Clinical trial NCT04304625: TRAnexamic Acid for Preventing Blood Loss Following a Cesarean Delivery in Women With Placenta pREVIA
Official title: TRAnexamic Acid for Preventing Blood Loss Following a Cesarean Delivery in Women With Placenta pREVIA: a Multicenter Randomised, Double Blind Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Postpartum Hemorrhage
Keywords: Postpartum hemorrhage
tranexamix acid
placenta previa
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2020-03-11
Enrollment: 1380
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter double-blind randomized controlled trial
Primary purpose: TREATMENT

Brief summary: Several randomized, controlled trials, mostly involving women undergoing cesarean delivery, have shown that the prophylactic intravenous administration of 1 g of tranexamic acid after childbirth reduced blood loss. Most were small, single-centre trials with considerable methodologic limitations.

It is important to emphasize that none of these RCTs has included women at increased risk of PPH such as placenta previa, a context in which the prevalence of moderate and severe blood loss is significantly higher and where the magnitude of the effect of TXA may highly differ compared to low risk women

Detailed description: TXA is a promising candidate drug, inexpensive and easy to administer, that can be easily added to the delivery management of women worldwide. Strong evidence that TXA reduces blood transfusion in elective and emergency surgery, outside obstetrics, has been available for many years, whatever the type of surgery (ie cardiac, orthopaedic, hepatic, urological, and vascular surgery). Tranexamic acid was recently shown to reduce bleeding-related mortality among women with postpartum hemorrhage, especially when the drug was administered shortly after delivery. A meta-analysis of data from individual patients including data from patients with trauma and women with postpartum hemorrhage suggested the importance of early treatment.

Several randomized, controlled trials (RCTs), involving women undergoing cesarean delivery, as well have meta-analyses, have shown that the prophylactic intravenous administration of 1 g of tranexamic acid after childbirth reduced blood loss. Most of them were small, single- center trials with considerable methodologic limitations. Thus, no guidelines advocate the use of tranexamic acid to prevent blood loss after cesarean delivery. Moreover, it is important to emphasize that none of these RCTs has included women at increased risk of PPH such as placenta previa, a context in which the prevalence of moderate and severe blood loss is significantly higher and where the magnitude of the effect of TXA may highly differ compared to low risk women.

The aim of our study is to conduct a large multicentre randomised, double blind placebo controlled trial to adequately assess the impact of TXA for preventing PPH following a cesarean delivery in women with placenta previa.

Eligibility criteria: Inclusion Criteria:

* Age≥ 18 years
* Placenta previa defined by a placental edge below 20mm from internal cervical os diagnosed at the most recent transvaginal ultrasound examination before delivery, as per French guidelines
* Cesarean delivery before or during labor
* Gestational age at delivery ≥ 32 weeks + 0
* Affiliated or beneficiary to a health security system
* Signed informed consent

Exclusion Criteria:

* History of venous (deep vein thrombosis and/or pulmonary embolism) or arterial (angina pectoris, myocardial infarction, stroke) thrombotic event
* History of epilepsy or seizure
* Chronic or acute cardiovascular disease (including foramen oval, mitral stenosis, aortic stenosis, heart transplant, pulmonary hypertension); chronic or acute renal disease (including chronic or acute kidney failure with glomerular filtration rate \<90 mL/min, renal transplantation), chronic active or acute liver disorder with hemorrhagic or thrombotic risk (including cirrhosis, portal hypertension, Budd-Chiari syndrome)
* Active autoimmune disease with thromboembolic risk (including lupus, antiphospholipid syndrome, Crohn's disease)
* Sickle cell disease (homozygous)
* Severe hemostasis disorder prothrombotic (Factor V Leiden mutation - homo or heterozygous; Activated protein C (APC) resistance, Protein C deficiency, Protein S deficiency - aside from pregnancy, Homocysteinemia, , Factor 2 mutation - homo or heterozygous, Deficiency in antithrombin 3), prohemorragic (von Willebrand disease requiring desmopressin treatment during delivery, thrombocytopenia (\<30000/mm3), Glanzmann disease, hypofibrinogenemia (\<1g/L) -aside from pregnancy)
* High prenatal suspicion of placenta accreta spectrum disorder according to the obstetrician in charge
* Placenta praevia diagnosed during delivery
* Abruptio placentae
* Significant bleeding (estimated blood loss\>500ml) within 12 hours before cesarean delivery
* Eclampsia / HELLP syndrome
* In utero fetal death
* Administration of low-molecular-weight heparin or antiplatelet agents during the 7 days before delivery
* Tranexamic acid contraindication
* Sodium chloride contraindication
* Women under legal protection
* Poor understanding of the French language

Primary outcomes:
measure: Incidence of red blood cell transfusion (binary outcome) between delivery of child and discharge from postpartum hospital stay.
timeFrame: baseline
Secondary outcomes:
measure: gravimetrically estimated blood loss
timeFrame: Baseline
measure: Occurrence of calculated blood loss > 1000ml.
timeFrame: Baseline
measure: Occurrence of calculated blood loss > 1500ml.
timeFrame: Baseline
measure: mean calculated blood loss
timeFrame: Baseline
measure: linically significant PPH
timeFrame: Baseline
measure: shock index
timeFrame: 15, 30, 45, 60 and 120 minutes after birth
measure: supplementary uterotonic treatment
timeFrame: Baseline
measure: iron sucrose perfusion
timeFrame: Baseline
measure: red blood cell units transfusion
timeFrame: Baseline
measure: number of transfusion
timeFrame: Baseline
measure: arterial embolisation
timeFrame: Baseline
measure: maternal postpartum transfer
timeFrame: Baseline
measure: change in peripartum Hb
timeFrame: day 2
measure: change in peripartum Ht
timeFrame: day 2
measure: proportion of breastfeeding at hospital discharge
timeFrame: Baseline
measure: maternal death for any cause
timeFrame: Baseline
measure: mild adverse reactions of TXA
timeFrame: Hospitalization stay
measure: thromboembolic events
timeFrame: week 12
measure: transfer to neonatal ICU
timeFrame: Baseline
measure: Women's satisfaction and psychological status
timeFrame: Week 8; Week 12
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU Bordeaux
Study officials:
References: