Methods Decreasing Bleeding in Open Myomectomy

NCT05806307 | Unknown Phase 4

• 1 other identifier: AN2023-1
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

Uterine leiomyomas (fibroids or myomas) are benign, smooth muscle tumors of the human uterus. Most myomas are asymptomatic (symptomless) and are discovered incidentally during a routine pelvic examination or imaging studies and have a lifetime incidence of approximately 70% in the general population . However, Approximately 20-40% of women with fibroids experience significant symptoms and consult gynecologic care. The most common clinical symptoms include abnormal uterine bleeding, dysmenorrhea, pelvic pain, infertility, and recurrent pregnancy loss The standard treatment of symptomatic leiomyomas is Abdominal myomectomy Blood loss during myomectomy can be intra-operative or postoperative and with hematoma formation. The average volume of blood loss during abdominal myomectomy is 200 to 800 ml. massive blood loss associated with the dissection of huge fibroids renders myomectomy a more technically challenging procedure than hysterectomy. Sometimes myomectomy is converted to hysterectomy intra-operatively when bleeding becomes heavy and uncontrollable or when it is impossible to reconstruct the uterus because of the many defects left by removal of multiple myomas . Many techniques are used to reduce blood loss during myomectomy; preoperative measures such as correction of preoperative anemia associated with menorrhagia may be treated with iron supplementation, use of gonadotropin (GHG) triggers prior to surgery. Intra-operative measures as use of tourniquet around the uterus during the operation, injections of Vasopressin or other vasopressors as epinephrine in the uterine muscle and use of ecbolic (misoprostol, oxytocin, and carbetocin etc.). Uterine artery ligation, embolization, or internal iliac artery ligation may also be used to avoid hysterectomy when heavy bleeding is anticipated or occurs during myomectomy

Conditions

Misoprostol Allergy; Oxytocin Allergy; Tranexamic Acid Allergy; Ethamsylate Allergy; Myoma; Blood Loss, Surgical

Keywords

misoprostol; oxytocin; carbetocin; tranexamic acid; ethamsylate; tourniquet; blood loss; myomectomy; vasopressin; bupivacaine; epinephrine

Outcome Measures

Primary Outcomes (1)

• blood loss

  the estimated intra-operative blood loss in ml

  3 hours

Secondary Outcomes (5)

• blood transfusion

  24 hours

• Preoperative and postoperative hemoglobin values

  48 hours

• Perioperative blood pressure

  4-6 hours

• the duration of hospital stays

  3 day

• Operation time

  3 hours

Study Arms (7)

misoprostol

ACTIVE COMPARATOR

15 patients will receive 800 microgram (tablet 200mcg X 4) misoprostol (Misotac 200 mcg, SIGMA pharmaceutical, Egypt) rectally one and half hour before operation.

Drug: Misoprostol

Tourniquet

ACTIVE COMPARATOR

(15 patient): The operation will be performed with the use of Foleys catheter as an improvised tourniquet applied at the base of the uterus then infiltration myometrium overlying the leiomyoma with a solution composed of Bupivacaine Hcl 0.25% and 0.5 mg of epinephrine

Device: Tourniquet

Carbetocin

ACTIVE COMPARATOR

intramural; preparation of 100 μg of carbetocin ((Pabal, Ampoule 100 mcg in 1 ml, Carbetocin; FERRING, North York, Canada) diluted within 10 cm of saline (0.9%) in sterile syringe then will inject the substance into the multiple sites intramyometrial in a circumferential manner 1-2 cm away from the margins of the myoma in the planned uterine-incision site just before uterine incision for myoma extraction.

Drug: Carbetocin

Oxytocin

ACTIVE COMPARATOR

15 patients): who will receive oxytocin 40 I.U. intramyometrially (Syntocinon, Ampule 10 I.U. in 1 ml, Oxytocin; NOVARTIS, Basel, Switzerland) then will inject the substance into the multiple sites intramyometrial in a circumferential manner 1-2 cm away from the margins of the myoma in the planned uterine-incision site just before uterine incision for myoma extraction.

Drug: Oxytocin

combined TXA and ethamsylate

ACTIVE COMPARATOR

(Patient 15): will receive 1 g tranexamic acid (2 ampoules of kapron 500 mg, kapron®, Amoun, Egypt) and 500 mg ethamsylate (2 ampoule of ethamsylate 250 mg, Dicynone, OM pharma, Geneva, Switzerland) IV 10 minutes before skin incision by slowly intravenous injection Then infusion was applied continuously for 24 hours within 1 liter of saline as 1 mg/kg/hour.

Drug: combined TXA and ethamsylate

vasopressin

ACTIVE COMPARATOR

15 women will receive terlipressin (Glypressin, Ferring, Egypt) intramyometrial injection of one ampoule of vasopressin containing 20 units in1 ml after dilution in 19 ml of normal saline during myomectomy.

