TRAnexamic Acid for Preventing blood loss following a cesarean delivery in women with placenta pREVIA: a multicenter randomised, double blind placebo controlled trial. TRAAPrevia

2024-515276-12-00 Protocol CHUBX 2018/64 Therapeutic confirmatory (Phase III) Ongoing, recruiting

Start 1 Jul 2020 · Status Ongoing, recruiting · 1 EU/EEA countries · 32 sites · Protocol CHUBX 2018/64

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruiting
Participants planned 1,380
Countries 1
Sites 32

Postpartum Hemorrhage

To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on the incidence of red blood cell (RBC) transfusion between delivery of child and discharge from postpart…

Key facts

Sponsor
Centre Hospitalier Universitaire De Bordeaux
Participant type
Patients
Age range
18-64 years
Gender
Female
Therapeutic area
Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]
Trial duration
1 Jul 2020 → ongoing
Decision date (initial)
2024-09-17
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
French Ministry of Social Affairs and Health

External identifiers

EU CT number
2024-515276-12-00
EudraCT number
2019-004439-22
ClinicalTrials.gov
NCT04304625

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Prophylaxis, Therapy, Efficacy

To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on the incidence of red blood cell (RBC) transfusion between delivery of child and discharge from postpartum hospital stay

Secondary objectives 19

  1. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on mean gravimetrically estimated blood loss by measuring the suction volume and swab weight
  2. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on incidence of calculated blood loss > 1000ml
  3. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on incidence of calculated blood loss > 1500 ml
  4. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on mean calculated blood loss
  5. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on incidence of provider-assessed clinically significant PPH
  6. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on mean shock index measured at 15, 30, 45, 60 and 120 minutes after birth, or if PPH occurs
  7. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on proportion of women requiring supplementary uterotonic treatment
  8. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on proportion of women receiving iron sucrose perfusion until discharge
  9. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on mean number of red blood cell units transfused between delivery of child and discharge from postpartum hospital stay
  10. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on proportion of women transfused between delivery of child and 24 hours postpartum
  11. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on proportion of women requiring arterial embolisation or emergency surgery for PPH
  12. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on incidence of maternal postpartum transfer to a higher level of care
  13. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on mean change in peripartum Hb and Ht (difference between most recent Hb and Ht within the 7 days before cesarean and at day 2 postpartum).
  14. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on proportion of breastfeeding at hospital discharge
  15. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on maternal death for any cause
  16. To compare the occurrence of nausea, vomiting, phosphenes, dizziness (identified in the theatre room as well as during the postpartum stay in hospital) of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery versus placebo
  17. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on the occurrence of maternal thromboembolic events and other severe unexpected adverse reactions (i.e. incidence de deep vein thrombosis, pulmonary embolism, myocardial infarction, seizure, renal failure necessitating dialysis ) - (these events will be assessed up to twelve weeks after the delivery, telephone interview at 12 weeks postpartum);
  18. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on the occurrence of neonatal adverse outcomes: transfer to neonatal ICU, hospitalisation within 12 weeks after birth
  19. To compare the effect of a low dose of TXA (1g) administered within 3 minutes after delivery of the child in addition to prophylactic uterotonic in women with placenta previa and cesarean delivery, versus placebo, on women’s satisfaction and psychological status: these will be assessed by a self-administered questionnaire at day 2 postpartum [77, 118, 135, 148] and by a self-administered questionnaire sent by mail at 8 weeks.

