Role of Tranexamic Acid Versus Uterine Cooling at Caesarean Section

Postpartum Hemorrhage Clinical Trial

Official title:

Tranexamic Acid Versus Novel Uterine Cooling Technique in Reducing Blood Loss and Incidence of Postpartum Hemorrhage at Caesarean Section

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02780245
• Other study ID #: OG2
• Status: Completed
• Phase: Phase 4
• First received: May 19, 2016
• Last updated: September 1, 2016
• Start date: June 2016
• Est. completion date: September 2016

Study information

• Verified date: September 2016
• Source: Talkha Central Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Egypt: Ministry of Health and Population
• Study type: Interventional

Clinical Trial Summary

This study aims to compare role of a prophylactic predefined intravenous Tranexamic Acid dose versus intraoperative Uterine Cooling in reducing blood loss and incidence of postpartum hemorrhage at secondary CS.

Description:

Bleeding during vaginal or operative delivery is always of prime concern. Despite significant progress in obstetric care 125,000 women die from obstetric hemorrhage annually in the world.

The incidence of CS is increasing, and the average blood loss during CS (1000 mL) is double the amount lost during vaginal delivery (500 mL). CS rate as high as 25-30% in many areas of the world. In Egypt the CS rate is 27.6 %, in United States of America, from 1970-2009 the CS rate rose from 4.5-32.9%, and declined to 32.8% of all deliveries at 2010. In spite of the various measures to prevent blood loss during and after CS, post-partum hemorrhage (PPH) continues to be the most common complication seen in almost 20% of the cases, and causes approximately 25% of maternal deaths worldwide, leading to increased maternal morbidity and mortality. Women who undergo a CS are much more likely to be delivered by a repeat operation in subsequent pregnancies. For women undergoing subsequent CS, the maternal risks are even greater like massive obstetric hemorrhage, hysterectomy, admission to an intensive care unit, or maternal death. Medications, such as oxytocin, misoprostol and prostaglandin F2α, have been used to control bleeding postoperatively.

TXA is a synthetic analog of the amino acid lysine, as an antifibrinolytic agent. Its intravenous administration has been routinely used for many years to reduce or prevent excessive hemorrhage in various medical conditions or disorders (helping hemostasis), also during and after surgical procedures like benign hysterectomy, open heart surgeries, scoliosis surgery, oral surgery, liver surgeries, total hip or knee arthroplasty, and urology. It has been shown to be very useful and efficient in reducing blood loss and incidence of blood transfusion in these surgeries, and decreases the risk of death in bleeding trauma patients. It was also included in the World Health Organization (WHO) Model List of Essential Medicines.

About its role in CS, some recent studies showed that TXA has advantage and useful effect safely in reducing blood loss and requirement of additional ecbolics. Its doses used intravenously to reduce blood loss at CS were a bolus of 1gm, 10 mg/kg , or 15 mg/kg which had an advantage over 10 mg/kg in anemic parturients.

A recent study by Mitchell et al. concluded that Uterine cooling during cesarean delivery was efficient enough to decrease blood loss and the incidence of postpartum hemorrhage.

This study aims to compare role of a prophylactic predefined intravenous Tranexamic Acid dose versus intraoperative Uterine Cooling in reducing blood loss and incidence of postpartum hemorrhage at secondary CS.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: September 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

Inclusion Criteria:

• Women who attended Talkha Central Hospital for planned or emergency secondary CS.

• Singleton pregnancy at term with gestational age (G.A) between 38±5 and 40 weeks.

Exclusion Criteria:

• Preoperative exclusion criteria were women who had any disorders of heart, liver, kidney, brain or blood, Abruptio placenta, placental abnormalities or accrete syndromes, Polyhydramnios, macrosomia, preeclampsia, allergy to TXA, history of thromboembolic disorders, or severe anemia.

• Intraoperative exclusion criteria was inability to exteriorize the uterus during CS for group (Y).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hemorrhage
• Hemorrhage of Cesarean Section and/or Perineal Wound
• Postpartum Hemorrhage
• Uterine Atony
• Uterine Inertia

Intervention

Drug:
• Tranexamic Acid
At 20 minutes preoperatively, TXA of 20 mg/kg was administered in Z Solution (500•0 ml normal saline containing a prophylactic antibiotic 1•0 g).

Procedure:
• Intraoperative Uterine Cooling
Intraoperatively immediately following delivery of the fetus the uterus was been externalized in the usual fashion, and the body of the uterus cephalad to the hysterotomy incision was been wrapped in sterile surgical towels saturated in sterile and iced normal saline. These towels came from a sterile cooling pot set to 30 degrees Fahrenheit. Iced saline-soaked towels was been kept in place for a minimum of 5 minutes and replaced at the discretion of the attending obstetrician until the hysterotomy is closed and the uterus is replaced into the patient's abdomen.