Drug: Vasopressin

bupivacaine and epinephrine

ACTIVE COMPARATOR

15 women in which the operation will be performed after infiltration of the serosa and / or myometrium overlying the leiomyoma before uterine incision with a solution composed of 50 ml Bupivacaine Hcl 0.25% (Bucain® Weimer pharma, for Actavis Group PTC) and 0.5 mg of epinephrine Hcl (2 vials of Epinephrine® 0.25mg/1ml Misr Co. for Pharmaceutical Industries).

Drug: Bupivacaine Hydrochloride 0.5 % Injectable Solution epinephrine

Interventions

Misoprostol DRUG

(15 patient): who will receive 800 microgram (tablet 200mcg X 4) misoprostol (Misotac 200 mcg, SIGMA pharmaceutical, Egypt) rectally one and half hour before operation.

Also known as: Misotac

misoprostol

Tourniquet DEVICE

(15 patient): The operation will be performed with the use of Foleys catheter as an improvised tourniquet applied at the base of the uterus then infiltration myometrium overlying the leiomyoma with a solution composed of Bupivacaine Hcl 0.25% and 0.5 mg of epinephrine

Also known as: Foleys catheter

Tourniquet

Carbetocin DRUG

(15 patients): intramural; preparation of 100 μg of carbetocin ((Pabal, Ampoule 100 mcg in 1 ml, Carbetocin; FERRING, North York, Canada) diluted within 10 cm of saline (0.9%) in sterile syringe then will inject the substance into the multiple sites intramyometrial in a circumferential manner 1-2 cm away from the margins of the myoma in the planned uterine-incision site just before uterine incision for myoma extraction.

Also known as: pabal

Carbetocin

Oxytocin DRUG

(15 patients): who will receive oxytocin 40 I.U. intramyometrially (Syntocinon, Ampule 10 I.U. in 1 ml, Oxytocin; NOVARTIS, Basel, Switzerland) then will inject the substance into the multiple sites intramyometrial in a circumferential manner 1-2 cm away from the margins of the myoma in the planned uterine-incision site just before uterine incision for myoma extraction.

Also known as: syntocinone

Oxytocin

combined TXA and ethamsylate DRUG

(Patient 15): will receive 1 g tranexamic acid (2 ampoules of kapron 500 mg, kapron®, Amoun, Egypt) and 500 mg ethamsylate (2 ampoule of ethamsylate 250 mg, Dicynone, OM pharma, Geneva, Switzerland) IV 10 minutes before skin incision by slowly intravenous injection Then infusion was applied continuously for 24 hours within 1 liter of saline as 1 mg/kg/hour.

Also known as: Kapron and Dycinone

combined TXA and ethamsylate

Vasopressin DRUG

15 patient intramyometrial injection of one ampoule of vasopressin containing 20 units in1 ml after dilution in 19 ml of normal saline during myomectomy.

Also known as: Glypressin

vasopressin

Bupivacaine Hydrochloride 0.5 % Injectable Solution epinephrine DRUG

15 patient infiltration of the serosa and / or myometrium overlying the leiomyoma before uterine incision with a solution composed of 50 ml Bupivacaine Hcl 0.25% (Bucain® Weimer pharma, for Actavis Group PTC) and 0.5 mg of epinephrine Hcl (2 vials of Epinephrine® 0.25mg/1ml Misr Co. for Pharmaceutical Industries).

Also known as: marcaine

bupivacaine and epinephrine

Eligibility Criteria

• Age: 25 Years - 48 Years
• Gender Eligibility Details: Patients will be recruited in this study from those attending gynecology ward at Kasr al-ainy hospitals, Maternity hospital who are 25-48 years old with symptomatic uterine myoma indicating operative management, abnormal uterine bleeding or bulk-related symptoms, females with infertility or recurrent pregnancy loss, pressure symptoms, and large myoma(s).
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• patients aged between 25 to 48 years old.
• BMI less than 35 kg/m2
• symptomatic uterine myomas..
• myoma staging from (3 to 6) according to FIGO staging through trans vaginal ultrasonography (TVUSG) or magnetic resonance imaging (MRI) according to FIGO classification.
• Maximum diameter of the largest myoma is 15 cm.
• Uterine size between 14 to 28 weeks pregnancy.

You may not qualify if:

• History of previous myomectomy
• Allergy to Misoprostol, carbetocin, TXA, ethamsylate, Oxytocin, vasopressin, bupivacaine and epinephrine.
• Hypertension.
• Cardiac and Pulmonary diseases.
• Patients who have bleeding disorders.
• Patients on antiplatelets or anticoagulant before surgery.
• Anemia (Hb \< 10g %).
• Chronic endocrine or metabolic diseases such as Diabetes.
• Renal and hepatic impairment.
• Obesity (body mass index \> 30 kg/m2).
• Cases that will require intraoperative conversion of myomectomy to hysterectomy.
• Intracavitary, submucosal, pedunculated Subserosal and adnexal Myoma FIGO staging 0,1,2,7,8.
• history of Gynecological infections (PID), history of abdominal infections e.g.: peritonitis, history of any abdominal or pelvic operation for non-obstetric cause.

