TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery (TRAAP2)

TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery :a Multicenter Randomised, Double Blind Placebo Controlled Trial (TRAAP2)

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

Study Overview

• Status: Completed
• Conditions: Postpartum Hemorrhage
• Intervention / Treatment: Drug: Tranexamic Acid Injectable Solution; Drug: Sodium Chloride 0.9%

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.

• Study Type: Interventional
• Enrollment (Actual): 4574
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France, 49033
    • CHU Angers
  • Besançon, France, 25000
    • CHU Jean Minjoz
  • Bordeaux, France, 33076
    • CHU Bordeaux
  • Caen, France, 14033
    • CHRU Côte de Nacre
  • Clermont Ferrand, France, 63001
    • CHU Estain
  • Créteil, France
    • Centre Hospitalier Intercommunal de Créteil
  • Marseille, France, 13008
    • Hôpital Saint Joseph Marseille
  • Marseille, France, 13915
    • Hopital Nord
  • Montpellier, France, 34295
    • CHU de Montpellier
  • Nancy, France, 54000
    • CHRU de Nancy
  • Nantes, France, 44093
    • CHU Nantes
  • Nîmes, France, 30900
    • CHU Nîmes
  • Paris, France, 75012
    • Hôpital Trousseau
  • Paris, France, 75014
    • Hopital Saint Joseph Paris
  • Paris, France, 75014
    • Maternité de Port-Royal Paris
  • Paris, France, 75015
    • Hopital universitaire Necker-Enfants Malades
  • Paris, France, 75019
    • Hopital Universitaire Robert Debre
  • Paris, France, 94270
    • Hôpital universitaire Kremlin-Bicètre
  • Pau, France
    • CH de Pau
  • Poissy, France, 78303
    • Centre Hospitalier Intercommunal Poissy-Saint Germain
  • Rennes, France, 35033
    • CHU Rennes
  • Rouen, France, 76000
    • CHU Charles Nicolle
  • Saint Etienne, France, 42270
    • CHU Saint Etienne
  • Strasbourg, France, 67098
    • CHU Strasbourg
  • Toulouse, France, 31059
    • Hôpital Paule de Viguier CHU Toulouse
  • Tours, France, 37044
    • Chu Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tranexamic acid; intravenous administration of 10-mL of tranexamic acid (EXACYL® 1 g/10 ml I.V., solution injectable)	Drug: Tranexamic Acid Injectable Solution; After the routine and prophylactic administration of a uterotonic , 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 woman within 3 minutes after birth, slowly (over 30-60 seconds), once the cord has been clamped.
Placebo Comparator: Chloride solution; sodium intravenous administration of 10-mL of chloride solution (0.9% -10mL).	Drug: Sodium Chloride 0.9%; After a routine and prophylactic administration of a uterotonic , 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 afterbirth), 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
postpartum hemorrhage	Incidence of PPH defined by a calculated blood loss > 1000mL [Calculated estimated blood loss = estimated blood volume × (preoperative Ht - postoperative Ht)/preoperative Ht (where estimated blood volume (mL) = weight (Kg) × 85)] or red blood cell transfusion up to day 2 postpartum. Preoperative Ht will be the most recent Ht within one week before delivery. Postoperative Ht will be measured at D2	day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mean calculated blood loss > 500mL		day 2
mean calculated blood loss > 1500mL		day 2
total mean calculated blood loss		day 2
mean gravimetrically estimated blood loss	by measuring the suction volume and swab weight; proportion of women requiring supplementary uterotonic treatment including sulprostone	6 hours
incidence of postpartum transfusion		day 2
Mean or median number of units of red blood cells transfused		day 2
incidence of arterial embolisation or emergency surgery for PPH		3 months
mean peripartum change in haemoglobin	difference between the most recent Hb within one week before delivery and at day 2 postpartum	day 2
mean peripartum change in hematocrit	difference between the most recent Ht within one week before delivery and at day 2 postpartum	day 2
heart rate	bpm	15, 30, 45, 60 and 120 minutes after delivery
diastolic blood pressure	mmHg	15, 30, 45, 60 and 120 minutes after delivery
systolic blood pressure	mmHg	15, 30, 45, 60 and 120 minutes after delivery
number of participants with nausea reported by caregivers		6 hours
number of participants with vomiting reported by caregivers		6 hours
number of participants with phosphenes reported by caregivers		6 hours
number of participants with dizziness reported by caregivers		6 hours
creatinemia	micromol/L	day 2
urea	g/L	day 2
prothrombin time (PT)		day 2
aspartate transaminase	IU/L	day 2
alanine transaminase	IU/L	day 2
total bilirubin	micromol/L	day 2
total fibrinogen	g/L	day 2
number of participants with deep venous thrombosis confirmed by paraclinical exams		within twelve weeks after the delivery
number of participants with pulmonary embolism confirmed by paraclinical exams		within twelve weeks after the delivery
number of participants with myocardial infarction confirmed by paraclinical exams		within twelve weeks after the delivery
number of participants with any thrombotic event confirmed by paraclinical exams		within twelve weeks after the delivery
seizure		within twelve weeks after the delivery
renal failure	defined by the need for dialysis	within twelve weeks after the delivery
women's satisfaction	assessed by a self-administered questionnaire	day 2 and weeks 8 postpartum
Provider-assessed clinically significant PPH		day 2
Hb drop > 2g/DL		day 2
Active prothrombin time (aPTT)		day 2
aspartate transaminase > 2N		day 2
alanine transaminase > 2N (day 2)		day 2
gravimetrically estimated blood loss > 500mL		day 2
gravimetrically estimated blood loss > 1000 mL		day 2
Shock		day 2
Transfer to Intensive Care Unit		twelve weeks after delivery
Death from any cause		42 days postpartum
supplementary uterotonic treatment	proportion of women requiring supplementary uterotonic treatment	day 2
iron sucrose perfusion	incidence of iron sucrose perfusion	discharge from hospital
mean gravimetrically estimated blood loss		at the end of the cesarean delivery

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: Ministry of Health, France

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2018
• Primary Completion (Actual): January 14, 2020
• Study Completion (Actual): April 8, 2020

Study Registration Dates

• First Submitted: January 30, 2018
• First Submitted That Met QC Criteria: February 12, 2018
• First Posted (Actual): February 13, 2018

Study Record Updates

• Last Update Posted (Actual): April 29, 2020
• Last Update Submitted That Met QC Criteria: April 28, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: prevention; Randomized; tranexamic acid; postpartum hemorrhage; cesarean; double blind placebo controlled trial
• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Postpartum Hemorrhage; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: CHUBX 2015/41

Drug and device information, study documents

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