Prophylactic use of the antifibrinolytic drug tranexamic acid during cesarean delivery was associated with significantly less postpartum hemorrhage compared to placebo in a newly reported multicenter trial from France, but researchers characterized the clinical relevance of the difference as “questionable.”
Tranexamic acid has emerged in recent years as an alternative to oxytocin, misoprostol, and other widely used uterotonic drugs for the prevention of blood loss following childbirth, with several small, single-center trials suggesting a benefit for preventing blood loss in women undergoing elective surgical delivery.
In the multicenter study, published online April 28 in The New England Journal of Medicine, researcher Loic Sentilhes, MD, PhD, of Bordeaux University, Bordeaux, France, and colleagues, wrote that the prophylactic use of tranexamic acid at cesarean delivery showed “a biologic effect, in that the calculated estimated blood loss was significantly lower among women who received the drug than among those who received placebo,” which was attributed to significantly smaller decreases in hematocrit from before to after surgery.
The mean between-group difference was approximately 100 ml in the study, which included more than 4,000 women who underwent cesarean deliveries.
The researchers concluded that the clinical relevance of this narrow difference was “questionable” since there were not significant between-group differences in the secondary study outcomes of gravimetrically estimated blood loss, provider-assessed clinically significant postpartum hemorrhage, use of additional uterotonic agents, and postpartum blood transfusion.
“Our results contrast with findings of meta-analyses of summary data from small, single-center, randomized trials, which have shown that tranexamic acid administration at cesarean delivery resulted in significantly less mean gravimetrically estimated blood loss, as well as in less frequent blood loss exceeding 500 ml and 1,000 ml, less frequent use of uterotonic agents, and less frequent transfusions than placebo or no treatment,” Sentilhes et al wrote.
In the meta-analyses, prophylactic tranexamic acid use was associated with a 45% to 75% lower risk for these complications.
The multicenter, double-blind Tranexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery (TRAAP2) trial included pregnant women expected to undergo cesarean delivery recruited from 27 maternity hospitals in France.
The women were randomized 1:1 to receive either tranexamic acid (1 g) or placebo, and the primary study outcome was postpartum hemorrhage, defined as a calculated estimated blood loss greater than 1,000 ml or receipt of a red-cell transfusion within two days following delivery.
Of 4,551 women who underwent randomization, 4,431 had a cesarean delivery and 4,153 (93.7%) had primary outcome data available.
Among the main findings:
- The primary outcome occurred in 556 of 2,086 women (26.7%) who received tranexamic acid and in 653 of 2,067 women (31.6%) in the placebo group (adjusted risk ratio, 0.84; 95% CI, 0.75-0.94; P=0.003).
- No significant between-group differences were seen in the secondary outcomes of mean gravimetrically estimated blood loss and the percentage of women with provider-assessed clinically significant postpartum hemorrhage, use of additional uterotonic agents, or postpartum blood transfusion.
- Thromboembolic events in the three months following delivery occurred in 0.4% of women treated with tranexamic acid and 0.1% of women in the placebo group (adjusted risk ratio, 4.01; 95% CI, 0.85-18.92; P=0.08).
“Our trial included a large population of women who underwent cesarean delivery, and one third of these procedures were performed during labor; our trial also had few exclusion criteria,” the researchers wrote, adding that “the results are thus likely to be generalizable to women who undergo cesarean delivery in a similar context of care.”
They noted that blood loss for the primary outcome was assessed using an objective, validated calculation based on postoperative and preoperative hematocrit, and that the latter value was measured no more than 8 days prior to delivery in order to standardize the timing of measurement “and avoid heterogeneity due to possible third-trimester changes.”
Study limitations cited by the researchers included the lack of power to detect “potentially meaningful differences in the risk of severe maternal complication, such as transfusion.”
The incidence of the primary outcome was also twice as high as expected, which the researchers attributed to the inclusion of women who had cesarean deliveries during labor. In addition, one in four women in the study did not receive tranexamic acid or placebo within three minutes after delivery, as specified by the study protocol.
-
Prophylactic use of tranexamic acid during cesarean delivery was associated with significantly less postpartum hemorrhage compared to placebo following cesarean section.
-
Researchers characterized the clinical relevance of the difference in outcomes between the tranexamic acid and placebo groups as “questionable.”
Salynn Boyles, Contributing Writer, BreakingMED™
The study was supported by a grant from the French Ministry of Health under its Clinical Research Hospital Program.
Sentilhes reported receiving lecture fees from Bayer, GlaxoSmithKline, and Sigvaris and lecture fees and consulting fees from Ferring Pharmaceuticals.
Cat ID: 191
Topic ID: 83,191,730,191,41,192,925
