Use of TXA to Prevent Postpartum Hemorrhage

Post Partum Hemorrhage Clinical Trial

— TAPPH-1  

Official title:

Prophylactic Use of Tranexamic Acid for Preventing Postpartum Hemorrhage: A Randomized, Double-blinded, Placebo-controlled Pilot Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03069859
• Other study ID #: 418-2016
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 6, 2018
• Est. completion date: December 2022

Study information

• Verified date: September 2022
• Source: Sunnybrook Health Sciences Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Postpartum hemorrhage (PPH) occurs in up to one in ten deliveries worldwide and is the leading cause of maternal morbidity and mortality. In developing countries 30% of women develop PPH because access to a number of treatments is not readily available. Interestingly, the rate of PPH and consequently of maternal morbidity has increased significantly even in developed nations, such as Canada, over the past decades. This rate is also increasing amongst parturients in Ontario. Unfortunately, few effective preventative treatments exist. Antifibrinolytic drugs are routinely used to reduce bleeding and the requirement for blood transfusions in a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug is tranexamic acid (TXA). TXA is safe, affordable, with very few side effects. The World Health Organization recommended that TXA be used to reduce blood loss in several conditions, including in patients with established PPH refractory to conventional therapy.However, little is known about the prophylactic use of TXA to prevent PPH.

Description:

This pragmatic, singlecentered, doubleblinded, randomized-controlled pilot trial will assess the feasibility of administering a prophylactic dose of TXA to prevent the onset of PPH amongst parturients undergoing cesarean section and spontaneous vaginal delivery. Our primary outcome will be to determine the proportion of patients who receive the investigational product successfully. Our secondary outcomes include 1) additional feasibility endpoints; 2) safety endpoints and 3) various other clinical endpoints. These clinical endpoints include a) incidence of PPH (and severe PPH); b) total number of transfusions; c) use of uterotonic drugs; and d) hospital length of stay. The investigators anticipate that TXA can be safely administered to parturients prior to delivery. The investigators also believe it will be an effective prophylactic therapy for PPH and will reduce its severity and associated morbidity. Results from this trial will be used to design and conduct a larger multicentered trial, powered to assess the outcomes of interest. Furthermore, this prophylactic use of TXA for PPH could improve outcomes of parturients not only in Ontario but worldwide where effective management of PPH remains an ongoing challenge.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 31
• Est. completion date: December 2022
• Est. primary completion date: December 1, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years of age or older
• Singleton pregnancy
• Confirmed pregnancy
• Gestational age >32^0/7 weeks

Exclusion Criteria:

• Lack of patient consent
• Multiple pregnancy
• History of eclampsia or preeclampsia in current pregnancy
• Imminent Delivery as suspected by any RN or MD involved in delivery care
• History of cardiovascular complications:
• Coronary artery disease or myocardial infarction
• Repaired or unrepaired congenital heart disease
• Vascular disease(s)
• Severe unstable arrhythmia (e.g. Rapid atrial fibrillation, paroxysmal fibrillation, atrial flutter, etc.)
• Congestive heart failure
• Contraindication to TXA:
• History of venous thromboembolism
• Active thromboembolic disease
• High risk of thrombosis (e.g. Factor V Leiden or Protein C deficiency)
• Acquired disturbances of colour vision
• Allergy to TXA
• History of seizure disorder
• Pre-existing hematuria
• History of renal insufficiency
• Unlikely to comply with follow-up (e.g. no fixed address, plans to move out of town)
• Prisoner status

Related Conditions & MeSH terms

• Hemorrhage
• Post Partum Hemorrhage
• Postpartum Hemorrhage

Intervention

Drug:
• TXA (1g)
1 gram of TXA (10 mL) diluted into 0.9% saline, 50 ml mini-bag (a total of 60 mL)
• Placebo (0.9% saline)
0.9% saline (10 mL), diluted into 0.9% saline, 50 ml mini-bag (a total of 60 mL)

Locations

Country	Name	City	State
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre

Country where clinical trial is conducted

Canada, 

References & Publications (31)

Alam A, Choi S. Prophylactic Use of Tranexamic Acid for Postpartum Bleeding Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Transfus Med Rev. 2015 Oct;29(4):231-41. doi: 10.1016/j.tmrv.2015.07.002. Epub 2015 Jul 17. Review. — View Citation

American College of Obstetricians and Gynecologists. ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists Number 76, October 2006: postpartum hemorrhage. Obstet Gynecol. 2006 Oct;108(4):1039-47. — View Citation

Calvert C, Thomas SL, Ronsmans C, Wagner KS, Adler AJ, Filippi V. Identifying regional variation in the prevalence of postpartum haemorrhage: a systematic review and meta-analysis. PLoS One. 2012;7(7):e41114. doi: 10.1371/journal.pone.0041114. Epub 2012 Jul 23. Review. — View Citation

