Role Of Different Prophylactic Doses Of Intravenous Tranexamic Acid In Reducing Blood Loss At Caesarean Section

Postpartum Hemorrhage Clinical Trial

Official title:

Comparative Study For Role Of Different Prophylactic Doses Of Intravenous Tranexamic Acid In Reducing Blood Loss At Caesarean Section: A Randomised Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02739815
• Other study ID #: OG1
• Status: Completed
• Phase: Phase 4
• First received: April 4, 2016
• Last updated: June 14, 2016
• Start date: April 2016
• Est. completion date: June 2016

Study information

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

Clinical Trial Summary

This study aims to define a safe prophylactic intravenous TXA dose with an advantage over others in reducing total blood loss volume at secondary uncomplicated LSCS.

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,10 as an antifibrinolytic agent it has roughly eight times the antifibrinolytic activity of an older analogue; ε-aminocaproic acid. It competitively inhibits the activation of plasminogen to plasmin, by binding to specific sites of both plasminogen and plasmin, a molecule responsible for the degradation of fibrin, a protein that forms the framework of blood clots. 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. No defined safe prophylactic intravenous TXA dose being found in searching literature having an advantage over other doses in reducing total blood loss especially at secondary uncomplicated LSCS.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

Inclusion Criteria:

• Maternal average age of 20-40 years.

• Singleton pregnancy at term between 38±5 days and 40 weeks.

• Elective planned or emergency secondary lower segment caesarean sections (LSCS).

Exclusion Criteria:

• Women with severe medical and surgical complications as any of the following will be excluded :

• Heart, liver, kidney, or brain diseases, and blood disorders.

• Abruptio placenta, and placental abnormalities or accrete syndromes.

• Polyhydramnios, macrosomia, preeclampsia, or allergy to tranexamic acid.

• History of thromboembolic disorders, or severe anemia.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hemorrhage
• Hemorrhage of Cesarean Section and/or Perineal Wound
• Postpartum Hemorrhage

Intervention

Drug:
• Normal Saline containing a prophylactic Antibiotic 1 g
500 ml of normal saline containing a prophylactic Antibiotic 1 g.
• Tranexamic Acid
Tranexamic acid

Locations

Country	Name	City	State
Egypt	Al-Azhar University, Faculty of Medicine for Boys ( Cairo ), Al-Hussein University Hospital	Cairo

Sponsors (2)

Lead Sponsor	Collaborator
Talkha Central Hospital	Al-Azhar University

Country where clinical trial is conducted

Egypt, 

References & Publications (25)

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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

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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

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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

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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

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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

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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 Jan 30. pii: S0002-9378(16)00234-9. doi: 10.1016/j.ajog.2016.01.184. [Epub ahead of print] — View Citation

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* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Blood Loss Volume	Estimating Total Blood Loss Volume (ml) during and after Caesarean Section, up to 6 hours post-operative.	Up to 7 hours	Yes
Secondary	Duration of surgery	Duration of Caesarean Section estimating (min)	Up to One hour	Yes
Secondary	Hemoglobin level (Hb)	6 hours post-operative hemoglobin level (mg/dL) estimating.	6 hours	Yes
Secondary	Maternal weight (W)	2 hours post-operative maternal weight (kg) estimating	2 hours	Yes
Secondary	Hematocrit value (Hct)	6 hours post-operative hematocrit value (%) estimating.	6 hours	Yes
Secondary	Need for blood or blood products transfusion	Need for other medical measures to arrest and manage bleeding (transfusion of blood or blood products)	Up to 6 hours	Yes
Secondary	Need for additional ecbolics	Need for other medical measures to arrest and manage bleeding if there is a uterine atony (more than five units of intravenous Syntocinon®)	Up to 6 hours	Yes
Secondary	Need for hysterectomy	Need for other surgical measures to arrest and manage bleeding (Hysterectomy)	Up to 6 hours	Yes
Secondary	Need for uterine artery ligation	Need for other surgical measures to arrest and manage bleeding (Uterine artery ligation)	Up to 6 hours	Yes
Secondary	Need for B-lynch	Need for other surgical measures to arrest and manage bleeding if there is a uterine atony (B-lynch)	Up to 6 hours	Yes
Secondary	APGAR Score	APGAR Score as index for any neonatal side effects of medications given	Up to 30 minutes	Yes
Secondary	Any sign for developing a thromboembolic disorder (Maternal)	As index for any maternal side effects of medications given	One week	Yes
Secondary	Blood pressure	Measuring maternal blood pressure (mmHg) immediately postoperative and after 2 hours postoperative.	Up to 2 hours	Yes
Secondary	Pulse rate	Measuring maternal blood puse rate (/minute) immediately postoperative and after 2 hours postoperative.	Up to 2 hours	Yes