Tranexamic Acid for Postpartum Hemorrhage
(Optimum Trial)
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18 - 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Inova Health Care Services
Must not be taking: Anti-fibrinolytics
Disqualifiers: Thromboembolic disease, Seizure disorder, Renal dysfunction, others
No Placebo Group
Prior Safety Data
Approved in 6 Jurisdictions
Trial Summary
What is the purpose of this trial?In part 1 of the study, the investigators conducted a prospective, open-label, dose finding pharmacokinetic (PK) study in 43 pregnant 3rd trimester women scheduled for non-emergent cesarean section.
The investigators administered three doses of the drug (5 mg/kg, 10 mg/kg and 15 mg/kg) in an escalating fashion by cohort with the lowest dose first. The drug was administered intravenously at the time of umbilical cord clamping for a non-emergent cesarean section. A maximum of 1 gram was administered. TXA serum levels at several time points after delivery were assayed to see if they reach the target plasma concentration of 10 microg/mL. A PK model was constructed for determining the optimal TXA dose administered at parturition.
In part 2 of the study, the investigators aim to compare PKPD endpoints using prophylactic TXA via IV and IM routes administered pre-cord clamp. The investigators will administer 1000 mg TXA within 10 minutes of skin incision via intravenous infusion (up to n=15), intravenous bolus \< 2 minutes (up to n=15) and intramuscular injection (up to n=15). The investigators will target women undergoing scheduled cesarean delivery greater than 34 weeks gestation, women undergoing vaginal delivery \> 34 weeks of gestation and morbidly obese women (BMI\>50) undergoing either a vaginal or cesarean delivery. The investigators will use advanced modeling techniques to determine time to achieve PKPD targets and duration remaining at those targets. The goal will be to determine how the optimal dose may vary if route of administration is modified. The investigators plan to enroll 45 patients in addition to the 43 that were enrolled during part 1. Our goal is to 30 participants, but the investigators will enroll 45 to account for lost to follow-up. The investigatorsalso aim to enroll 30 patients undergoing vaginal delivery and 30 morbidly obese women (BMI \> 50) undergoing either a vaginal or cesarean delivery but the investigators will enroll 45 patients for each of these groups to account for loss to follow up. In addition, the investigators will enroll 30 pregnant patients receiving no medication acting as the control group, but the investigators will enroll 45 to account for loss to follow up.
Do I need to stop my current medications to join the trial?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the drug Tranexamic Acid for postpartum hemorrhage?
Research shows that Tranexamic Acid can reduce the risk of death from bleeding in cases of postpartum hemorrhage. It is recommended by the World Health Organization as a first-line treatment for this condition, indicating its effectiveness in managing severe bleeding after childbirth.
12345Is tranexamic acid generally safe for humans?
Tranexamic acid is generally safe for humans when used correctly, as studies have shown no harmful effects on the liver, kidney, or heart. However, there have been serious safety concerns when it is mistakenly given in the wrong way during surgeries, leading to severe reactions like convulsions.
678910How is the drug tranexamic acid unique in treating postpartum hemorrhage?
Tranexamic acid is unique because it is an antifibrinolytic agent that helps reduce bleeding-related deaths when given shortly after childbirth, and it is recommended by the World Health Organization as a first-line treatment for postpartum hemorrhage. Unlike some other treatments, it is administered intravenously and is particularly effective when used within 1 to 3 hours after delivery.
511121314Eligibility Criteria
This trial is for women aged 18-50, over 34 weeks pregnant, undergoing elective cesarean or vaginal delivery. It includes morbidly obese women (BMI > 50). Participants must have normal kidney function and no history of thrombosis, liver dysfunction, seizure disorders, multiple gestations, or color vision defects.Inclusion Criteria
I am over 34 weeks pregnant and planning a vaginal birth.
I am a woman scheduled for a C-section after 34 weeks of pregnancy.
Pregnant women with normal serum creatinine (serum creatinine < 0.9)
+2 more
Exclusion Criteria
I have a genetic condition or another illness that increases my risk of blood clots.
I am a woman who has had a bleeding in the space around my brain.
I am younger than 18 or older than 50.
+8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment Part 1
Prospective, open-label, dose finding pharmacokinetic (PK) study in pregnant women scheduled for non-emergent cesarean section. TXA administered intravenously at the time of umbilical cord clamping.
1 day
1 visit (in-person)
Treatment Part 2
Comparison of PKPD endpoints using prophylactic TXA via IV and IM routes administered pre-cord clamp. TXA administered within 10 minutes of skin incision.
1 day
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment. Plasma and breast milk sampling at various time points post-administration.
