Back to resultsTRAnexamic Acid for Preventing Blood Loss Following a Cesarean Delivery in Women With Placenta pREVIA (TRAAPrevia)
Primary Purpose
Postpartum Hemorrhage
Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Tranexamic Acid / Sodium chloride
Sponsored by
About this trial
This is an interventional treatment trial for Postpartum Hemorrhage focused on measuring Postpartum hemorrhage, tranexamix acid, 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, 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
Sites / Locations
- CHU BordeauxRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Tranexamic acid
Placebo
Arm 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
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
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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)
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
Occurrence of calculated blood loss > 1500ml.
calculated blood loss > 1500 ml
mean calculated blood loss
mean calculated blood loss
linically significant PPH
provider-assessed clinically significant PPH
shock index
mean shock index defined by the ratio of heart rate to systolic blood pressure
supplementary uterotonic treatment
supplementary uterotonic treatment
iron sucrose perfusion
iron sucrose perfusion until discharge
red blood cell units transfusion
number of red blood cell units transfused between delivery of child and discharge from postpartum hospital stay.
number of transfusion
proportion of women transfused between delivery of child and 24 hours postpartum
arterial embolisation
arterial embolisation or emergency surgery for PPH
maternal postpartum transfer
maternal postpartum transfer to a higher level of care
change in peripartum Hb
mean change in peripartum Hb (difference between most recent Hb within 7 days before surgery and at day 2 postpartum).
change in peripartum Ht
mean change in peripartum Ht (difference between most recent Ht within 7 days before surgery and at day 2 postpartum).
proportion of breastfeeding at hospital discharge
proportion of breastfeeding at hospital discharge
maternal death for any cause
maternal death for any cause
mild adverse reactions of TXA
mild adverse reactions of TXA for women (e.g.: nausea, vomiting, phosphenes, dizziness)
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)
transfer to neonatal ICU
neonatal outcomes: transfer to neonatal ICU
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).
Full Information
NCT ID
NCT04304625
First Posted
March 9, 2020
Last Updated
April 27, 2023
Sponsor
University Hospital, Bordeaux
1. Study Identification
Unique Protocol Identification Number
NCT04304625
Brief Title
TRAnexamic Acid for Preventing Blood Loss Following a Cesarean Delivery in Women With Placenta pREVIA
Acronym
TRAAPrevia
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
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 7, 2020 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
December 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Bordeaux
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postpartum Hemorrhage
Keywords
Postpartum hemorrhage, tranexamix acid, placenta previa
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Multicenter double-blind randomized controlled trial
Masking
ParticipantInvestigator
Masking Description
Double blinding is performed according to current Good Manufacturing Practices (BPF). The packaging and labelling of the experimental drugs are carried out by the PUI of CHU Angers, in accordance with the regulation of the clinical trials in force. PUI of CHU Angers will produce batches of vials (tranexamic acid or placebo according to randomization) according to the model:
TXA: 1g - 10ml
Placebo: NaCl 0.9% - 10mL
Allocation
Randomized
Enrollment
1380 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Tranexamic acid
Arm Type
Experimental
Arm 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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm 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
Intervention Type
Drug
Intervention Name(s)
Tranexamic Acid / Sodium chloride
Intervention 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
Primary Outcome Measure Information:
Title
Incidence of red blood cell transfusion (binary outcome) between delivery of child and discharge from postpartum hospital stay.
Description
Incidence of red blood cell transfusion (binary outcome) between delivery of child and discharge from postpartum hospital stay.
Time Frame
baseline
Secondary Outcome Measure Information:
Title
gravimetrically estimated blood loss
Description
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)
Time Frame
Baseline
Title
Occurrence of calculated blood loss > 1000ml.
Description
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
Time Frame
Baseline
Title
Occurrence of calculated blood loss > 1500ml.
Description
calculated blood loss > 1500 ml
Time Frame
Baseline
Title
mean calculated blood loss
Description
mean calculated blood loss
Time Frame
Baseline
Title
linically significant PPH
Description
provider-assessed clinically significant PPH
Time Frame
Baseline
Title
shock index
Description
mean shock index defined by the ratio of heart rate to systolic blood pressure
Time Frame
15, 30, 45, 60 and 120 minutes after birth
Title
supplementary uterotonic treatment
Description
supplementary uterotonic treatment
Time Frame
Baseline
Title
iron sucrose perfusion
Description
iron sucrose perfusion until discharge
Time Frame
Baseline
Title
red blood cell units transfusion
Description
number of red blood cell units transfused between delivery of child and discharge from postpartum hospital stay.
Time Frame
Baseline
Title
number of transfusion
Description
proportion of women transfused between delivery of child and 24 hours postpartum
Time Frame
Baseline
Title
arterial embolisation
Description
arterial embolisation or emergency surgery for PPH
Time Frame
Baseline
Title
maternal postpartum transfer
Description
maternal postpartum transfer to a higher level of care
Time Frame
Baseline
Title
change in peripartum Hb
Description
mean change in peripartum Hb (difference between most recent Hb within 7 days before surgery and at day 2 postpartum).
Time Frame
day 2
Title
change in peripartum Ht
Description
mean change in peripartum Ht (difference between most recent Ht within 7 days before surgery and at day 2 postpartum).
Time Frame
day 2
Title
proportion of breastfeeding at hospital discharge
Description
proportion of breastfeeding at hospital discharge
Time Frame
Baseline
Title
maternal death for any cause
Description
maternal death for any cause
Time Frame
Baseline
Title
mild adverse reactions of TXA
Description
mild adverse reactions of TXA for women (e.g.: nausea, vomiting, phosphenes, dizziness)
Time Frame
Hospitalization stay
Title
thromboembolic events
Description
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)
Time Frame
week 12
Title
transfer to neonatal ICU
Description
neonatal outcomes: transfer to neonatal ICU
Time Frame
Baseline
Title
Women's satisfaction and psychological status
Description
Women's satisfaction and psychological status (self-administered questionnaire at day 2 postpartum and self-administered questionnaire sent by mail at 8 weeks).
Time Frame
Week 8; Week 12
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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, 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Loic Sentilhes, MD, PhD
Phone
+335 56 79 55 79
Email
loic.sentilhes@chu-bordeaux.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Aurélie Darmaillacq
Email
aurelie.darmaillacq@chu-bordeaux.fr
Facility Information:
Facility Name
CHU Bordeaux
City
Bordeaux
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Loic Sentilhes Sentilhes, MD, PhD
Email
loic.sentilhes@chu-bordeaux.fr
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
TRAnexamic Acid for Preventing Blood Loss Following a Cesarean Delivery in Women With Placenta pREVIA
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