Locations

Country	Name	City	State
Egypt	Talkha Central Hospital	Mansoura	Al-Dakahliya

Sponsors (1)

Lead Sponsor	Collaborator
Talkha Central Hospital

Country where clinical trial is conducted

Egypt, 

References & Publications (26)

Ahmed MR, Sayed Ahmed WA, Madny EH, Arafa AM, Said MM. Efficacy of tranexamic acid in decreasing blood loss in elective caesarean delivery. J Matern Fetal Neonatal Med. 2015 Jun;28(9):1014-8. doi: 10.3109/14767058.2014.941283. Epub 2014 Jul 28. — View Citation

Cahill AG, Stamilio DM, Odibo AO, Peipert JF, Ratcliffe SJ, Stevens EJ, Sammel MD, Macones GA. Is vaginal birth after cesarean (VBAC) or elective repeat cesarean safer in women with a prior vaginal delivery? Am J Obstet Gynecol. 2006 Oct;195(4):1143-7. Epub 2006 Jul 17. — View Citation

CRASH-2 trial collaborators, Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejía-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto R, Ramana PV, Ravi RR, Yutthakasemsunt S. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010 Jul 3;376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5. Epub 2010 Jun 14. — View Citation

Gai MY, Wu LF, Su QF, Tatsumoto K. Clinical observation of blood loss reduced by tranexamic acid during and after caesarian section: a multi-center, randomized trial. Eur J Obstet Gynecol Reprod Biol. 2004 Feb 10;112(2):154-7. — View Citation

Gaines-Dillard N, Bartley MK, Rosini JM. Tranexamic acid in the trauma patient. Nursing. 2016 Feb;46(2):60-2. doi: 10.1097/01.NURSE.0000476234.78599.e2. — View Citation

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Goswami U, Sarangi S, Gupta S, Babbar S. Comparative evaluation of two doses of tranexamic acid used prophylactically in anemic parturients for lower segment cesarean section: A double-blind randomized case control prospective trial. Saudi J Anaesth. 2013 Oct;7(4):427-31. doi: 10.4103/1658-354X.121077. — View Citation

Gungorduk K, Yildirim G, Asicioglu O, Gungorduk OC, Sudolmus S, Ark C. Efficacy of intravenous tranexamic acid in reducing blood loss after elective cesarean section: a prospective, randomized, double-blind, placebo-controlled study. Am J Perinatol. 2011 Mar;28(3):233-40. doi: 10.1055/s-0030-1268238. Epub 2010 Oct 26. — View Citation

Gupta A, Dwivedi Y, Shakya V, Srivastva U, Saxena A, Agarwal AM, et al. Efficacy of Tranexamic Acid in Reducing Perioperative Blood Loss During Caesarean Section: A Placebo Controlled Double Blind Study. International Journal of Scientific Research 2016, 5(3).

Maged AM, Helal OM, Elsherbini MM, Eid MM, Elkomy RO, Dahab S, Elsissy MH. A randomized placebo-controlled trial of preoperative tranexamic acid among women undergoing elective cesarean delivery. Int J Gynaecol Obstet. 2015 Dec;131(3):265-8. doi: 10.1016/j.ijgo.2015.05.027. Epub 2015 Aug 15. — View Citation

Marshall NE, Fu R, Guise JM. Impact of multiple cesarean deliveries on maternal morbidity: a systematic review. Am J Obstet Gynecol. 2011 Sep;205(3):262.e1-8. doi: 10.1016/j.ajog.2011.06.035. Epub 2011 Jun 15. Review. — View Citation

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Mayur G, Purvi P, Ashoo G, Pankaj D. Efficacy of tranexamic acid in decreasing blood loss during and after cesarean section: a randomized case controlled prospective study. J Obstet Gynecol India 2007, 57(3): 4.

Mitchell JL, Stecher J, Crowson J, Rich D. Uterine Cooling During Cesarean Delivery to Reduce Blood Loss and Incidence of Postpartum Hemorrhage: A Randomized Controlled Trial [31]. Obstetrics & Gynecology. 2015 May 1;125:9S-10S.

