Tranexamic Acid for Prevention of Postpartum Haemorrhage: a Dose-finding Study
Status:
Completed
Trial end date:
2019-08-19
Target enrollment:
Participant gender:
Summary
Published trials on tranexamic acid (TxA) for prevention have used a variety of fixed (0.5gm
or 1gm) and body-weight adjusted (10mg/kg or 15mg/kg) doses of TxA. Given the wide range of
bodyweights of pregnant women in contemporary obstetric practice, it is critical to determine
the minimum effective dose of TxA, so as to avoid under- or over-dosing. The rationale of
this study is to determine the minimum effective dose of TxA that is required to attain
therapeutic plasma levels of TxA, established at 5-15mg/L, following administration of a
single dose of intravenous (IV) TxA after childbirth and the clamping the umbilical cord, and
before delivery of the placenta. Following birth of the infant, and upon clamping the
umbilical cord, the investigators will administer a single dose of IV TxA in 100ml of 0.9%
sodium chloride at 50mg/min according to the dose-escalation schedule described below. The
slow rate of infusion has been chosen to prevent untoward effects such as hypotension that
have been noted when the rate of infusion has exceeded 100mg/min. As part of the
dose-escalation design, the investigators will start with 5mg/kg, half the smallest described
dose, on a sample of up to 5 women. They will continue to administer TxA doses in increments
of 5mg/kg to each successive batch of 5 women. If the number of treatment successes cannot
statistically rule out a value < 75% (< 4 of 5 women are successes due to values in the low
range), the dose will be increased by 5mg/kg for the next set of 5 women, and so on, until a
maximum dose of 30mg/kg is reached, a dose deemed safe based on earlier studies in different
populations. Once treatment success is determined at a certain dose, i.e. 4/5 women have
levels in the therapeutic range), a total of 20 women will be administered that dose to
ensure that 75% i.e. 18/20 women are successes at that dose.
Phase:
Phase 3
Details
Lead Sponsor:
Mount Sinai Hospital, Canada
Collaborators:
Canadian Institutes of Health Research (CIHR) Sinai Health System University Health Network, Toronto University of Toronto University of Waterloo