10-18 hours
Multiple visits (in-person)
Participant Groups
The study tests Tranexamic acid (TXA) to prevent postpartum hemorrhage. Part one determined the optimal dose; part two compares how TXA works when given through IV or IM before cord clamping in different patient groups including a control group with no medication.
4Treatment groups
Experimental Treatment
Active Control
Group I: Vaginal DeliveryExperimental Treatment1 Intervention
Group II: Morbidly ObeseExperimental Treatment1 Intervention
Group III: Cesarean DeliveryExperimental Treatment1 Intervention
Group IV: No TXAActive Control1 Intervention
Tranexamic acid is already approved in United States, European Union, Australia, Japan for the following indications:
🇺🇸 Approved in United States as Lysteda for:
- Heavy Menstrual Bleeding
- Menstrual Disorders
- Bleeding Disorder
- Factor IX Deficiency
- Hemophilia A
- Melasma
🇪🇺 Approved in European Union as Cyklokapron for:
- Heavy Menstrual Bleeding
- Menstrual Disorders
- Bleeding Disorder
- Factor IX Deficiency
- Hemophilia A
- Melasma
- Postpartum hemorrhage
🇦🇺 Approved in Australia as Cyklokapron for:
- Heavy Menstrual Bleeding
- Menstrual Disorders
- Bleeding Disorder
- Factor IX Deficiency
- Hemophilia A
- Melasma
- Postpartum hemorrhage
🇯🇵 Approved in Japan as Nicolda for:
- Heavy Menstrual Bleeding
- Menstrual Disorders
- Bleeding Disorder
- Factor IX Deficiency
- Hemophilia A
- Melasma
- Postpartum hemorrhage
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Inova Health SystemFalls Church, VA
Inova Fairfax Medical CampusFalls Church, VA
Holy Cross HospitalSilver Spring, MD
George Washington University HospitalWashington, United States
Loading ...
Who Is Running the Clinical Trial?
Inova Health Care ServicesLead Sponsor
University of MarylandCollaborator
University of North CarolinaCollaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Collaborator
George Washington UniversityCollaborator
References
[Clinical study on the efficacy of tranexamic acid in reducing postpartum blood lose: a randomized, comparative, multicenter trial]. [2022]To study the efficacy and safety of Transamin (tranexamic acid) in reducing postpartum blood loss.
Tranexamic acid for the prevention of postpartum bleeding: Protocol for a systematic review and individual patient data meta-analysis. [2023]Tranexamic acid (TXA) reduces the risk of death and is recommended as a treatment for women with severe postpartum bleeding. There is hope that giving TXA shortly before or immediately after birth could prevent postpartum bleeding. Extending the use of TXA to prevent harmful postpartum bleeding could improve outcomes for millions of women; however we must carefully consider the balance of benefits and potential harms. This article describes the protocol for a systematic review and individual patient data (IPD) meta-analysis to assess the effectiveness and safety of TXA for preventing postpartum bleeding in all women giving birth, and to explore how the effects vary by underlying risk and other patient characteristics. Methods: We will search for prospectively registered, randomised controlled trials involving 500 patients or more assessing the effects of TXA in women giving birth. Two authors will extract data and assess risk of bias. IPD data will be sought from eligible trials. Primary outcomes will be life-threatening bleeding and thromboembolic events. We will use a one-stage model to analyse the data. Subgroup analyses will be conducted to explore whether the effectiveness and safety of TXA varies by underlying risk, type birth, maternal haemoglobin (Hb), and timing of TXA. This protocol is registered on PROSPERO (CRD42022345775). Conclusions: This systematic review and IPD meta-analysis will address important clinical questions about the effectiveness and safety of the use of TXA for the prevention of postpartum bleeding that cannot be answered reliably using aggregate data and will inform the decision of who to treat. PROSPERO registration: CRD42022345775 Keywords Anti-fibrinolytics; Tranexamic acid; childbirth; postpartum haemorrhage; meta-analysis.
Use of tranexamic acid (TXA) to reduce preterm birth and other adverse obstetrical outcomes among pregnant individuals with placenta previa: a systematic review protocol. [2023]Placenta previa is a placental implantation pathology where the placenta overlies the internal endocervical os. Placenta previa affects approximately 4 per 1000 pregnancies and increases the risk of antepartum bleeding, emergent preterm labour and emergency caesarean sections. Currently, placenta previa is managed through expectant management. Guidelines primarily revolve around the mode and timing of delivery, in-hospital admissions and surveillance. However, the methods to prolong pregnancy have not proven to be clinically effective. Tranexamic acid (TXA), an antifibrinolytic agent, is effectively used to prevent and treat postpartum haemorrhage as well as menorrhagia, with limited adverse effect, and may prove to be an effective treatment for placenta previa. The objective of this systematic review protocol is to review and synthesise the evidence of TXA use for antepartum haemorrhage in placenta previa.