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

faculty of medicine, Kasr el ainy hospital, Cairo university

Cairo, 11562, Egypt

RECRUITING

Related Publications (10)

• Cooper JM, Brady RM. Intraoperative and early postoperative complications of operative hysteroscopy. Obstet Gynecol Clin North Am. 2000 Jun;27(2):347-66. doi: 10.1016/s0889-8545(00)80026-1.

  PMID: 10857125 BACKGROUND

• Donnez J, Dolmans MM. Uterine fibroid management: from the present to the future. Hum Reprod Update. 2016 Nov;22(6):665-686. doi: 10.1093/humupd/dmw023. Epub 2016 Jul 27.

  PMID: 27466209 BACKGROUND

• 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.

  PMID: 25125317 BACKGROUND

• Krentel H, De Wilde RL. Complications in Laparoscopic Supracervical Hysterectomy(LASH), especially the morcellation related. Best Pract Res Clin Obstet Gynaecol. 2016 Aug;35:44-50. doi: 10.1016/j.bpobgyn.2015.11.001. Epub 2015 Nov 14.

  PMID: 26694587 BACKGROUND

• Mohamed, S. E. S., Mansour, D. Y., & Shaker, A. N. (2019). The effect of misoprostol on intra-operative blood loss during myomectomy operation: Randomized controlled trial. Evidence Based Women's Health Journal, 9(1), 363-371.

  BACKGROUND

• Shady, N. W., Sallam, H. F., & Fahmy, H. (2018). Reducing blood loss during open myomectomy with intravenous versus topical tranexamic acid: A double-blinded randomized placebo-controlled trial. Middle East Fertility Society Journal, 23(3), 225-231.

  BACKGROUND

• Sirkeci RF, Belli AM, Manyonda IT. Treating symptomatic uterine fibroids with myomectomy: current practice and views of UK consultants. Gynecol Surg. 2017;14(1):11. doi: 10.1186/s10397-017-1014-4. Epub 2017 Jul 6.

  PMID: 28890674 BACKGROUND

• Sleiman Z, Baba RE, Garzon S, Khazaka A. The Significant Risk Factors of Intra-Operative Hemorrhage during Laparoscopic Myomectomy: A Systematic Review. Gynecol Minim Invasive Ther. 2019 Nov 11;9(1):6-12. doi: 10.4103/GMIT.GMIT_21_19. eCollection 2020 Jan-Mar.

  PMID: 32090006 BACKGROUND

• M Al-Morsi, A., N Abdul-Galeel, K., & A El-Desouky, E. S. (2021). Comparative study between oxytocin versus tranexamic acid and ethamsylate combination in reducing intraoperative blood loss in myomectomy. Al-Azhar Medical Journal, 50(3), 1893-1908.

  BACKGROUND

• Camanni M, Bonino L, Delpiano EM, Ferrero B, Migliaretti G, Deltetto F. Hysteroscopic management of large symptomatic submucous uterine myomas. J Minim Invasive Gynecol. 2010 Jan-Feb;17(1):59-65. doi: 10.1016/j.jmig.2009.10.013.

  PMID: 20129334 RESULT

MeSH Terms

Conditions

Myoma; Blood Loss, Surgical; Hemorrhage; Diabetes Insipidus

Interventions

Misoprostol; Tourniquets; carbetocin; Oxytocin; Ethamsylate; Vasopressins; Terlipressin; Bupivacaine

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intraoperative Complications; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Prostaglandins E, Synthetic; Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors; Equipment and Supplies; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Neuropeptides; Oligopeptides; Nerve Tissue Proteins; Proteins; Lypressin; Anilides; Amides; Aniline Compounds; Amines

Study Officials

• Mohammed A Taymour, MD

  Cairo University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

waleed M El-khayat, MD

CONTACT

01005135542; waleed_elkhyat@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: lecturer

Model Details: Intervention All women will be randomly assigned to either: Group A (misoprostol): who will receive 800 microgram misoprostol rectally one and half hour before operation. Group B (Tourniquet): The operation will be performed with the use of Foleys catheter as an improvised tourniquet applied at the base of the uterus. Group C (Carbetocin): intramural; preparation of 100 μg of carbetocin diluted within 10 cm of saline (0.9%) Group D (Oxytocin): who will receive oxytocin 40 I.U. intramyometrially Group E (combined TXA and ethamsylate): will receive 1 g tranexamic acid and 500 mg ethamsylate IV 10 minutes before skin incision Group F receive terlipressin intramyometrial injection of one ampoule of vasopressin containing 20 units in1 ml after dilution in 19 ml of normal saline. Group G: infiltration of the serosa and / or myometrium with a solution composed of 50 ml Bupivacaine 0.25% and 0.5 mg of epinephrine

Study Record Dates

• First Submitted: March 10, 2023
• First Posted: April 10, 2023
• Study Start: March 15, 2023
• Primary Completion: October 30, 2023
• Study Completion: November 30, 2023
• Last Updated: April 10, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)