Clinical trial NCT03431805: TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery
Official title: TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery :a Multicenter Randomised, Double Blind Placebo Controlled Trial (TRAAP2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postpartum Hemorrhage
Keywords: Randomized
double blind placebo controlled trial
prevention
tranexamic acid
postpartum hemorrhage
cesarean
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2018-02-13
Enrollment: 4574
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim is to assess the impact of tranexamic acid (TXA) for preventing postpartum hemorrhage (PPH) following a cesarean section (CS).

Detailed description: Regarding the prevention of PPH, recent randomized controlled trials (RCTs) of unclear quality have suggested that TXA may reduce blood loss and maternal morbidity, while a Cochrane Collaboration review has concluded, that "TXA (in addition to uterotonic medications) decreases postpartum blood loss and prevents PPH and blood transfusions following vaginal birth and CS in women at low risk of PPH based on studies of mixed quality. Further investigations are needed on efficacy and safety of this regimen for preventing PPH.

Treatment, that is a 10-mL blinded vial of the study drug (either 1g TXA or placebo according to the randomization sequence), will be administered intravenously to the participant women during the third stage of labor of cesarean delivery.

The follow-up visit will take place in the postpartum ward of the maternity unit, on D2 postpartum. This stage will include a venous blood sample to measure plasma concentrations of Hb and Ht, urea and creatinemia, prothrombin time (PT), active prothrombin time (aPTT), aspartate and alanine transaminase, total bilirubin and fibrinogen, and the completion of a self-questionnaire about satisfaction by the women, as well as the assessment of the adverse events.

At 8 weeks postpartum, a self-questionnaire assessing psychological status and well-being will be sent to the women. At 12 weeks postpartum, all participants will be contacted by phone to assess the incidence of thrombotic and any other significant events.

Eligibility criteria: Inclusion Criteria:

* : adult women admitted for a cesarean delivery before or during labor, at a term ≥ 34 weeks,
* hemoglobin level at the last blood sample \>9g/dl,
* available blood test for Hb and Ht within one week before caesarean delivery,
* informed signed consent

Exclusion Criteria:

* previous thrombotic event or preexisting pro-thrombotic disease,
* epileptic state or history of seizures,
* presence of any chronic or active cardiovascular disease outside hypertension,
* any chronic or active renal disease and chronic or active liver disease at risk thrombotic or hemorrhagic, autoimmune disease,
* sickle cell disease,
* placenta praevia,
* placenta accreta/increta/percreta,
* abruption placentae,
* eclampsia,
* HELLP syndrome,
* significant hemorrhage before cesarean section
* in utero fetal death,
* administration of low-molecular-weight heparin or antiplatelet agents during the week before delivery,
* planned general anesthesia,
* hypersensitivity to tranexamic acid or concentrated hydrochloric acid,
* instrumental extraction failure,
* multiple pregnancy with vaginal delivery of the first child,
* poor understanding of the French language.

