Clinical trial NCT03287336: Prevention of Postpartum Hemorrhage With Tranexamic Acid
Official title: Prevention of Postpartum Hemorrhage: Identifying Pregnant Women at Risk and Determining the Safe and Effective Use of Tranexamic Acid Using State-of-the-art Pharmacokinetic/Pharmacodynamics Modeling
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Postpartum Hemorrhage
Keywords: tranexamic acid
postpartum hemorrhage
Lead sponsor: George Washington University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2017-09-19
Enrollment: 43
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Three doses of Tranexamic acid (5 mg/kg, 10 mg/kg, and 15 mg/kg) will be used in a dose escalation fashion by cohort with the lowest dose first.
Primary purpose: PREVENTION

Brief summary: Postpartum hemorrhage is a significant contributor to maternal morbidity and mortality and is worldwide. TXA has recently been proven to reduce mortality when given to women in setting of diagnosed PPH. US obstetricians and anesthesiologists are hesitant to use TXA in the peripartum period especially for prevention of PPH due to uncertainty of an optimal dose and safety profile. The purpose of this study is to characterize the pharmacokinetics of TXA when given prophylactically at time of delivery. In addition investigators will determine the pharmacodynamics of TXA in the peripartum period.

Detailed description: Conduct a prospective, open-label, dose finding PK study in 30 pregnant 3rd trimester women scheduled for non-emergent cesarean section who are at risk for hemorrhage. Three doses of the drug will be administered in an escalating fashion by cohort with the lowest dose first. A maximum of 1 gram will be administered. TXA serum levels at several time points after delivery will be assayed. A PK model will be constructed for determining the optimal TXA dose administered at parturition.

Eligibility criteria: Inclusion Criteria:

* Women who are undergoing medically indicated cesarean section at greater than 34+0 weeks gestation or women undergoing elective cesarean section at 39+0 weeks gestation in accordance with recommendations from the American Congress of Obstetricians and Gynecologists
* Pregnant women with normal serum creatinine (serum creatinine \< 0.9)
* Women between the ages of 18 and 50 years old

Exclusion Criteria:

* Patients younger than 18 or older than 50
* women with active thrombotic or thromboembolic disease
* Women with a history of arterial or venous thromboembolic event
* Women with inherited thrombophilia or preexisting conditions that predisposes them to thromboembolic events (i.e. lupus, antiphospholipid syndrome)
* Women with a subarachnoid hemorrhage
* Women with acquired defective color vision
* history of seizure disorder
* known renal dysfunction
* multiple gestations (Twin or triplet pregnancies)
* Hypersensitivity to Tranexamic acid or anti-fibrinolytic therapy
* History of liver dysfunction

Primary outcomes:
measure: PK Model Parameter Estimates
timeFrame: Different time points ranging from surgery (T0) to 1 day postpartum.
measure: Pharmacodynamics of Tranexamic Acid
timeFrame: Different time points ranging from surgery (T0) to 1 day postpartum.
Secondary outcomes:
measure: Estimated Blood Loss
timeFrame: During surgery
measure: Safety Parameters
timeFrame: During surgery, after surgery while in hospital, 2 weeks and 6 weeks postpartum
Other outcomes:
Locations:
city: Washington
country: United States
facility: James Slota
state: District of Columbia
Study officials:
affiliation: George Washington University
name: Homa Ahmadzia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ahmadzia HK, Luban NLC, Li S, Guo D, Miszta A, Gobburu JVS, Berger JS, James AH, Wolberg AS, van den Anker J. Optimal use of intravenous tranexamic acid for hemorrhage prevention in pregnant women. Am J Obstet Gynecol. 2021 Jul;225(1):85.e1-85.e11. doi: 10.1016/j.ajog.2020.11.035. Epub 2020 Nov 26.