Discussion
participationEligibility, seizure, dizziness, PPH, nausea, vomiting
ADVERSE EVENTS, PREGNANCY RELATED, RECRUITMENT, THROMBOEMBOLISM
Our pilot trial exceeded the primary feasibility target of > 85% or randomized patients receiving IP (89%). Three randomized patients (1 TXA, 2 placebo) did not receive IP as they delivered spontaneously before the IP could be administered. In contrast, previous studies administering TXA at the same timepoint for vaginal delivery (delivery of the anterior shoulder), did not report any protocol deviations of randomized patients not receiving TXARecruitment for randomized controlled trials is frequently challenging, particularly for those involving pregnant women, who have unique concerns regarding participationEligibility criteria can seemingly be eliminated as a contributing factor, as our criteria were more inclusive than previous studies (e.g. not requiring a cephalic presentation) attempting to maximize generalizability. One potential factor is resource and logistical limitations as restricting enrolment to patients delivering between 07h00 and 23h00, resulted in 5/35 (14%) of consented patients not being randomized. Around the clock availability of research personnel is cost prohibitive (~ $100,000 per year) and beyond the available resources for TAPPH-1. However, even taking these factors into account, the number of eligible patients who were approached, but did not consent was particularly high (94%). A likely explanation for this is differences in the recruitment reality, including differences in research culture or regulatory burden, observed in Canada or North America as a whole, compared to Europe or non-high HDI countries. A follow-up study to further explore the reasons for recruitment challenges is being considered.The TRAAP study concluded that the relative risk of provider-assessed clinically significant PPH was lower in the TXA group although the primary outcome of PPH (determined quantitatively) was not significant (p = 0.07). The TRAAP trial also reported no significant difference in serious adverse events, including thromboembolism, seizure, or re-admission to hospital, although rates of nausea, vomiting and dizziness were higher with TXA. Notably, the TRAAP study only included patients delivering vaginally, limiting its generalizability, and necessitating further trials to address the large population of women who undergo CD. The follow-up study (TRAAP2) published in April 2021 by the same group randomizing 4551 women undergoing CD identified a relative risk of PPH of 0.84 (95% CI 0.75–0.94, p = 0.003) in those administered TXADespite apparent similarities in risk factors and incidence of PPH between Canada and FranceThe generalizability of this trial is limited by its single centre nature. The regulatory environment within Canada is such that the specific Health Canada requirements for off-label trials would be applicable to any centre within Canada. Our institution is also a high-risk obstetric centre, and the study sample was recruited from a population with a higher prevalence of medical or pregnancy related issues and as such may also limit generalizability and our estimation of feasibility. Furthermore, because of a lack of 24-h coverage, our study also would not be applicable for emergency cases.