TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery

Postpartum Hemorrhage Clinical Trial

— TRAAP2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03431805
• Other study ID #: CHUBX 2015/41
• Status: Completed
• Phase: Phase 3
• Start date: March 3, 2018
• Est. completion date: April 8, 2020

Study information

• Verified date: April 2020
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4574
• Est. completion date: April 8, 2020
• Est. primary completion date: January 14, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 64 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hemorrhage
• Postpartum Hemorrhage

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	CHU Angers	Angers
France	CHU Jean Minjoz	Besançon
France	CHU Bordeaux	Bordeaux
France	CHRU Côte de Nacre	Caen
France	CHU Estain	Clermont Ferrand
France	Centre Hospitalier Intercommunal de Créteil	Créteil
France	Hopital Nord	Marseille
France	Hôpital Saint Joseph Marseille	Marseille
France	CHU de Montpellier	Montpellier
France	CHRU de Nancy	Nancy
France	CHU Nantes	Nantes
France	CHU Nîmes	Nîmes
France	Hôpital Saint Joseph Paris	Paris
France	Hôpital Trousseau	Paris
France	Hôpital universitaire Kremlin-Bicètre	Paris
France	Hôpital universitaire Necker-Enfants malades	Paris
France	Hôpital universitaire Robert Debré	Paris
France	Maternité de Port-Royal Paris	Paris
France	CH de Pau	Pau
France	Centre Hospitalier Intercommunal Poissy-Saint Germain	Poissy
France	CHU Rennes	Rennes
France	CHU Charles Nicolle	Rouen
France	CHU Saint Etienne	Saint Etienne
France	CHU Strasbourg	Strasbourg
France	Hôpital Paule de Viguier CHU Toulouse	Toulouse
France	CHU Tours	Tours

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

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