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

Overview

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.

Interventions

• Drug Tranexamic Acid / Sodium chloride
  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 cla

Primary outcome measures

• Incidence of red blood cell transfusion (binary outcome) between delivery of child and discharge from postpartum hospital stay. [Time frame: baseline]

Secondary outcome measures (12)

• gravimetrically estimated blood loss [Time frame: Baseline]
• Occurrence of calculated blood loss > 1000ml. [Time frame: Baseline]
• Occurrence of calculated blood loss > 1500ml. [Time frame: Baseline]
• mean calculated blood loss [Time frame: Baseline]
• linically significant PPH [Time frame: Baseline]
• shock index [Time frame: 15, 30, 45, 60 and 120 minutes after birth]
• supplementary uterotonic treatment [Time frame: Baseline]
• iron sucrose perfusion [Time frame: Baseline]
• red blood cell units transfusion [Time frame: Baseline]
• number of transfusion [Time frame: Baseline]
• arterial embolisation [Time frame: Baseline]
• maternal postpartum transfer [Time frame: Baseline]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

France · 1 center

• CHU Bordeaux — Bordeaux

Publications

• Sentilhes L, Madar H, Ifrah A, Chretien JM, Deneux-Tharaux C; TRAAPREVIA Study Group, the Groupe de Recherche en Obstetrique et Gynecologie (GROG). Study protocol. TRAAPREVIA-TRAnexamic acid for preventing blood loss following a cesarean delivery in women with a placenta pREVIA or low-lying placenta: a multicenter randomized, double blind, placebo controlled trial. BMC Pregnancy Childbirth. 2025 M PMID 40448004
• Larson NJ, Mergoum AM, Dries DJ, Cook A, Blondeau B, Rogers FB. THE ROLE OF TRANEXAMIC ACID IN POSTPARTUM HEMORRHAGE: A NARRATIVE REVIEW. Shock. 2024 Nov 1;62(5):620-627. doi: 10.1097/SHK.0000000000002455. Epub 2024 Aug 20. PMID 39162220

Identifiers

NCT: NCT04304625 · CHUBX 2018/64

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