Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03565276 |
| Other study ID # |
18-0001-A (MSH-REB) |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
July 11, 2018 |
| Est. completion date |
August 19, 2019 |
Study information
| Verified date |
September 2021 |
| Source |
Mount Sinai Hospital, Canada |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
Description:
Research question: What is the minimum effective dose required for attainment of therapeutic
plasma levels of 5-15mg/L in postpartum women?
Study design: Pharmacokinetic study using a dose-escalation design.
Trial treatment and dosage regimen: Following recruitment and prior to the caesarean
delivery, the anaesthesiologist will insert a large-bore cannula into the participant's
antecubital vein and draw blood for a complete blood count (CBC), which will be used in
tandem with 24-hour post-delivery CBC to estimate blood loss, and serum creatinine to rule
out elevated serum creatinine levels, a study exclusion criterion. Following birth of the
infant, and upon clamping the umbilical cord, the anaesthesiologist 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. All participants will receive oxytocin 20 international units (IU)
IV in 1 litre of 0.9% sodium chloride at the rate of 125 ml/hour with placental delivery, as
part of active management of the third stage of labour.
Endpoints Primary endpoints - Plasma levels of TxA: These will be obtained via serial blood
draws at baseline (before TxA administration), and at 15, 30, 60 minutes and 120 minutes
after administration of TxA, (as its maximum effect is within the 60 minutes and therapeutic
plasma concentrations are maintained for 7-8 hours after administration). Blood will be drawn
at baseline (before administration of TxA) in order to confirm zero plasma levels of TxA, as
part of quality assurance. Blood will be collected in a standard citrate tube (Vacutainer,
NJ, USA), centrifuged soon after collection and the plasma (supernatant) stored at -80°C
before analysis. TxA will be extracted from plasma using solid phase microextraction, and
concentrations measured using tandem liquid chromatography/mass spectrometry.
Secondary endpoints: (a) Total blood loss in 24 hours following childbirth will be determined
by the reference standard methods - direct measurement (blood collected in suction apparatus)
and gravimetric (weighing of linen) and by using formulae to determine blood loss using pre-
and post-delivery haemoglobin and haematocrit as we have previously described (b) Early
adverse events will be recorded prior to discharge and delayed events will be obtained at the
six-week postpartum visit or via phone call.
Expected duration of subject participation, duration of all trial periods and follow up: The
intervention will only be administered once, and blood drawn at baseline and 15, 30, 60 and
120 minutes after administration, as described above. Again, as described above, data on
early adverse events will be collected prior to discharge from hospital and those on delayed
adverse events will be obtained at the time of the routine 6-week postpartum visit in person
or via a telephone interview. There will be no additional follow up.
Stopping rules: As the drug will be administered as a slow infusion in the operating room, it
will be stopped immediately if any adverse events are noted. Thereafter, no further drug will
be administered, and therefore stopping rules do not apply. Participants will be allowed to
withdraw from the study at any point without affecting their clinical care.
