PPHPhase 4PROTECTNCT06025916
Postpartum Hemorrhage Reduction With Oral Tranexamic Acid: a Clinical Trial
A Phase 4 study testing Tranexamic acid in people with PPH, run by Karolinska Institutet at 1 site in Sweden.
Trial summary
This is a multicentre randomized placebo-controlled double-blinded phase IV study among 1000 women in Sweden and South Africa on the effect of oral tranexamic acid on PPH after vaginal delivery. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- PPH
- What is being tested?
- Tranexamic acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,000 participants
- Where
- 1 siteSweden
- Study dates
- 27 Sep 2023to Mar 2026
- Phase
- Phase 4
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Enrolled women will be ≥18 years, ≥36 gestational weeks, and planned for vaginal delivery. Women with known bleeding disorders, known allergy to TA, ongoing treatment for venous thrombosis, or inability to make an informed consent will be ineligible.
Who cannot join
- Opposite of above
Trial locations and contacts
1 site in 1 country.
Helena Paul contact
Sweden1 site, 1 recruiting
- Recruiting
Södersjukhuset (South General Hospital)
Stockholm, 118 83
Gita Strindfors, gita.strindfors@regionstockholm.se
About this study
Official title: Postpartum Hemorrhage Reduction With Oral Tranexamic Acid (PROTECT): a Multicenter Randomized Controlled Trial
This is a multicentre randomized placebo-controlled double-blinded phase IV study among 1000 women in Sweden and South Africa on the effect of oral tranexamic acid on PPH after vaginal delivery. The main purpose of the study is to evaluate the effect of orally administered tranexamic acid (TA) compared to placebo on rate of postpartum hemorrhage (PPH) after vaginal birth. Participants will be randomized to receive either 20 ml (2g) of the investigational medicinal product (TA100mg/ml) or 20ml of a placebo solution during labor. Our main endpoint, assessed at 24 hours after delivery is PPH defined as blood loss >=500ml and assessed both by weight and pre-postpartum hemoglobin (Hb) decrease >10 units difference in vaginal deliveries.
This RCT was preceded by a pilot intervention, included in the current protocol, aiming to assess uptake of oral forms of Tranexamic acid (TA) during active labour. The study took place at Södersjukhuset, Stockholm, Sweden between December 2022 and February 2023 among 51 women ≥ 36 gestational weeks with planned vaginal delivery who were randomized 1:1:1:1 to receive two grams of TA as oral solution, tablets, effervescent tablets, or 1g of intravenous (IV) TA, near full cervical dilatation. Blood samples were taken 30, 60, 120, 240, 360, and 480 minutes after TA administration. Plasma concentration of TA was measured using Liquid Chromatography-Tandem Mass Spectrometry. Mean values were compared between groups using ANOVA. Our main outcomes measures were time-to-therapeutic level, therapeutic interval, and maximum plasma concentration of TA.
Read the detailed description
Background Severe PPH is the leading cause of maternal death worldwide especially in developing countries. Preventing PPH before onset is of key importance because once bleeding starts it is difficult to control.Tranexamic acid (TA) is a well-established medication for treatment and prevention of heavy bleeding. Oral forms of TA are available over the counter in many settings. The effect of oral treatment in vaginal deliveries has however been little studied and is a stated research priority by the WHO. Oral TA is low-cost, stable at room temperature and easy to administer which makes it especially applicable to both low resource delivery settings and home- births.To prevent PPH, a therapeutic serum concentration of TA should coincide with the period immediately after delivery of the child, when the risk of PPH is greatest, meaning that TA should optimally be administered during the latter part of active labor.
The premises of the RCT are the following:
- The effect of oral prophylactic TA on rate of PPH is insufficiently known
- If oral TA is effective in preventing PPH, routine administration could reduce maternal morbidity significantly at low expense.
Methods Study population and inclusion criteria The study will include 1000 women planned for vaginal delivery at three study sites in Sweden (n=500) and two study sites in South Africa (n=500) during the period September 2023 to December 2026. Enrolled women will be ≥18 years, ≥36 gestational weeks, and planned for vaginal delivery. Women with known bleeding disorders, known allergy to TA, ongoing treatment for venous thrombosis, or inability to make an informed consent will be ineligible.
Setting and duration: The study will take place between September 2023 and December 2026 at three study sites in Sweden as well as Mowbray Maternity Hospital and Khayelitsha District Hospital in South Africa.
Recruitment and randomization We will recruit women during a routine or planned antenatal visit after 35 gestational weeks, or after admission to the delivery ward during the latency phase of labor or the early stages of labor.
