be required. Tranexamic acid is readily available in a 10 ml vial, which does not need a pharmacist to prepare for administration. The vial is mixed with 50 ml of saline in the operating room. This is the same process that occurs outside of any study with any medication that is administered intra-operatively. This will in no way impact the patient's safety during the surgery, especially since it is administered 15 minutes prior to the start of the procedure.

Both surgeon and patient will be blinded to the treatment arm. This dosage has been used previously in both obstetric and gynecological procedures and is the same dose recommended by the WHO for preventing post-partum hemorrhage The surgery itself will be scheduled at either Sentara Norfolk General, Sentara Leigh hospital, and Sentara Princess Anne hospital. These are the three sites that the investigators already perform Minimally invasive myomectomies.

An envelope will be given to the anesthesiologist prior to the procedure informing whether they are to receives TXA or the placebo. Blood loss will be estimated by the surgeon performing the procedure. Hemoglobin and hematocrit will be obtained 24 hours post procedure. The patient will be assessed for reported side effects from the medication given will be assessed by a questionnaire that will be given at their post-op appointment at the 2 week and 6-week mark. During these two visits a physical exam is performed, checking incision sites, and patient symptoms, all of which are standard of care for any minimally invasive procedure. The patients will be seen at the EVMS outpatient clinic for Gynecology, or depending with the physician who performed the surgery. Data will be collected from both Allscripts and EPIC charts.

Eligibility criteria: Inclusion Criteria:

* Undergoing laparoscopic myomectomy
* At least one fibroid greater than or equal to 6 cm
* Any intramural or broad ligament fibroid greater than or equal to 4 cm
* At least 3 total fibroids based on preoperative imaging

Exclusion Criteria:

* Severe existing medical complications involving the heart, liver, or kidney
* Moderate to severe renal impairment (serum creatinine \> 1.4)
* Blood clotting abnormalities
* Known Allergies to tranexamic acid
* Known Contraindications to Minimally invasive myomectomies
* If you are pregnant
* History of a prior blood clot in the lung arm or leg, known as pulmonary embolism or deep vein thrombosis
* Any active blood clots, clotting disease, pulmonary embolism, cerebral thrombosis, estrogen use, renal impairment, elevated creatinine level
* History of a stroke or mini-strokes
* Concurrent oral contraceptive use
* Contraindications to receiving Tranexamic acid
* In patients with acquired defective color vision, since this prohibits measuring one endpoint that should be followed as a measure of toxicity
* In patients with subarachnoid hemorrhage. Anecdotal experience indicates that cerebral edema and cerebral infarction may be caused by tranexamic acid in such patients.
* In patients with active intravascular clotting.
* In patients with hypersensitivity to tranexamic acid or any of the ingredients

Primary outcomes:
measure: Estimated blood loss
timeFrame: Duration of procedure up to 420 minutes
measure: Calculated blood loss
timeFrame: From post operative day 0 until postoperative day 1
measure: Number of blood products received
timeFrame: Duration of hospital stay up to two days
Secondary outcomes:
measure: Duration of surgery
timeFrame: Duration of surgery up to 420 minutes
measure: Length of hospital stay
timeFrame: Duration of stay in hospital, up to two days
measure: Number of fibroids removed
timeFrame: Duration of surgery, up to 420 minutes
measure: Fibroid type
timeFrame: through completion of study average 8 weeks
measure: Weight of fibroids removed
timeFrame: duration of surgery up to 420 minutes
measure: Pain index
timeFrame: duration of hospital stay, up to two days
measure: Incidence of postoperative complication
timeFrame: Duration of hospital stay , up to two days
measure: Questionnaire for incidence of mild side effect of medication
timeFrame: only on postoperative day 1 , one day
measure: Questionnaire for incidence of serious side effect of medication
timeFrame: Only on postoperative day 1, one day
measure: tPA receptor
timeFrame: From time of randomization until postoperative visit, four weeks
measure: PAI-1 receptor
timeFrame: From time of randomization until postoeprative visit, four weeks
Other outcomes:
Locations:
city: Norfolk
country: United States
facility: EasternVMC
state: Virginia
Study officials:
affiliation: Eastern Virginia Medical School
name: Seifeldin Sadek, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Topsoee MF, Settnes A, Ottesen B, Bergholt T. A systematic review and meta-analysis of the effect of prophylactic tranexamic acid treatment in major benign uterine surgery. Int J Gynaecol Obstet. 2017 Feb;136(2):120-127. doi: 10.1002/ijgo.12047. Epub 2016 Dec 9.
citation: Moore EE, Moore HB, Gonzalez E, Chapman MP, Hansen KC, Sauaia A, Silliman CC, Banerjee A. Postinjury fibrinolysis shutdown: Rationale for selective tranexamic acid. J Trauma Acute Care Surg. 2015 Jun;78(6 Suppl 1):S65-9. doi: 10.1097/TA.0000000000000634.
citation: Hickman LC, Kotlyar A, Shue S, Falcone T. Hemostatic Techniques for Myomectomy: An Evidence-Based Approach. J Minim Invasive Gynecol. 2016 May-Jun;23(4):497-504. doi: 10.1016/j.jmig.2016.01.026. Epub 2016 Mar 9.
citation: Henry DA, Carless PA, Moxey AJ, O'Connell D, Stokes BJ, Fergusson DA, Ker K. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD001886. doi: 10.1002/14651858.CD001886.pub3.
citation: Kongnyuy EJ, Wiysonge CS. Interventions to reduce haemorrhage during myomectomy for fibroids. Cochrane Database Syst Rev. 2014 Aug 15;2014(8):CD005355. doi: 10.1002/14651858.CD005355.pub5.
citation: Opoku-Anane J, Vargas MV, Moawad G, Cherie M, Robinson JK. Use of Intravenous Tranexamic Acid During Myomectomy: A Randomized Double-Blind Placebo Controlled Trial. J Minim Invasive Gynecol. 2015 Nov-Dec;22(6S):S197. doi: 10.1016/j.jmig.2015.08.715. Epub 2015 Oct 15. No abstract available.
citation: Parker WH. Uterine myomas: management. Fertil Steril. 2007 Aug;88(2):255-71. doi: 10.1016/j.fertnstert.2007.06.044. Epub 2007 Jul 20.
citation: Lam SJ, Best S, Kumar S. The impact of fibroid characteristics on pregnancy outcome. Am J Obstet Gynecol. 2014 Oct;211(4):395.e1-5. doi: 10.1016/j.ajog.2014.03.066. Epub 2014 Apr 3.
citation: WHO Recommendation on Tranexamic Acid for the Treatment of Postpartum Haemorrhage. Geneva: World Health Organization; 2017. Available from http://www.ncbi.nlm.nih.gov/books/NBK493081/
citation: Ngichabe S, Obura T, Stones W. Intravenous tranexamic acid as an adjunct haemostat to ornipressin during open myomectomy. A randomized double blind placebo controlled trial. Ann Surg Innov Res. 2015 Oct 31;9:10. doi: 10.1186/s13022-015-0017-y. eCollection 2015.