Conditions and MedDRA coding

Postpartum Hemorrhage

VersionLevelCodeTermSystem organ class
20.0 LLT 10074685 Placenta previa 10036585
20.1 LLT 10019580 Hemorrhage postpartum 10036585

Study design 2 periods

#TitleAllocationBlindingRoles blindedArms
1 Experimental period
After the routine prophylactic IV or IM injection of the uterotonic used in the hospital protocol’s -either oxytocin or carbetocin, 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
 Randomised Controlled Double [{"id":80966,"code":2,"name":"Investigator"},{"id":80969,"code":5,"name":"Carer"},{"id":80967,"code":1,"name":"Subject"},{"id":80968,"code":3,"name":"Monitor"}] Tranexamic acid: intravenous administration of 10-mL of tranexamic acid (EXACYL® 1 g/10 ml I.V., solution injectable)
Placebo: sodium intravenous administration of 10-mL of chloride solution (0.9% -10mL).
2 Following period
Women are followed for 12 weeks post-partum with questionnaires to be completed at 8 and 12 xeeks post-partum.
 Randomised Controlled Double [{"id":80972,"code":3,"name":"Monitor"},{"id":80971,"code":5,"name":"Carer"},{"id":80973,"code":2,"name":"Investigator"},{"id":80974,"code":1,"name":"Subject"}] Tranexamic acid: intravenous administration of 10-mL of tranexamic acid (EXACYL® 1 g/10 ml I.V., solution injectable)
Placebo: sodium intravenous administration of 10-mL of chloride solution (0.9% -10mL)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. Age≥ 18 years
  2. 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
  3. Cesarean delivery before or during labor
  4. Gestational age at delivery ≥ 32 weeks + 0
  5. Affiliated or beneficiary to a health security system
  6. Signed informed consent

Exclusion criteria 19

  1. History of venous (deep vein thrombosis and/or pulmonary embolism) or arterial (angina pectoris, myocardial infarction, stroke) thrombotic event
  2. History of epilepsy or seizure
  3. Chronic or acute cardiovascular disease (including foramen oval, mitral stenosis, aortic stenosis, heart transplant, pulmonary hypertension)
  4. Chronic or acute renal disease (including chronic or acute kidney failure with glomerular filtration rate <90 mL/min, renal transplantation)
  5. Chronic active, or acute, liver disorder with hemorrhagic or thrombotic risk (including cirrhosis, portal hypertension, Budd-Chiari syndrome)
  6. Active autoimmune disease with thromboembolic risk (including lupus, antiphospholipid syndrome, Crohn’s disease)
  7. Sickle cell disease (homozygous)
  8. 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 such as von Willebrand disease requiring desmopressin treatment during delivery, Thrombocytopenia (< 30 000 /mm3), Glanzmann disease, hypofibrinogenemia (< 1 g/L) aside from pregnancy)
  9. High prenatal suspicion of placenta accreta spectrum disorder according to the obstetrician in charge
  10. Placenta praevia diagnosed during delivery
  11. Abruptio placentae
  12. Significant bleeding (estimated blood loss > 500ml) within 12 hours before cesarean delivery
  13. Eclampsia / HELLP syndrome
  14. In utero fetal death
  15. Administration of low-molecular-weight heparin or antiplatelet agents during the 7 days before delivery
  16. Tranexamic acid contraindication
  17. Sodium chloride contraindication
  18. Women under legal protection
  19. Poor understanding of the French language

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Incidence of red blood cell transfusion between delivery of child and discharge from postpartum hospital stay.

