Prevention of Postpartum Hemorrhage With TXA (TXA)

Prevention of Postpartum Hemorrhage With Tranexamic Acid (TXA)

Hemorrhage remains the leading cause of maternal death worldwide. Tranexamic acid has been shown to reduce rates of hemorrhage when given prophylactically prior to cesarean delivery. It has also been shown to be an effective treatment in response to hemorrhage after a vaginal delivery. The aim of this study is to assess the impact of TXA on hemorrhage rates when given prophylactically prior to all deliveries.

Study Overview

• Status: Withdrawn
• Conditions: Postpartum Hemorrhage
• Intervention / Treatment: Drug: Tranexamic Acid 1000 mg/10ml normal saline infusion

Detailed Description

Hemorrhage remains the leading cause of maternal mortality worldwide. In a 2014 systematic analysis of the causes of maternal death, the World Health Organization (WHO) noted that even in the face of interventions developed to actively manage the third stage of labor, 27.1% of maternal deaths were directly attributable to excessive blood loss.

Risk factors for postpartum hemorrhage (PPH) have been identified, but the majority of cases occur in low risk women. As such, the routine use of oxytocin in the third stage of labor is recommended in all women and has been well documented to reduce the risk of excessive blood loss. Uterotonics such as methylergonovine, 15-methyl PGF2α and misoprostol have shown to be particularly useful adjuncts as decreased uterine tone is the most common etiology of blood loss. More recently, tranexamic acid (TXA) has been shown to be efficacious in the prevention of postpartum hemorrhage in certain cohorts.

Tranexamic acid exerts its effect through the binding of plasmin and subsequent inhibition of fibrin degradation. It is regarded as pregnancy category B by the Food and Drug Administration (FDA).

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Salvador I Doria; Phone Number: 619-532-9927; Email: salvador.i.doria.civ@mail.mil
• Study Contact Backup: Name: Geri P Hollinger; Phone Number: 619-532-9416; Email: geri.p.hollinger.civ@mail.mil

Study Locations

• United States
  • California
    • San Diego, California, United States, 92134
      • Navy Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 54 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Pregnant female presenting to Navy Medical Center San Diego for delivery
• Able to speak and understand English
• Planning to deliver at NMCSD

Exclusion Criteria:

• Age less than 18 years
• Unable to speak or understand English
• Not planning to deliver at NMCSD
• Planned cesarean hysterectomy
• Current anticoagulant use
• Current subarachnoid hemorrhage
• Any active/current intravascular clotting (i.e. venous thromboembolic events)
• Patients with a hypersensitivity to TXA or any of the ingredients
• Personal history of venous or arterial thrombotic events
• Conditions that predispose patients to thromboembolic events (e.g. thrombophilias, autoimmune diseases such as lupus, active cancer, congestive heart failure, family history of thrombosis in a first degree relative at age < 30 years) due to increased risk of thrombosis
• Patients taking factor IX complex concentrates or anti-inhibitor coagulant concentrates (e.g. FEIBA NF)
• Eclampsia or seizure disorder because the use of tranexamic acid has been associated with postoperative seizures
• Patients with a baseline creatinine 1.2 or higher, history of renal insufficiency, or renal disease because of the risk of toxicity in patients with preexisting disease
• Patients with frank hematuria because ureteral obstruction due to clot formation has been reported in patients with upper urinary tract bleeding who were treated with tranexamic acid
• Patients with active or history of retinal diseases as cases of central retinal artery and central retinal vein obstruction have been reported in patients treated with intravenous tranexamic acid
• Patients with acquired defective color vision

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ProphylacticTranexamic Acid; Once consented, patients to receive 1000mg/10ml normal saline infusion of TXA with the delivery of the infant's anterior shoulder.	Drug: Tranexamic Acid 1000 mg/10ml normal saline infusion; Infusion of Tranexamic Acid (Cyklokapron) to all consented women with the delivery of the anterior shoulder of the infant; Other Names: Cyklokapron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of postpartum hemorrhage	Postpartum hemorrhage	Up to six weeks from date of delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postpartum blood loss	Estimated blood loss (EBL)	Up to six weeks from date of delivery
Percent decrease in hematocrit	Hematocrit percentage	6 hours after hemorrhage event and as clinically indicated up to six weeks from date of delivery
Number of units of packed red blood cells transfused	Number of units of packed red blood cells transfused	Up to six weeks from date of delivery
Number of units of platelets transfused	Number of units of platelets transfused	Up to six weeks from date of delivery
Number of units of fresh frozen plasma transfused	Number of units of fresh frozen plasma transfused	Up to six weeks from date of delivery
Number of units of cryoprecipitate transfused	Number of units of cryoprecipitate transfused	Up to six weeks from date of delivery
Amount of methylergonovine administered	Amount of methylergonovine administered	Up to six weeks from date of delivery
Amount of 15-methyl prostaglandin F2(PGF2) administered	Amount of 15-methyl prostaglandin F2(PGF2) administered	Up to six weeks from date of delivery
Amount of misoprostol administered	Amount of misoprostol administered	Up to six weeks from date of delivery
Amount of oxytocin administered	Amount of oxytocin administered	Up to six weeks from date of delivery
Exploratory laparotomy following vaginal delivery due to hemorrhage	Exploratory laparotomy, no hysterectomy	Up to six weeks from date of delivery
Exploratory laparotomy following cesarean delivery due to hemorrhage	Exploratory laparotomy, no hysterectomy	Up to six weeks from date of delivery
Hysterectomy	Number of hysterectomies performed as a result of postpartum hemorrhage	Up to six weeks from date of delivery
Intensive Care Unit (ICU) admission	Number of subjects admitted to Intensive Care Unit diagnosed with postpartum hemorrhage	Up to six weeks from date of delivery
Maternal thromboembolic events	Incidence of maternal thromboembolic events	up to six weeks from date of delivery
Diagnosis of intraventricular hemorrhage in the neonate	Neonatal outcome intraventricular hemorrhage	Up to six weeks from date of delivery
Diagnosis of anemia in the neonate	Neonatal outcome anemia	Up to six weeks from date of delivery
Diagnosis of disseminated intravascular coagulation (DIC) in the neonate	Neonatal outcome DIC	Up to six weeks from date of delivery
Diagnosis of neonatal sepsis	Neonatal outcome sepsis	Up to six weeks from date of delivery
Diagnosis of hypoxic-ischemic encephalopathy (HIE) in the neonate	Neonatal outcome HIE	Up to six weeks from date of delivery
Diagnosis of a seizure disorder in the neonate	Neonatal outcome seizure disorder	Up to six weeks from date of delivery
Diagnosis of arrhythmia in the neonate	Neonatal outcome arrhythmia	Up to six weeks from date of delivery
Diagnosis of heart failure in the neonate	Neonatal outcome heart failure	Up to six weeks from date of delivery
Diagnosis of renal failure in the neonate	Neonatal outcome renal failure	Up to six weeks from date of delivery
Diagnosis of hepatic failure in the neonate	Neonatal outcome hepatic failure	Up to six weeks from date of delivery
Diagnosis of thromboembolic events in the neonate	Neonatal outcome thromboembolic event	Up to six weeks from date of delivery
Maternal mortality	Incidence of maternal mortality	Up to six weeks from date of delivery
Additional tranexamic acid administered	Additional tranexamic acid administered	Up to six weeks from date of delivery
Rate of Bakri/balloon tamponade use	Bakri/balloon tamponade use	Up to six weeks from date of delivery

Collaborators and Investigators

• Sponsor: United States Naval Medical Center, San Diego
• Investigators: Principal Investigator: Maureen E Farrell, MD, United States Naval Medical Center, San Diego,CA

Publications and helpful links

General Publications

• Say L, Chou D, Gemmill A, Tuncalp O, Moller AB, Daniels J, Gulmezoglu AM, Temmerman M, Alkema L. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014 Jun;2(6):e323-33. doi: 10.1016/S2214-109X(14)70227-X. Epub 2014 May 5.
• WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet. 2017 May 27;389(10084):2105-2116. doi: 10.1016/S0140-6736(17)30638-4. Epub 2017 Apr 26. Erratum In: Lancet. 2017 May 27;389(10084):2104.
• Zelop CM. Postpartum hemorrhage: becoming more evidence-based. Obstet Gynecol. 2011 Jan;117(1):3-5. doi: 10.1097/AOG.0b013e318202ec9a. No abstract available.
• WHO Recommendations for the Prevention and Treatment of Postpartum Haemorrhage. Geneva: World Health Organization; 2012. Available from http://www.ncbi.nlm.nih.gov/books/NBK131942/
• 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.
• Novikova N, Hofmeyr GJ, Cluver C. Tranexamic acid for preventing postpartum haemorrhage. Cochrane Database Syst Rev. 2015 Jun 16;(6):CD007872. doi: 10.1002/14651858.CD007872.pub3.
• Wang HY, Hong SK, Duan Y, Yin HM. Tranexamic acid and blood loss during and after cesarean section: a meta-analysis. J Perinatol. 2015 Oct;35(10):818-25. doi: 10.1038/jp.2015.93. Epub 2015 Jul 30.
• 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.
• Ker K, Shakur H, Roberts I. Does tranexamic acid prevent postpartum haemorrhage? A systematic review of randomised controlled trials. BJOG. 2016 Oct;123(11):1745-52. doi: 10.1111/1471-0528.14267. Epub 2016 Aug 24.
• 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, Mejia-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.
• Bouet PE, Ruiz V, Legendre G, Gillard P, Descamps P, Sentilhes L. Policy of high-dose tranexamic acid for treating postpartum hemorrhage after vaginal delivery. J Matern Fetal Neonatal Med. 2016;29(10):1617-22. doi: 10.3109/14767058.2015.1056731. Epub 2015 Jun 29.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2018
• Primary Completion (Estimated): June 1, 2019
• Study Completion (Estimated): September 1, 2019

Study Registration Dates

• First Submitted: October 10, 2017
• First Submitted That Met QC Criteria: October 25, 2017
• First Posted (Actual): October 31, 2017

Study Record Updates

• Last Update Posted (Estimated): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Hemorrhage; Tranexamic acid (TXA); Estimated Blood Loss (EBL)
• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hemorrhage; Postpartum Hemorrhage; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: NMCSD.2017.0034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No