Use of TXA to Prevent Postpartum Hemorrhage

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Post Partum Hemorrhage

Intervention / Treatment
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* Drug: TXA (1g)
* Drug: Placebo (0.9% saline)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TXA (1g)<br>For vaginal, TXA (1g) will be administered upon delivery of the anterior shoulder. For c-section, TXA (1g) will be administered when the obstetrician begins to cleanse the incision site | Drug: TXA (1g)<br>* 1 gram of TXA (10 mL) diluted into 0.9% saline, 50 ml mini-bag (a total of 60 mL)<br>* Other names: TXA;|
| Placebo Comparator: Placebo (0.9% saline)<br>For vaginal, placebo (0.9% saline) will be administered upon delivery of the anterior shoulder. For c-section, placebo (0.9% saline) will be administered when the obstetrician begins to cleanse the incision site | Drug: Placebo (0.9% saline)<br>* 0.9% saline (10 mL), diluted into 0.9% saline, 50 ml mini-bag (a total of 60 mL)<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients receiving study intervention | Proportion of patients receiving study intervention (IP) after randomization | At time of delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of study to recruit 58 participants | Total time required to recruit and randomize 58 patients | Up to 4 months | 
| Proportion of budget needed to recruit 58 participants | Cost required to recruit and randomize 58 patients | Up to 4 months | 
| 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 | 
| Incidence of PPH in study participants | Incidence of PPH or severe PPH in study participants | Up to 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post partum hemorrhage, Tranexamic acid, Spontaneous vaginal delivery, C-section