Secondary endpoints 20

  1. Mean gravimetrically estimated blood loss, by measuring the suction volume and swab weight according to Gai et al (estimated blood loss = (weight of materials used + materials not used - weight of all materials before surgery)/1.05 + volume included in the suction container)
  2. Calculated blood loss > 1000 mL. Calculated blood loss = estimated blood volume × (preoperative Ht -postoperative Ht)/preoperative Ht (where estimated blood volume = weight (kg) × 85) [32, 135]. Preoperative Ht will be the most recent Ht within one week before delivery. Postoperative Ht will be measured at day 2 postpartum,
  3. Calculated blood loss > 1500 ml
  4. Mean calculated blood loss
  5. Mean shock index, defined by the ratio of heart rate to systolic blood pressure, measured at 15, 30, 45, 60 and 120 minutes after birth, or if PPH occurs
  6. Supplementary uterotonic treatment
  7. Iron sucrose perfusion until discharge
  8. Number of red blood cell units transfused between delivery of child and discharge from postpartum hospital stay.
  9. Proportion of women transfused between delivery of child and 24 hours postpartum
  10. Arterial embolisation or emergency surgery for PPH
  11. Maternal postpartum transfer to a higher level of care
  12. Proportion of breastfeeding at hospital discharge
  13. Maternal death for any cause
  14. Mean change in peripartum hemoglobin (difference between the most recent Hb within 7 days before delivery and at day 2 postpartum)
  15. Mean change in peripartum hematocrit (difference between the most recent Ht within 7 days before delivery and at day 2 postpartum).
  16. Occurrence of potential mild adverse reactions of TXA for women : nausea, vomiting, phosphenes, dizziness (these events will be identified in the theatre room as well as during the postpartum stay in hospital);
  17. Occurrence of thromboembolic events and other severe unexpected adverse reactions (i.e. incidence of deep vein thrombosis confirmed by radiological exams, pulmonary embolism confirmed by radiological exams, myocardial infarction, seizure, renal failure necessitating dialysis ) - (these events will be assessed up to 12 weeks after the delivery, telephone interview at 12 weeks postpartum)
  18. Occurrence of neonatal outcomes: transfer to neonatal ICU.
  19. Self-administered questionnaire at day 2 postpartum assessing women’s satisfaction regarding their delivery and their psychological status
  20. Self-administered questionnaire sent by mail at 8 weeks of postpartum, assessing their psychological status

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Tranexamic Acid

SCP1109101 · ATC

Active substance
Tranexamic Acid
Substance synonyms
LB1148, 4-(AMINOMETHYL)CYCLOHEXANE-1-CARBOXYLIC ACID, AMCA, TRANS-AMCHA
Route of administration
SOLUTION FOR INJECTION
Max daily dose
20 ml millilitre(s)
Max total dose
20 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B02AA02 — TRANEXAMIC ACID
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

—

SCP12712712 · ATC

Route of administration
INTRAVENOUS
Max daily dose
10 ml millilitre(s)
Max total dose
10 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B05XA03 — SODIUM CHLORIDE
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Bordeaux

27 Total trials 14 Recruiting 6 Ended
Academic / Non-commercial
Sponsor organisation
Centre Hospitalier Universitaire De Bordeaux
Address
12 Rue Dubernat, Cs 91286 Cs 91286
City
Talence
Postcode
33400
Country
France

Scientific contact point

Organisation
Centre Hospitalier Universitaire De Bordeaux
Contact name
Coordinating investigator

Public contact point

Organisation
Centre Hospitalier Universitaire De Bordeaux
Contact name
Coordinating investigator

Locations

1 EU/EEA country · 32 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ongoing, recruiting 1,380 32
Rest of world — 0 —