Carroli G, Cuesta C, Abalos E, Gulmezoglu AM. Epidemiology of postpartum haemorrhage: a systematic review. Best Pract Res Clin Obstet Gynaecol. 2008 Dec;22(6):999-1012. doi: 10.1016/j.bpobgyn.2008.08.004. Epub 2008 Sep 25. Review. — 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

Deneux-Tharaux C, Sentilhes L, Maillard F, Closset E, Vardon D, Lepercq J, Goffinet F. Effect of routine controlled cord traction as part of the active management of the third stage of labour on postpartum haemorrhage: multicentre randomised controlled trial (TRACOR). BMJ. 2013 Mar 28;346:f1541. doi: 10.1136/bmj.f1541. Erratum in: BMJ. 2013;346:f2542. BMJ.2013;347:f6619. — View Citation

Elwatidy S, Jamjoom Z, Elgamal E, Zakaria A, Turkistani A, El-Dawlatly A. Efficacy and safety of prophylactic large dose of tranexamic acid in spine surgery: a prospective, randomized, double-blind, placebo-controlled study. Spine (Phila Pa 1976). 2008 Nov 15;33(24):2577-80. doi: 10.1097/BRS.0b013e318188b9c5. — View Citation

Faraoni D, Willems A, Melot C, De Hert S, Van der Linden P. Efficacy of tranexamic acid in paediatric cardiac surgery: a systematic review and meta-analysis. Eur J Cardiothorac Surg. 2012 Nov;42(5):781-6. doi: 10.1093/ejcts/ezs127. Epub 2012 Apr 24. Review. — View Citation

Ford JB, Roberts CL, Simpson JM, Vaughan J, Cameron CA. Increased postpartum hemorrhage rates in Australia. Int J Gynaecol Obstet. 2007 Sep;98(3):237-43. Epub 2007 May 4. — View Citation

Gilad O, Merlob P, Stahl B, Klinger G. Outcome following tranexamic acid exposure during breastfeeding. Breastfeed Med. 2014 Oct;9(8):407-10. doi: 10.1089/bfm.2014.0027. Epub 2014 Jul 15. — View Citation

Grassin-Delyle S, Tremey B, Abe E, Fischler M, Alvarez JC, Devillier P, Urien S. Population pharmacokinetics of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass. Br J Anaesth. 2013 Dec;111(6):916-24. doi: 10.1093/bja/aet255. Epub 2013 Jul 23. — View Citation

Guerriero C, Cairns J, Perel P, Shakur H, Roberts I; CRASH 2 trial collaborators. Cost-effectiveness analysis of administering tranexamic acid to bleeding trauma patients using evidence from the CRASH-2 trial. PLoS One. 2011 May 3;6(5):e18987. doi: 10.1371/journal.pone.0018987. — View Citation

Hoylaerts M, Lijnen HR, Collen D. Studies on the mechanism of the antifibrinolytic action of tranexamic acid. Biochim Biophys Acta. 1981 Feb 18;673(1):75-85. — View Citation

Joseph KS, Rouleau J, Kramer MS, Young DC, Liston RM, Baskett TF; Maternal Health Study Group of the Canadian Perinatal Surveillance System. Investigation of an increase in postpartum haemorrhage in Canada. BJOG. 2007 Jun;114(6):751-9. — View Citation

Ker K, Edwards P, Perel P, Shakur H, Roberts I. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis. BMJ. 2012 May 17;344:e3054. doi: 10.1136/bmj.e3054. Review. — View Citation

Kirigia JM, Oluwole D, Mwabu GM, Gatwiri D, Kainyu LH. Effects of maternal mortality on gross domestic product (GDP) in the WHO African region. Afr J Health Sci. 2006 Jan-Jun;13(1-2):86-95. — View Citation

Knight M, Callaghan WM, Berg C, Alexander S, Bouvier-Colle MH, Ford JB, Joseph KS, Lewis G, Liston RM, Roberts CL, Oats J, Walker J. Trends in postpartum hemorrhage in high resource countries: a review and recommendations from the International Postpartum Hemorrhage Collaborative Group. BMC Pregnancy Childbirth. 2009 Nov 27;9:55. doi: 10.1186/1471-2393-9-55. Review. — View Citation

Mehrabadi A, Hutcheon JA, Lee L, Kramer MS, Liston RM, Joseph KS. Epidemiological investigation of a temporal increase in atonic postpartum haemorrhage: a population-based retrospective cohort study. BJOG. 2013 Jun;120(7):853-62. doi: 10.1111/1471-0528.12149. Epub 2013 Mar 6. — View Citation