Movafegh A, Eslamian L, Dorabadi A. Effect of intravenous tranexamic acid administration on blood loss during and after cesarean delivery. Int J Gynaecol Obstet. 2011 Dec;115(3):224-6. doi: 10.1016/j.ijgo.2011.07.015. Epub 2011 Aug 27. — View Citation

Sekhavat L, Tabatabaii A, Dalili M, Farajkhoda T, Tafti AD. Efficacy of tranexamic acid in reducing blood loss after cesarean section. J Matern Fetal Neonatal Med. 2009 Jan;22(1):72-5. doi: 10.1080/14767050802353580. — View Citation

Sentilhes L, Lasocki S, Ducloy-Bouthors AS, Deruelle P, Dreyfus M, Perrotin F, Goffinet F, Deneux-Tharaux C. Tranexamic acid for the prevention and treatment of postpartum haemorrhage. Br J Anaesth. 2015 Apr;114(4):576-87. doi: 10.1093/bja/aeu448. Epub 2015 Jan 8. Review. — View Citation

Shahid A, Khan A. Tranexamic acid in decreasing blood loss during and after caesarean section. J Coll Physicians Surg Pak. 2013 Jul;23(7):459-62. doi: 07.2013/JCPSP.459462. — View Citation

Silver RM, Landon MB, Rouse DJ, Leveno KJ, Spong CY, Thom EA, Moawad AH, Caritis SN, Harper M, Wapner RJ, Sorokin Y, Miodovnik M, Carpenter M, Peaceman AM, O'Sullivan MJ, Sibai B, Langer O, Thorp JM, Ramin SM, Mercer BM; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Maternal morbidity associated with multiple repeat cesarean deliveries. Obstet Gynecol. 2006 Jun;107(6):1226-32. — View Citation

Simonazzi G, Bisulli M, Saccone G, Moro E, Marshall A, Berghella V. Tranexamic acid for preventing postpartum blood loss after cesarean delivery: a systematic review and meta-analysis of randomized controlled trials. Acta Obstet Gynecol Scand. 2016 Jan;95(1):28-37. doi: 10.1111/aogs.12798. Epub 2015 Nov 12. Review. — View Citation

Sujata N, Tobin R, Kaur R, Aneja A, Khanna M, Hanjoora VM. Randomized controlled trial of tranexamic acid among parturients at increased risk for postpartum hemorrhage undergoing cesarean delivery. Int J Gynaecol Obstet. 2016 Jun;133(3):312-5. doi: 10.1016/j.ijgo.2015.09.032. Epub 2016 Feb 16. — View Citation

Tarabrin O, Kaminskiy V, Galich S, Tkachenko R, Gulyaev A, Shcherbakov S, et al. Efficacy of tranexamic acid in decreasing blood loss during cesarean section. Critical Care 2012, 16(1): 1-189.

Topsoee MF, Bergholt T, Ravn P, Schouenborg L, Moeller C, Ottesen B, Settnes A. Anti-hemorrhagic effect of prophylactic tranexamic acid in benign hysterectomy-a double-blinded randomized placebo-controlled trial. Am J Obstet Gynecol. 2016 Jul;215(1):72.e1-8. doi: 10.1016/j.ajog.2016.01.184. Epub 2016 Jan 30. — View Citation

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Blood Pressure	Measuring maternal blood pressure (mmHg) immediately postoperative and after 3 hours postoperative.	Up to 3 hours	Yes
Other	Maternal Side effects of intervention administered	Recording any Maternal side effects of interventions administered	Up to 9 hours	Yes
Other	APGAR Scores	Recording of APGAR Score (/10) for all neonates immediately after delivery	up to 2 hours	Yes
Other	Pulse Rate	Measuring maternal pulse rate (/minute) immediately postoperative and after 3 hours postoperative.	Up to 3 hours	Yes
Primary	Total blood loss volume	Estimation of Total Blood Loss Volume (ml) during CS and in the PACU.	Up to 3 hours	No
Secondary	Hematocrit value (Hct)	Estimating change in Pre- versus Post-operative hematocrit values (%) at 6 hours postoperatively.	6 hours postoperative period	No
Secondary	Overall blood loss volume greater than 1000 cc	Estimation of overall blood loss volume during CS and up to 6 hours postoperatively	Up to 9 hours	No
Secondary	Need for Additional Ecbolics	Need for additional ecbolics to arrest and manage bleeding if there is a uterine atony	Intraoperative	No
Secondary	Need for other surgical measures to stop bleeding	Need for other surgical measures to stop bleeding (B-lynch denoting uterine atony, uterine artery ligation, hysterectomy)	Intraoperative	No
Secondary	Transfusion of Blood or Blood Products	Need for transfusion of blood or blood products during CS and in the PACU	Up to 3 hours	No