Investigational sites

France

32 sites · Ongoing, recruiting
Centre Hospitalier De Pau
Gynécologie, 4 Boulevard Hauterive, 64000, Pau
Centre Hospitalier Universitaire De Toulouse
Gynécologie Obstétrique, 330 Avenue De Grande Bretagne, 31059, Toulouse Cedex 9
Centre Hospitalier Universitaire De Poitiers
Maternité, 2 Rue De La Miletrie, 86000, Poitiers
Assistance Publique Hopitaux De Paris
Gynécologie Obstétrique, 27 Rue Du Faubourg Saint Jacques, 75014, Paris
Centre Hospitalier Universitaire De Rennes
Gynécologie Obstétrique, 2 Rue Henri Le Guilloux, 35000, Rennes
Les Hopitaux Universitaires De Strasbourg
Gynécologie Obstétrique, 1 Avenue Moliere, Bp 49, Strasbourg Cedex 2
Assistance Publique Hopitaux De Paris
Maternité, 149 Rue De Sevres, 75015, Paris
Centre Hospitalier Intercommunal De Poissy Saint Germain
Gynécologie Obstétrique, Residence Les Maisonnees, 10 Rue Du Champ Gaillard, Poissy
CHRU De Nancy
Gynécologie Obstétrique, 29 Avenue Du Mal De Lattre De Tassigny, 54000, Nancy
Centre Hospitalier Intercommunal Creteil
Maternité, 40 Avenue De Verdun, 94000, Creteil
Centre Hospitalier Regional Universitaire De Tours
Gynécologie Obstétrique, 2 Boulevard Tonnelle, 37044, Tours Cedex 9
Centre Hospitalier Universitaire De Montpellier
Gynécologie Obstétrique, 191 Avenue Du Doyen Gaston Giraud, 34295, Montpellier Cedex 5
Hospices Civils De Lyon
Gynécologie Obstétrique, 165 Chemin Du Grand Revoyet, 69310, Pierre Benite
Assistance Publique Hopitaux De Paris
Gynécologie Obstétrique, 157 Rue De La Porte De Trivaux, 92140, Clamart
Assistance Publique Hopitaux De Paris
Gynécologie Obstétrique, 26 Avenue Du Docteur Arnold Netter, 75012, Paris
Centre Hospitalier Universitaire De Saint Etienne
Gynécologie Obstétrique, Avenue Albert Raimond, 42270, Saint Priest En Jarez
University Hospital Of Clermont-Ferrand
Pôle Mère-Enfant, 1 Place Lucie Et Raymond Aubrac, 63100, Clermont-Ferrand
Centre Hospitalier Universitaire De Bordeaux
Gynécologie Obstétrique, Place Amelie Raba Leon, 33000, Bordeaux
Centre Hospitalier Universitaire De Nantes
Gynécologie Obstétrique, 38 Boulevard Jean Monnet, 44000, Nantes
Assistance Publique Hopitaux De Paris
Gynécologie Obstétrique, 78 Rue Du General Leclerc, 94270, Le Kremlin-Bicetre
Hopital Saint Joseph
Gynécologie -Obstétrique, Pôle Parents-Enfants, 26 Boulevard De Louvain, 13008, Marseille
Centre Hospitalier Universitaire De Lille
Gynécologie Obstétrique, Avenue Eugene Avinee, 59037, Lille Cedex
CHU Besancon
Pôle Mère-Enfant, 3 Boulevard Alexander Fleming, Cs 81816, Besancon Cedex
Centre Hospitalier Universitaire D'Angers
Gynécologie Obstétrique, 4 Rue Larrey, 49100, Angers
Centre Hospitalier Universitaire De Dijon
Gynécologie-Obstétrique et Biologie de la reproduction, 14 Rue Paul Gaffarel, 21000, Dijon
Centre Hospitalier Universitaire De Nimes
Gynécologie Obstétrique, 4 Place Du Professeur Robert Debre, Bp 40026, Nimes Cedex 9
Centre Hospitalier Regional De Marseille
Gynécologie Obstétrique, 265 Chemin Des Bourrely, 13015, Marseille
Centre Hospitalier General De St Denis
Maternité, 2 Rue Du Docteur Delafontaine, Bp 279, St Denis Cedex
GIE Groupe hospitalier Paris Saint-Joseph/Vinci
Gynécologie Obstétrique, 185 Rue Raymond Losserand, 75674, Paris Cedex 14
Centre Hospitalier Universitaire Rouen
Gynécologie Obstétrique, 1 Rue De Germont, Bp 96031, Rouen Cedex
Centre Hospitalier Regional De Marseille
Gynécologie Obstétrique, 147 Boulevard Baille, 13005, Marseille
Assistance Publique Hopitaux De Paris
Gynécologie Obstétrique, 48 Boulevard Serurier, 75019, Paris

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2020-07-01 2020-08-07

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_2024-515276-12-00_public 5.0
Recruitment arrangements (for publication) Document not required 1
Subject information and informed consent form (for publication) L1_SIS and ICF adults_2024-515273-12-00 2.0
Summary of Product Characteristics (SmPC) (for publication) TRAAPrevia_RCP Exacyl_06 08 2018 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_2024-515276-12-00 Public 5.0

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-08-23 France Acceptable
2024-09-17
 2024-09-17