Clinical trial NCT04482959: Intraoperative Carbetocin to Decrease Blood Loss During Hysteroscopic Myomectomy
Official title: Intraoperative Carbetocin to Decrease Blood Loss During Hysteroscopic Myomectomy: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myoma;Uterus
Lead sponsor: Mansoura University Hospital
Sponsor class: OTHER
First posted: 2020-07-23
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial (RCT).
Primary purpose: PREVENTION

Brief summary: Submucous myomas represent one of the main indications of operative hysteroscopy. Since 1976 when Neuwirth and Amin reported the first five cases of excision of submucous myomas , several techniques have been developed in order to render hysteroscopic myomectomy a safe and effective procedure .

Hysteroscopic myomectomy is currently considered the "gold standard" minimally invasive approach for the treatment of symptomatic submucous myomas . Patients undergoing hysteroscopic myomectomy are liable to significant blood loss, and hemodynamic and hematological disturbances. Excessive bleeding during hysteroscopic myomectomy remains a major challenge for the endoscopic gynecological surgeons. Many interventions were introduced to reduce the risk of bleeding during myomectomy. These include the use of utero-tonics such as oxytocin, or the use of anti-fibrinolytics such as tranexamic acid . The potential advantage of oxytocin infusion during hysteroscopic myomectomy is that it can maintains uterine contractility throughout the procedure, and thus, reduce blood loss .

Carbetocin (1-deamino-1-monocarba-(0-2-methyltyrosine)-oxytocin) is a long-acting synthetic agonist analogue of the human oxytocin. When injected to a woman, it induces uterine contractions . Although many interventions have been described to reduce the intraoperative blood loss during hysteroscopic myomectomy, there is a need for a well-designed randomized controlled trials to identify the most efficient interventions, with reasonable safety profiles, to help the perform a safe and curative surgery.

Detailed description: All patients will have preoperative evaluation by gynecologists and anesthetists, with history taking and pelvic examination. A TVS scan will be done to determine the number, size and location of the myomas, and evaluate the myometrial free margin (the minimum thickness between the outer edge of the myoma and inner edge of the uterine serosa), which was found to be ideally ≥ 10 mm (11). Prior office diagnostic hysteroscopy will be performed for evaluation of the number, location and grade of the submucous myomas, and assessment of the endocervical canal and uterine cavity and the position of the tubal ostia in order to aid orientation. Preoperative full blood count, serum creatinine, fasting blood glucose, liver enzymes, coagulation profile ( INR), and viral markers will be done for all the patients. Monopolar resectoscopic myomectomies will be scheduled in the proliferative phase of menstrual cycle by a single experienced operator.

After induction of general anesthesia, immediately before the operation, participants will receive either 1 ml of carbetocin (100 mcg/ml) IV over 1 minute (study group) or 1 ml of sodium chloride 0.9% IV over 1 minute (control group). The procedure will be done using the available standard setup and the distending solution used will be 1.5% glycine. A drape with a fluid-collection pouch (Lingeman 3 in 1 Procedure Drape, Lingeman Medical Products, Inc., Indianapolis, IN) placed beneath the woman's buttocks will be used to collect outflow fluid escaping between the cervix and sheath to prevent spillage of irrigating fluid onto the floor. Fluid inflow and outflow will be monitored every 3-5 minutes. The outflow fluid will be measured to the nearest milliliter. The inflow and outflow volumes of the distension solution will be carefully monitored continuously during the procedure by nurses not involved in the study under the current monitoring protocol at the operating theater. The procedure would be terminated if the fluid imbalance reached 1 L.

After completing the procedure, the surgeon completed a record sheet for rating of bleeding amount and the quality of operative view. Postoperative full blood count will be done for all patients 24 hours after the procedures. Preoperative and postoperative hemoglobin and hematocrit, the need for blood transfusion, the duration of operation, any operative complications and medication adverse effects will be recorded.

Eligibility criteria: Inclusion Criteria:

* Symptomatic women aged 18-45 years diagnosed by transvaginal sonography (TVS) to have single type 0 or I submucous uterine myomas according to FIGO classification system with a largest diameter ≤ 4 cm and myometrial free margin of at least 10 mm.

Exclusion Criteria:

* • Age \< 18 or \> 45 years.

  * Uterine septum or structural uterine abnormality (including multiple uterine fibroids and/or multiple submucous myomas)
  * Present or history of cervical or uterine malignancies.
  * Active pelvic infection.
  * Chronic medical diseases (cardiopulmonary, thromboembolic, hepatic, or renal diseases).
  * Bleeding disorders.
  * Patients receiving anticoagulant therapy.
  * Patients receiving gonadotropin-releasing hormone (GnRH) analogues.
  * History of adverse reaction contraindications for Carbetocin.

Primary outcomes:
measure: intraoperative bleeding amount
timeFrame: Time Frame: Start with the first resectoscope myoma cut till withdrawal of hysteroscope through the cervix at the end of the procedure
measure: • Change in haemoglobin and hematocrit
timeFrame: Haemoglobin and hematocrit values 24 hours before myomectomy and 24 hour after myomectomy
Secondary outcomes:
measure: • Operative time
timeFrame: Start with insertion of hysteroscope through the cervix ends with withdrawal of hysteroscopy through the cervix at the end of the procedure
measure: • Fluid deficit
timeFrame: start with insertion of hysteroscope through the cervix ends with withdrawal of hysteroscopy through the cervix at the end pf the procedure
measure: • The quality of operative view
timeFrame: start with the first resectoscope myoma cut till the completion of myoma resection
Other outcomes:
Locations:
city: Mansoura
country: Egypt
facility: Faculty of Medicine
state: Dakahlia
Study officials:
affiliation: Faculty of Medicine - Mansoura University
name: Mohamed E Taman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Neuwirth RS, Amin HK. Excision of submucus fibroids with hysteroscopic control. Am J Obstet Gynecol. 1976 Sep 1;126(1):95-9. doi: 10.1016/0002-9378(76)90471-3.
citation: Di Spiezio Sardo A, Mazzon I, Bramante S, Bettocchi S, Bifulco G, Guida M, Nappi C. Hysteroscopic myomectomy: a comprehensive review of surgical techniques. Hum Reprod Update. 2008 Mar-Apr;14(2):101-19. doi: 10.1093/humupd/dmm041. Epub 2007 Dec 6.
citation: Deutsch A, Sasaki KJ, Cholkeri-Singh A. Resectoscopic Surgery for Polyps and Myomas: A Review of the Literature. J Minim Invasive Gynecol. 2017 Nov-Dec;24(7):1104-1110. doi: 10.1016/j.jmig.2017.08.645. Epub 2017 Aug 24.
citation: Malm M, Madsen I, Kjellstrom J. Development and stability of a heat-stable formulation of carbetocin for the prevention of postpartum haemorrhage for use in low and middle-income countries. J Pept Sci. 2018 Jun;24(6):e3082. doi: 10.1002/psc.3082. Epub 2018 Apr 27.
citation: Munro MG, Critchley HO, Broder MS, Fraser IS; FIGO Working Group on Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011 Apr;113(1):3-13. doi: 10.1016/j.ijgo.2010.11.011. Epub 2011 Feb 22.