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

TRAnexamic Acid for Preventing Blood Loss Following a Cesarean Delivery in Women With Placenta pREVIA: a Multicenter Randomised, Double Blind Placebo Controlled Trial

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

Study Overview

• Status: Recruiting
• Conditions: Postpartum Hemorrhage
• Intervention / Treatment: Drug: Tranexamic Acid / Sodium chloride

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.

• Study Type: Interventional
• Enrollment (Estimated): 1380
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Loic Sentilhes, MD, PhD; Phone Number: +335 56 79 55 79; Email: loic.sentilhes@chu-bordeaux.fr
• Study Contact Backup: Name: Aurélie Darmaillacq; Email: aurelie.darmaillacq@chu-bordeaux.fr

Study Locations

• France
  • Bordeaux, France
    • Recruiting
    • CHU Bordeaux
    • Contact: Loic Sentilhes Sentilhes, MD, PhD; Email: loic.sentilhes@chu-bordeaux.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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, ASAT>3N, 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tranexamic acid; 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	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 clamped
Placebo Comparator: Placebo; 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	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 clamped

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of red blood cell transfusion (binary outcome) between delivery of child and discharge from postpartum hospital stay.	Incidence of red blood cell transfusion (binary outcome) between delivery of child and discharge from postpartum hospital stay.	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gravimetrically estimated blood loss	gravimetrically estimated blood loss by measuring the suction volume and swab weight (estimated blood loss = (weight of materials used + materials not used - weight of all materials before surgery)/1.05 + volume included in the suction container)	Baseline
Occurrence of calculated blood loss > 1000ml.	Calculated blood loss = estimated blood volume × (preoperative Ht - postoperative Ht)/preoperative Ht (where estimated blood volume = weight (kg) × 85). Preoperative Ht will be the most recent Ht within 7 days before delivery. Postoperative Ht will be measured at day 2 postpartum	Baseline
Occurrence of calculated blood loss > 1500ml.	calculated blood loss > 1500 ml	Baseline
mean calculated blood loss	mean calculated blood loss	Baseline
linically significant PPH	provider-assessed clinically significant PPH	Baseline
shock index	mean shock index defined by the ratio of heart rate to systolic blood pressure	15, 30, 45, 60 and 120 minutes after birth
supplementary uterotonic treatment	supplementary uterotonic treatment	Baseline
iron sucrose perfusion	iron sucrose perfusion until discharge	Baseline
red blood cell units transfusion	number of red blood cell units transfused between delivery of child and discharge from postpartum hospital stay.	Baseline
number of transfusion	proportion of women transfused between delivery of child and 24 hours postpartum	Baseline
arterial embolisation	arterial embolisation or emergency surgery for PPH	Baseline
maternal postpartum transfer	maternal postpartum transfer to a higher level of care	Baseline
change in peripartum Hb	mean change in peripartum Hb (difference between most recent Hb within 7 days before surgery and at day 2 postpartum).	day 2
change in peripartum Ht	mean change in peripartum Ht (difference between most recent Ht within 7 days before surgery and at day 2 postpartum).	day 2
proportion of breastfeeding at hospital discharge	proportion of breastfeeding at hospital discharge	Baseline
maternal death for any cause	maternal death for any cause	Baseline
mild adverse reactions of TXA	mild adverse reactions of TXA for women (e.g.: nausea, vomiting, phosphenes, dizziness)	Hospitalization stay
thromboembolic events	Occurrence of thromboembolic events and other severe unexpected adverse reactions (e.g incidence of deep vein thrombosis confirmed by radiological exams, pulmonary embolism confirmed by radiological exams, myocardial infarction, seizure, renal failure necessitating dialysis)	week 12
transfer to neonatal ICU	neonatal outcomes: transfer to neonatal ICU	Baseline
Women's satisfaction and psychological status	Women's satisfaction and psychological status (self-administered questionnaire at day 2 postpartum and self-administered questionnaire sent by mail at 8 weeks).	Week 8; Week 12

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2020
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: March 9, 2020
• First Submitted That Met QC Criteria: March 9, 2020
• First Posted (Actual): March 11, 2020

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Postpartum hemorrhage; placenta previa; tranexamix acid
• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Placenta Diseases; Puerperal Disorders; Uterine Hemorrhage; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hemorrhage; Postpartum Hemorrhage; Placenta Previa; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: CHUBX 2018/64

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No