TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery

Study Overview
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Brief Summary
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The aim is to assess the impact of tranexamic acid (TXA) for preventing postpartum hemorrhage (PPH) following a cesarean section (CS).

Detailed Description
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Regarding the prevention of PPH, recent randomized controlled trials (RCTs) of unclear quality have suggested that TXA may reduce blood loss and maternal morbidity, while a Cochrane Collaboration review has concluded, that TXA (in addition to uterotonic medications) decreases postpartum blood loss and prevents PPH and blood transfusions following vaginal birth and CS in women at low risk of PPH based on studies of mixed quality. Further investigations are needed on efficacy and safety of this regimen for preventing PPH. Treatment, that is a 10-mL blinded vial of the study drug (either 1g TXA or placebo according to the randomization sequence), will be administered intravenously to the participant women during the third stage of labor of cesarean delivery. The follow-up visit will take place in the postpartum ward of the maternity unit, on D2 postpartum. This stage will include a venous blood sample to measure plasma concentrations of Hb and Ht, urea and creatinemia, prothrombin time (PT), active prothrombin time (aPTT), aspartate and alanine transaminase, total bilirubin and fibrinogen, and the completion of a self-questionnaire about satisfaction by the women, as well as the assessment of the adverse events. At 8 weeks postpartum, a self-questionnaire assessing psychological status and well-being will be sent to the women. At 12 weeks postpartum, all participants will be contacted by phone to assess the incidence of thrombotic and any other significant events.

Official Title
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TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery :a Multicenter Randomised, Double Blind Placebo Controlled Trial (TRAAP2)

Conditions
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Postpartum Hemorrhage

Intervention / Treatment
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* Drug: Tranexamic Acid Injectable Solution
* Drug: Sodium Chloride 0.9%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: : adult women admitted for a cesarean delivery before or during labor, at a term ≥ 34 weeks, hemoglobin level at the last blood sample >9g/dl, available blood test for Hb and Ht within one week before caesarean delivery, informed signed consent Exclusion Criteria: previous thrombotic event or preexisting pro-thrombotic disease, epileptic state or history of seizures, presence of any chronic or active cardiovascular disease outside hypertension, any chronic or active renal disease and chronic or active liver disease at risk thrombotic or hemorrhagic, autoimmune disease, sickle cell disease, placenta praevia, placenta accreta/increta/percreta, abruption placentae, eclampsia, HELLP syndrome, significant hemorrhage before cesarean section in utero fetal death, administration of low-molecular-weight heparin or antiplatelet agents during the week before delivery, planned general anesthesia, hypersensitivity to tranexamic acid or concentrated hydrochloric acid, instrumental extraction failure, multiple pregnancy with vaginal delivery of the first child, poor understanding of the French language.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tranexamic acid<br>intravenous administration of 10-mL of tranexamic acid (EXACYL® 1 g/10 ml I.V., solution injectable) | Drug: Tranexamic Acid Injectable Solution<br>* After the routine and prophylactic administration of a uterotonic , the intervention will be the IV administration of a 10-ml blinded ampoule of the study drug (either TXA or placebo according to the randomisation sequence) to the woman within 3 minutes after birth, slowly (over 30-60 seconds), once the cord has been clamped.<br>|
| Placebo Comparator: Chloride solution<br>sodium intravenous administration of 10-mL of chloride solution (0.9% -10mL). | Drug: Sodium Chloride 0.9%<br>* After a routine and prophylactic administration of a uterotonic , the intervention will be the IV administration of a 10-ml blinded ampoule of the study drug (either TXA or placebo according to the randomisation sequence) to the patient within 3 minutes afterbirth), slowly (over 30-60 seconds), once the cord has been clamped.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| postpartum hemorrhage | Incidence of PPH defined by a calculated blood loss > 1000mL [Calculated estimated blood loss = estimated blood volume × (preoperative Ht - postoperative Ht)/preoperative Ht (where estimated blood volume (mL) = weight (Kg) × 85)] or red blood cell transfusion up to day 2 postpartum. Preoperative Ht will be the most recent Ht within one week before delivery. Postoperative Ht will be measured at D2 | day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean calculated blood loss > 500mL |  | day 2 | 
| mean calculated blood loss > 1500mL |  | day 2 | 
| total mean calculated blood loss |  | day 2 | 
| mean gravimetrically estimated blood loss | by measuring the suction volume and swab weight; proportion of women requiring supplementary uterotonic treatment including sulprostone | 6 hours | 
| incidence of postpartum transfusion |  | day 2 | 
| Mean or median number of units of red blood cells transfused |  | day 2 | 
| incidence of arterial embolisation or emergency surgery for PPH |  | 3 months | 
| mean peripartum change in haemoglobin | difference between the most recent Hb within one week before delivery and at day 2 postpartum | day 2 | 
| mean peripartum change in hematocrit | difference between the most recent Ht within one week before delivery and at day 2 postpartum | day 2 | 
| heart rate | bpm | 15, 30, 45, 60 and 120 minutes after delivery | 
| diastolic blood pressure | mmHg | 15, 30, 45, 60 and 120 minutes after delivery | 
| systolic blood pressure | mmHg | 15, 30, 45, 60 and 120 minutes after delivery | 
| number of participants with nausea reported by caregivers |  | 6 hours | 
| number of participants with vomiting reported by caregivers |  | 6 hours | 
| number of participants with phosphenes reported by caregivers |  | 6 hours | 
| number of participants with dizziness reported by caregivers |  | 6 hours | 
| creatinemia | micromol/L | day 2 | 
| urea | g/L | day 2 | 
| prothrombin time (PT) |  | day 2 | 
| aspartate transaminase | IU/L | day 2 | 
| alanine transaminase | IU/L | day 2 | 
| total bilirubin | micromol/L | day 2 | 
| total fibrinogen | g/L | day 2 | 
| number of participants with deep venous thrombosis confirmed by paraclinical exams |  | within twelve weeks after the delivery | 
| number of participants with pulmonary embolism confirmed by paraclinical exams |  | within twelve weeks after the delivery | 
| number of participants with myocardial infarction confirmed by paraclinical exams |  | within twelve weeks after the delivery | 
| number of participants with any thrombotic event confirmed by paraclinical exams |  | within twelve weeks after the delivery | 
| seizure |  | within twelve weeks after the delivery | 
| renal failure | defined by the need for dialysis | within twelve weeks after the delivery | 
| women's satisfaction | assessed by a self-administered questionnaire | day 2 and weeks 8 postpartum | 
| Provider-assessed clinically significant PPH |  | day 2 | 
| Hb drop > 2g/DL |  | day 2 | 
| Active prothrombin time (aPTT) |  | day 2 | 
| aspartate transaminase > 2N |  | day 2 | 
| alanine transaminase > 2N (day 2) |  | day 2 | 
| gravimetrically estimated blood loss > 500mL |  | day 2 | 
| gravimetrically estimated blood loss > 1000 mL |  | day 2 | 
| Shock |  | day 2 | 
| Transfer to Intensive Care Unit |  | twelve weeks after delivery | 
| Death from any cause |  | 42 days postpartum | 
| supplementary uterotonic treatment | proportion of women requiring supplementary uterotonic treatment | day 2 | 
| iron sucrose perfusion | incidence of iron sucrose perfusion | discharge from hospital | 
| mean gravimetrically estimated blood loss |  | at the end of the cesarean delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized, double blind placebo controlled trial, prevention, tranexamic acid, postpartum hemorrhage, cesarean