Tranexamic Acid for Preventing Postpartum Haemorrhage Following a Vaginal Delivery (TRAAP)

University Hospital, Angers

Status and phase

Completed

Phase 3

Conditions

Immediate Postpartum Hemorrhage

Treatments

Drug: Tranexamic Acid

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT02302456

PHRC 2013-01

Details and patient eligibility

About

The purpose of this study is to assess whether the administration of a low dose of tranexamic acid just after vaginal delivery can reduce the incidence of immediate postpartum hemorrhage, in women who receive a prophylactic administration of oxytocin.

Full description

Postpartum hemorrhage (PPH) is a major cause of maternal mortality, accounting for one quarter of all maternal deaths worldwide. Its incidence estimates in the literature vary widely, from 3% to 15% of deliveries. Uterotonics after birth are the only intervention that has been shown to be effective for PPH prevention. Tranexamic acid (TXA), an antifibrinolytic agent, has therefore been investigated as a potentially useful complement to uterotonics for prevention because it has been proved to reduce blood loss in elective surgery, bleeding in trauma patients, and menstrual blood loss. Randomized controlled trials for PPH prevention after cesarean (n=10) and vaginal (n=2) deliveries showed that women who had received TXA had a significantly lesser amount of postpartum blood loss without any increase in severe maternal adverse effect. However, overall, the quality of these trials was poor, and they were not designed to test the effect of TXA on the reduction of PPH incidence, nor on the incidence of rare but severe adverse effects. Large, adequately powered multicenter randomized controlled trials are required before the widespread use of TXA for preventing PPH can be recommended.

The investigators propose a multicentre randomised, double-blind, placebo-controlled trial, with two parallel groups.

Individual information on the trial will be provided to women in late pregnancy during prenatal visits. This information will be repeated when the women arrive in the delivery room; the women then will confirm their participation and provide informed written consent before delivery, when, in the opinion of the investigator, the woman is likely to have a vaginal delivery with a minimum of 4 cm of cervix dilatation.

The intervention will be the intravenous administration of a 10-ml blinded ampoule of the study drug (either 1g TXA or placebo according to the randomisation order), slowly (over 30-60 seconds), within 2 minutes after birth and prophylactic oxytocin administration, and once the cord has been clamped.

All other aspects of management of the third stage will be identical in both arms:

Routine prophylactic intravenous injection of 5 IU oxytocin at delivery of the anterior shoulder or within 2 minutes after birth
Placement of a graduated (100 mL graduation) collector bag just after birth, left in place until the birth attendant judges that bleeding has stopped, and always at least for 15 minutes. When a woman is included in the trial, a bag will be prepared and ready to be put in place as soon as the baby is born and placed on the mother's belly; if needed, a second staff person will be present to help in managing both the baby and the bag. This will make it possible to collect and measure vaginal blood loss objectively during the immediate postpartum.
Manual removal of the placenta at 30 minutes after birth if not expelled in absence of bleeding.
Rapid suturing of the episiotomy, in accordance with good clinical practices
Systematic use of uterotonic drugs after third stage of labor is not recommended.
Controlled cord traction (CCT) will be left at the discretion of the practitioner.

If PPH occurs, standardised management will be provided according to the department's protocol. In particular, the use of TXA for the treatment of PPH will be allowed and left at the discretion of the practitioner according to the department's protocol.

The duration of the participation of each patient included in the trial will be from inclusion through 3 months postpartum.

The planned total duration of the trial will be 34 months including 23 months of patient inclusion

Enrollment

4,079 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age≥ 18 years
Planned vaginal delivery
Term ≥ 35 weeks of gestation
Singleton pregnancy
Informed consent form signed

Exclusion criteria

History of venous (deep vein thrombosis and/or pulmonary embolism) or arterial (angina pectoris, myocardial infarction, stroke) thrombosis.
History of epilepsy or seizure
Any known cardiovascular, renal, liver disorders
Auto-immune disease
Sickle cell disease
Severe hemorrhagic disease
Placenta previa
Abnormally invasive placenta (placenta accreta/increta/percreta)
Abruptio placentae
Eclampsia; hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome
Multiple pregnancy
In utero foetal death
Administration of Low-Molecular-Weight Heparin or antiplatelet agents seven days before delivery
Poor understanding of the French language