TRAnexamic Acid for Preventing Blood Loss Following a Cesarean Delivery in Women With Placenta pREVIA (TRAAPrevia)

University Hospital of Bordeaux

Status and phase

Enrolling

Phase 3

Conditions

Postpartum Hemorrhage

Treatments

Drug: Tranexamic Acid / Sodium chloride

Study type

Interventional

Funder types

Other

Identifiers

NCT04304625

CHUBX 2018/64

Details and patient eligibility

About

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

Full 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.

Enrollment

1,380 estimated patients

Sex

Female

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

1,380 participants in 2 patient groups, including a placebo group

Tranexamic acid

Experimental group

Description:

After the routine prophylactic IV or IM injection of the uterotonic used in the hospital protocol's -either oxytocin or carbetocin - (as recommended by the 2014 guidelines for prevention and management of postpartum hemorrhage from the CNGOF), 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 after birth, slowly (over 30-60 seconds), once the cord has been clamped

Treatment:

Drug: Tranexamic Acid / Sodium chloride

Placebo

Placebo Comparator group

Description:

Treatment:

Drug: Tranexamic Acid / Sodium chloride