Prevention of Postpartum Hemorrhage With TXA

Overview

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.

Full Title of Study: “Prevention of Postpartum Hemorrhage With Tranexamic Acid (TXA)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Prevention
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 2019

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).

Interventions

  • 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

Arms, Groups and Cohorts

  • Experimental: ProphylacticTranexamic Acid
    • Once consented, patients to receive 1000mg/10ml normal saline infusion of TXA with the delivery of the infant’s anterior shoulder.

Clinical Trial Outcome Measures

Primary Measures

  • Incidence of postpartum hemorrhage
    • Time Frame: Up to six weeks from date of delivery
    • Postpartum hemorrhage

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 54 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • United States Naval Medical Center, San Diego
  • Provider of Information About this Clinical Study
    • Principal Investigator: Maureen Farrell, Program Director, Obstetrics & Gynecology Residency – United States Naval Medical Center, San Diego
  • Overall Official(s)
    • Maureen E Farrell, MD, Principal Investigator, United States Naval Medical Center, San Diego,CA
  • Overall Contact(s)
    • Salvador I Doria, 619-532-9927, salvador.i.doria.civ@mail.mil

References

Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB, Daniels J, Gülmezoglu 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. Review.

Zelop CM. Postpartum hemorrhage: becoming more evidence-based. Obstet Gynecol. 2011 Jan;117(1):3-5. doi: 10.1097/AOG.0b013e318202ec9a.

World Health Organization (WHO) Recommendations for the Prevention and Treatment of Postpartum Haemorrhage.Geneva: World Health Organization; 2012.

Citations Reporting on Results

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.

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. Review.

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. Review.

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.

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. Review.

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.

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.

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.

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