Mehrabadi A, Hutcheon JA, Lee L, Liston RM, Joseph KS. Trends in postpartum hemorrhage from 2000 to 2009: a population-based study. BMC Pregnancy Childbirth. 2012 Oct 11;12:108. doi: 10.1186/1471-2393-12-108. — View Citation

Mehrabadi A, Liu S, Bartholomew S, Hutcheon JA, Kramer MS, Liston RM, Joseph KS; Maternal Health Study Group of the Canadian Perinatal Surveillance System (Public Health Agency of Canada). Temporal trends in postpartum hemorrhage and severe postpartum hemorrhage in Canada from 2003 to 2010. J Obstet Gynaecol Can. 2014 Jan;36(1):21-33. doi: 10.1016/S1701-2163(15)30680-0. Erratum in: J Obstet Gynaecol Can. 2014 Mar;36(3):207. — View Citation

Mpemba F, Kampo S, Zhang X. Towards 2015: post-partum haemorrhage in sub-Saharan Africa still on the rise. J Clin Nurs. 2014 Mar;23(5-6):774-83. doi: 10.1111/jocn.12126. Epub 2013 Mar 8. Review. — View Citation

Nilsson IM. Clinical pharmacology of aminocaproic and tranexamic acids. J Clin Pathol Suppl (R Coll Pathol). 1980;14:41-7. Review. — View Citation

Novikova N, Hofmeyr GJ. Tranexamic acid for preventing postpartum haemorrhage. Cochrane Database Syst Rev. 2010 Jul 7;(7):CD007872. doi: 10.1002/14651858.CD007872.pub2. Review. Update in: Cochrane Database Syst Rev. 2015;6:CD007872. — View Citation

Perel P, Ker K, Morales Uribe CH, Roberts I. Tranexamic acid for reducing mortality in emergency and urgent surgery. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD010245. doi: 10.1002/14651858.CD010245.pub2. Review. — View Citation

Sentilhes L, Daniel V, Darsonval A, Deruelle P, Vardon D, Perrotin F, Le Ray C, Senat MV, Winer N, Maillard F, Deneux-Tharaux C. Study protocol. TRAAP - TRAnexamic Acid for Preventing postpartum hemorrhage after vaginal delivery: a multicenter randomized, double-blind, placebo-controlled trial. BMC Pregnancy Childbirth. 2015 Jun 14;15:135. doi: 10.1186/s12884-015-0573-5. — 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

Shakur H, Elbourne D, Gülmezoglu M, Alfirevic Z, Ronsmans C, Allen E, Roberts I. The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial. Trials. 2010 Apr 16;11:40. doi: 10.1186/1745-6215-11-40. — View Citation

Shimizu K, Toda Y, Iwasaki T, Takeuchi M, Morimatsu H, Egi M, Suemori T, Suzuki S, Morita K, Sano S. Effect of tranexamic acid on blood loss in pediatric cardiac surgery: a randomized trial. J Anesth. 2011 Dec;25(6):823-30. doi: 10.1007/s00540-011-1235-z. Epub 2011 Sep 24. — 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

Tan J, Chen H, Liu Q, Chen C, Huang W. A meta-analysis of the effectiveness and safety of using tranexamic acid in primary unilateral total knee arthroplasty. J Surg Res. 2013 Oct;184(2):880-7. doi: 10.1016/j.jss.2013.03.099. Epub 2013 Apr 25. — View Citation

Wesley MC, Pereira LM, Scharp LA, Emani SM, McGowan FX Jr, DiNardo JA. Pharmacokinetics of tranexamic acid in neonates, infants, and children undergoing cardiac surgery with cardiopulmonary bypass. Anesthesiology. 2015 Apr;122(4):746-58. doi: 10.1097/ALN.0000000000000570. — View Citation

* Note: There are 31 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients receiving study intervention	Proportion of patients receiving study intervention (IP) after randomization	At time of delivery
Secondary	Duration of study to recruit 58 participants	Total time required to recruit and randomize 58 patients	Up to 4 months
Secondary	Proportion of budget needed to recruit 58 participants	Cost required to recruit and randomize 58 patients	Up to 4 months
Secondary	Composite number of clinical events	Clinical events (adverse events) such as thrombotic complications, acute renal failure, seizure, not related to a diagnosis of preeclampsia or eclampsia, receipt of mechanical ventilation and ICU admission, death, minor side effects, thrombotic complications (as listed above) in the newborn, rates of acute renal failure in the newborn, seizures in the newborn at 24-48 hours will be documented to assess for the overall safety of this trial	At 6 week (+/- 14 days) and 12 week (+/- 14 days) follow-ups assessments
Secondary	Incidence of PPH in study participants	Incidence of PPH or severe PPH in study participants	Up to 4 months