Primary outcomes:
measure: postpartum hemorrhage
timeFrame: day 2
Secondary outcomes:
measure: mean calculated blood loss > 500mL
timeFrame: day 2
measure: mean calculated blood loss > 1500mL
timeFrame: day 2
measure: total mean calculated blood loss
timeFrame: day 2
measure: mean gravimetrically estimated blood loss
timeFrame: 6 hours
measure: incidence of postpartum transfusion
timeFrame: day 2
measure: Mean or median number of units of red blood cells transfused
timeFrame: day 2
measure: incidence of arterial embolisation or emergency surgery for PPH
timeFrame: 3 months
measure: mean peripartum change in haemoglobin
timeFrame: day 2
measure: mean peripartum change in hematocrit
timeFrame: day 2
measure: heart rate
timeFrame: 15, 30, 45, 60 and 120 minutes after delivery
measure: diastolic blood pressure
timeFrame: 15, 30, 45, 60 and 120 minutes after delivery
measure: systolic blood pressure
timeFrame: 15, 30, 45, 60 and 120 minutes after delivery
measure: number of participants with nausea reported by caregivers
timeFrame: 6 hours
measure: number of participants with vomiting reported by caregivers
timeFrame: 6 hours
measure: number of participants with phosphenes reported by caregivers
timeFrame: 6 hours
measure: number of participants with dizziness reported by caregivers
timeFrame: 6 hours
measure: creatinemia
timeFrame: day 2
measure: urea
timeFrame: day 2
measure: prothrombin time (PT)
timeFrame: day 2
measure: aspartate transaminase
timeFrame: day 2
measure: alanine transaminase
timeFrame: day 2
measure: total bilirubin
timeFrame: day 2
measure: total fibrinogen
timeFrame: day 2
measure: number of participants with deep venous thrombosis confirmed by paraclinical exams
timeFrame: within twelve weeks after the delivery
measure: number of participants with pulmonary embolism confirmed by paraclinical exams
timeFrame: within twelve weeks after the delivery
measure: number of participants with myocardial infarction confirmed by paraclinical exams
timeFrame: within twelve weeks after the delivery
measure: number of participants with any thrombotic event confirmed by paraclinical exams
timeFrame: within twelve weeks after the delivery
measure: seizure
timeFrame: within twelve weeks after the delivery
measure: renal failure
timeFrame: within twelve weeks after the delivery
measure: women's satisfaction
timeFrame: day 2 and weeks 8 postpartum
measure: Provider-assessed clinically significant PPH
timeFrame: day 2
measure: Hb drop > 2g/DL
timeFrame: day 2
measure: Active prothrombin time (aPTT)
timeFrame: day 2
measure: aspartate transaminase > 2N
timeFrame: day 2
measure: alanine transaminase > 2N (day 2)
timeFrame: day 2
measure: gravimetrically estimated blood loss > 500mL
timeFrame: day 2
measure: gravimetrically estimated blood loss > 1000 mL
timeFrame: day 2
measure: Shock
timeFrame: day 2
measure: Transfer to Intensive Care Unit
timeFrame: twelve weeks after delivery
measure: Death from any cause
timeFrame: 42 days postpartum
measure: supplementary uterotonic treatment
timeFrame: day 2
measure: iron sucrose perfusion
timeFrame: discharge from hospital
measure: mean gravimetrically estimated blood loss
timeFrame: at the end of the cesarean delivery
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Besançon
country: France
facility: CHU Jean Minjoz
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Caen
country: France
facility: CHRU Côte de Nacre
city: Clermont Ferrand
country: France
facility: CHU Estain
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Créteil
city: Marseille
country: France
facility: Hôpital Saint Joseph Marseille
city: Marseille
country: France
facility: Hopital Nord
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nancy
country: France
facility: CHRU de Nancy
city: Nantes
country: France
facility: CHU Nantes
city: Nîmes
country: France
facility: CHU Nîmes
city: Paris
country: France
facility: Hôpital Trousseau
city: Paris
country: France
facility: Hôpital Saint Joseph Paris
city: Paris
country: France
facility: Maternité de Port-Royal Paris
city: Paris
country: France
facility: Hôpital universitaire Necker-Enfants malades
city: Paris
country: France
facility: Hôpital universitaire Robert Debré
city: Paris
country: France
facility: Hôpital universitaire Kremlin-Bicètre
city: Pau
country: France
facility: CH de Pau
city: Poissy
country: France
facility: Centre Hospitalier Intercommunal Poissy-Saint Germain
city: Rennes
country: France
facility: CHU Rennes
city: Rouen
country: France
facility: CHU Charles Nicolle
city: Saint Etienne
country: France
facility: CHU Saint Etienne
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Toulouse
country: France
facility: Hôpital Paule de Viguier CHU Toulouse
city: Tours
country: France
facility: CHU Tours
Study officials:
References:
citation: Sentilhes L, Senat MV, Le Lous M, Winer N, Rozenberg P, Kayem G, Verspyck E, Fuchs F, Azria E, Gallot D, Korb D, Desbriere R, Le Ray C, Chauleur C, de Marcillac F, Perrotin F, Parant O, Salomon LJ, Gauchotte E, Bretelle F, Sananes N, Bohec C, Mottet N, Legendre G, Letouzey V, Haddad B, Vardon D, Madar H, Mattuizzi A, Daniel V, Regueme S, Roussillon C, Benard A, Georget A, Darsonval A, Deneux-Tharaux C; Groupe de Recherche en Obstetrique et Gynecologie. Tranexamic Acid for the Prevention of Blood Loss after Cesarean Delivery. N Engl J Med. 2021 Apr 29;384(17):1623-1634. doi: 10.1056/NEJMoa2028788.
citation: Sentilhes L, Daniel V, Deneux-Tharaux C; TRAAP2 Study Group and the Groupe de Recherche en Obstetrique et Gynecologie (GROG). TRAAP2 - TRAnexamic Acid for Preventing postpartum hemorrhage after cesarean delivery: a multicenter randomized, doubleblind, placebo- controlled trial - a study protocol. BMC Pregnancy Childbirth. 2020 Jan 31;20(1):63. doi: 10.1186/s12884-019-2718-4.