Effect of tranexamic acid by baseline risk of death in acute bleeding patients: a meta-analysis of individual patient-level data from 28 333 patients. [2021]Early administration of the antifibrinolytic drug tranexamic acid reduces death from bleeding in trauma and postpartum haemorrhage. We examined how the effectiveness and safety of antifibrinolytic drugs varies by the baseline risk of death as a result of bleeding.
Tranexamic acid for the treatment of postpartum hemorrhage: a cost-effectiveness analysis. [2022]Postpartum hemorrhage is a leading cause of pregnancy-related morbidity and mortality. Recent data have demonstrated that tranexamic acid reduces death because of bleeding when used as a treatment for postpartum hemorrhage. The World Health Organization now recommends tranexamic acid as a first-line treatment for postpartum hemorrhage; however, data are not yet available on the frequency of use in the United States, where tranexamic acid is currently recognized as an adjunct treatment for postpartum hemorrhage.
Tranexamic acid at cesarean delivery: drug-error deaths. [2023]The use of tranexamic acid for postpartum hemorrhage has entered obstetrical practice globally with the evidence-based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during cesarean delivery, an important setting for severe hemorrhage. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard, and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life-saving potential of tranexamic acid is not eclipsed by drug-error mortality.
Tranexamic acid at cesarean delivery: drug-error deaths. [2023]The use of tranexamic acid for postpartum hemorrhage has entered obstetrical practice globally with the evidence-based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during cesarean delivery, an important setting for severe hemorrhage. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard, and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life-saving potential of tranexamic acid is not eclipsed by drug-error mortality.
Tranexamic acid at cesarean delivery: drug-error deaths. [2022]The use of tranexamic acid for postpartum hemorrhage has entered obstetrical practice globally with the evidence-based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during cesarean delivery, an important setting for severe hemorrhage. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard, and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life-saving potential of tranexamic acid is not eclipsed by drug-error mortality.
Tranexamic acid at cesarean delivery: Drug-error deaths. [2022]The use of tranexamic acid for postpartum hemorrhage has entered obstetrical practice globally with the evidence-based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during cesarean delivery, an important setting for severe hemorrhage. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard, and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life-saving potential of tranexamic acid is not eclipsed by drug-error mortality.
Tranexamic acid in control of haemorrhage after dental extraction in haemophilia and Christmas disease. [2019]In a double-blind trial tranexamic acid (AMCA, Cyclokapron), 1 g three times a day for five days, significantly reduced blood loss and transfusion requirements after dental extraction in patients with haemophilia and Christmas disease. No side effects were seen in either group of patients. Screening tests showed no toxic action of tranexamic acid on the liver, kidney, or heart.
Tranexamic acid for childbirth: why, when, and for whom. [2020]Introduction: Postpartum hemorrhage (PPH) is a major cause of maternal death and severe maternal morbidity after childbirth. Areas covered: Tranexamic acid, an antifibrinolytic agent, reduces bleeding-related mortality in women with PPH, especially when administered shortly after delivery, and is consequently recommended in this situation (1g intravenously with a second dose of 1 g if bleeding continues), even in high income countries where the magnitude of the effect of tranexamic is uncertain. Expert opinion: Pharmacovigilance surveys are warranted in high income areas to ensure that this new policy for the treatment of PPH is not associated to rare but severe adverse events such as renal failure. The evidence remains insufficient to recommend the universal use of tranexamic acid for prevention of postpartum hemorrhage after both vaginal and cesarean deliveries.
Tranexamic acid versus misoprostol for management of postpartum hemorrhage: A systematic review and meta-analysis of randomized controlled trials. [2023]To conduct the first-ever systematic review and meta-analysis of randomized controlled trials (RCTs) on the antihemorrhagic utility and safety of tranexamic acid (TXA) versus misoprostol for management (prevention and/or treatment) of postpartum hemorrhage (PPH).
Does tranexamic acid reduce mortality in women with postpartum hemorrhage? [2020]When used in conjunction with the standard of care, 1 g intravenous (IV) tranexamic acid given 1 to 3 hours after delivery is associated with a significant reduction in maternal mortality from postpartum hemorrhage (PPH) (strength of recommendation: A, randomized controlled trial [RCT] and Cochrane review).
Does tranexamic acid prevent postpartum haemorrhage? A systematic review of randomised controlled trials. [2021]Postpartum haemorrhage is the leading cause of maternal mortality. Tranexamic acid (TXA) reduces surgical haemorrhage and the risk of death in bleeding trauma patients.