Post Partum HemorrhagePhase 3NCT03565276
Tranexamic Acid for Prevention of Postpartum Haemorrhage: a Dose-finding Study
A Phase 3 study testing Tranexamic Acid in people with Post Partum Hemorrhage, run by Mount Sinai Hospital, Canada at 1 site in Canada.
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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Post Partum Hemorrhage
- What is being tested?
- Tranexamic Acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteCanada
- Study dates
- 11 Jul 2018to 19 Aug 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women 18 years of age or greater
- Pregnant with a single fetus
- Undergoing planned caesarean delivery for a non-medical indication
- ≥ 37 completed weeks of gestation
Who cannot join
- Contraindications to use of TxA (i.e. acute arterial/venous thrombosis, hypersensitivity to TxA, history of seizures, moderate to severe renal failure from any condition, defective colour vision, subarachnoid haemorrhage and disseminated intravascular coagulation (abnormally increased activation of pro-coagulant pathways))
- Medical conditions that could influence bleeding and/or the pharmacokinetics of TxA (i.e. personal/family history of bleeding disorders, receipt of warfarin seven days or heparin 24 hours prior to caesarean delivery, hypertensive disorders of pregnancy, need for intra- or post-operative blood transfusions and postpartum thromboprophylaxis)
- Women with morbidly adherent placentae scheduled for planned caesarean-hysterectomies
- Use of concomitant medications that could result in drug interactions (hydrochlorothiazide, desmopressin, sulbactam-ampicillin, carbazochrome, ranitidine or nitroglycerin)
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed 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.
- Conditions
- Post Partum Hemorrhage
- Being tested
- Tranexamic Acid
- Keywords
- Post partum hemorrhage, Tranexamic acid, TXA, Dose-finding, Prevention
- Medical subject headings
- Postpartum Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tranexamic AcidDrug
Also called TxA, Cyklokapron
A single dose of intravenous TxA in 100ml of 0.9% sodium chloride at 50mg/min, via a dose-escalation design
| Study group | Role | What they receive |
|---|---|---|
| Experimental: TXA | Experimental | Intravenous Tranexamic Acid beginning at 5mg/kg administered as part of a dose-escalation design. Receives: Drug: Tranexamic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma levels of TxA
Measured in mg/L. The 3 samples drawn at 15, 30 and 60 minutes should be between 5-15mg/L to be considered treatment success. Levels at 0 minutes is expected to be zero and 120 minutes expected to be sub-therapeutic.
Measured: 0, 15, 30, 60, 120 minutes
Secondary outcomes (2)
Early Adverse events
Having experienced any one of the following: nausea/vomiting, abdominal pain, diarrhoea, disturbed color vision, skin rash, headache, migraine, nasal/sinus symptoms, musculoskeletal/back pain, joint pains, muscle cramps, fatigue, anorexia, dizziness, seizures, blood clots or low blood pressure between delivery and discharge from hospital.
Measured: maximum 24 hours
Early adverse event 2 - Ga
Having experienced any one of the early adverse outcomes described above between discharge from hospital and the six-week postpartum visit
Measured: six weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2018
- Study start11 Jul 2018
- Primary completion14 Mar 2019
- Study completion19 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post Partum HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mount Sinai Hospital, Canada
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Sinai Health System, University of Toronto, University of Waterloo, University Health Network, Toronto
- Responsible party
- Principal investigator, Rohan D'Souza, Mount Sinai Hospital, Canada
- Investigators
- Rohan D'Souza, Principal investigator, Rohan.Dsouza@sinaihealthsystem.ca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03565276
- Sponsor's protocol ID
- 18-0001-A (MSH-REB)
- Status last verified
- Sep 2021
- First submitted
- 23 Apr 2018
- Last updated
- 23 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tranexamic Acid for Prevention of Postpartum Haemorrhage: a Dose-finding Study
- ClinicalTrials.gov ID
- NCT03565276
- Acronym / sponsor ID
- 18-0001-A (MSH-REB)
- Conditions
- Post Partum Hemorrhage
- Keywords
- Post partum hemorrhage, Tranexamic acid, TXA, Dose-finding, Prevention
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Mount Sinai Hospital, CanadaUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Sinai Health System, University of Toronto, University of Waterloo, University Health Network, Toronto
- Study start
- 11 Jul 2018 (actual)
- Primary completion
- 14 Mar 2019 (actual)
- Study completion
- 19 Aug 2019 (actual)
- First posted
- 21 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Experimental: TXA | Experimental | Drug: Tranexamic AcidIntravenous Tranexamic Acid beginning at 5mg/kg administered as part of a dose-escalation design. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Women 18 years of age or greater
- Pregnant with a single fetus
- Undergoing planned caesarean delivery for a non-medical indication
- ≥ 37 completed weeks of gestation
Key exclusion criteria (4 listed)
- Contraindications to use of TxA (i.e. acute arterial/venous thrombosis, hypersensitivity to TxA, history of seizures, moderate to severe renal failure from any condition, defective colour vision, subarachnoid haemorrhage and disseminated intravascular coagulation (abnormally increased activation of pro-coagulant pathways))
- Medical conditions that could influence bleeding and/or the pharmacokinetics of TxA (i.e. personal/family history of bleeding disorders, receipt of warfarin seven days or heparin 24 hours prior to caesarean delivery, hypertensive disorders of pregnancy, need for intra- or post-operative blood transfusions and postpartum thromboprophylaxis)
- Women with morbidly adherent placentae scheduled for planned caesarean-hysterectomies
- Use of concomitant medications that could result in drug interactions (hydrochlorothiazide, desmopressin, sulbactam-ampicillin, carbazochrome, ranitidine or nitroglycerin)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tranexamic AcidAlso: TxA, CyklokapronA single dose of intravenous TxA in 100ml of 0.9% sodium chloride at 50mg/min, via a dose-escalation design | Drug | Experimental: TXA |
Primary outcome
Plasma levels of TxA
Time frame: 0, 15, 30, 60, 120 minutes
Measured in mg/L. The 3 samples drawn at 15, 30 and 60 minutes should be between 5-15mg/L to be considered treatment success. Levels at 0 minutes is expected to be zero and 120 minutes expected to be sub-therapeutic.
2 secondary outcomes
Early Adverse events
Time frame: maximum 24 hours
Early adverse event 2 - Ga
Time frame: six weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2021.
- Individual participant dataSharing planned: No
Related trials for Post Partum Hemorrhage
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Measured Versus Hemoglobin-Calculated Postpartum Blood Loss in Waterbirth
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Long Term Outcome After Use of Vacuum-induced Tamponade for Postpartum Hemorrhage
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Prevention of Postpartum Hemorrhage With Tranexamic Acid
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rohan D'Souza principal investigator
Rohan.Dsouza@sinaihealthsystem.ca
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tranexamic Acid in people with Post Partum Hemorrhage, run by Mount Sinai Hospital, Canada at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma levels of TxA (time frame: 0, 15, 30, 60, 120 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2021.