Randomization will occur after a woman has been admitted to the labor ward with spontaneous onset of labor. Participants will be randomized to receive either 20 ml of the investigational medicinal product (TA) or 20ml of a placebo solution. The randomization sequence will be computer-generated by KTA (Karolinska Clinical Trial Alliance) and flasks with the IMP/placebo will be marked according to this sequence. Randomization will be 1:1 in permuted blocks of 10 to allow for block-sized deliveries to study sites. The placebo will be developed and manufactured by Apotek Produktion och Laboratorier (APL), Sweden, who will also supply the TA. Placebo and IMP flasks, in their randomization sequence will be transported in a temperature-validated delivery to a central laboratory in Cape Town through World Courier who specialises in research related distributions.
Intervention Our intervention consists of the oral self-intake of either 20 ml (2g) of oral solution of TA, 20 ml of placebo equivalent in appearance, odor and taste to the IMP, when the cervix is fully dilated.
Primary endpoints Weight-estimated rate of PPH (≥500ml)
Secondary endpoints Pre-postpartum Hb difference (g/L) ≥10 units Weight-estimated rate of severe PPH (≥1000ml) Mean blood loss (ml) Mean pre-postpartum Hb decrease (units Rate of blood transfusion (%) Feasibility (adherence to protocol) Acceptability of the treatment among participants and providers Thromboembolism up to 6 weeks postpartum
Study procedures Participants will experience three study procedures that would not necessarily occur had they not taken part in the study but all of which form part of routine care.
- A blood sample (hemoglobin, EVF, MCV, MCH, MCHC, LPC, TPC) taken at admission
- The oral intake of 20 ml IMP/placebo at full cervical dilatation
- Weighing of total blood loss (which is routine in many delivery settings)
- A blood sample including (hemoglobin, EVF, MCV, MCH, MCHC, LPC, TPC) taken after 24 hours (or prior to discharge should discharge occur before 24 hours)
- Conditions
- PPH
- Being tested
- Tranexamic acid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tranexamic acidDrug
Also called Cyklokapron
20 ml of oral solution TA (100mg/ml)
| Study group | Role | What they receive |
|---|---|---|
| Tranexamic acid | Active comparator | Will receive 20ml of tranexamic acid 100mg/ml at a timepoint when the cervix is dilated 6 cn (for multipara) and 8 cm for primipara Receives: Drug: Tranexamic acid |
| Placebo | Placebo comparator | Will receive 20ml of placebo solution, equivalent in appearance and taste to tranexamic acid solution but with no active ingredient, at a timepoint when the cervix is dilated 6 cn (for multipara) and 8 cm for primipara Receives: Drug: Tranexamic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
PPH
Proportion of participants with weight-assessed blood loss after delivery >/= 500ml
Measured: 24 hours
Secondary outcomes (9)
Severe PPH
Proportion of participants with blood loss after delivery >/= 1000ml
Measured: 24 hours
Blood transfusion
Proportion of participants receiving blood transfusion after vaginal birth
Measured: 72 hours
Mean blood loss
Mean blood loss after vaginal delivery (ml) among participants
Measured: 24 hours
Mean pre-post partal hemoglobin
Mean pre-post partal hemoglobin difference (units) among participants
Measured: 24 hours
Pre-post partal hemoglobin
Pre-post partal hemoglobin >/= 10 units among participants
Measured: 24 hours
Thromboembolism
Proportion of participants with thromboembolic event postpartum
Measured: 6 weeks after delivery
Feasibility of intervention
Proportion of participants taking TXA/placebo according to protocol
Measured: As specified in protocol
Acceptability for participants
Rate of no to minor discomfort upon administration of intervention (acceptability) among participants
Measured: Delivery and 24 hours after delivery
Acceptability for providers
Rate of no to minor disruption caused by administration of intervention (acceptability) experienced by providers
Measured: Delivery and 24 hours after delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2023
- Study start27 Sep 2023
- Primary completionDec 2025 (estimated)
- Study completionMar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PPHStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Stockholm South General Hospital, University of Cape Town
- Responsible party
- Principal investigator, Margit Endler, Karolinska Institutet
- Investigators
- Margit Endler, MD PhD, Associate Professor, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06025916
- Sponsor's protocol ID
- 2022-00327
- Acronym
- PROTECT
- Status last verified
- Sep 2024
- First submitted
- 29 Aug 2023
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Anonymized research data will be made available upon reasonable request
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Postpartum Hemorrhage Reduction With Oral Tranexamic Acid (PROTECT): a Multicenter Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06025916
- Acronym / sponsor ID
- PROTECT / 2022-00327
- Conditions
- PPH
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Stockholm South General Hospital, University of Cape Town
- Study start
- 27 Sep 2023 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Mar 2026 (estimated)
- First posted
- 6 Sep 2023 (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.
This is a multicentre randomized placebo-controlled double-blinded phase IV study among 1000 women in Sweden and South Africa on the effect of oral tranexamic acid on PPH after vaginal delivery. The main purpose of the study is to evaluate the effect of orally administered tranexamic acid (TA) compared to placebo on rate of postpartum hemorrhage (PPH) after vaginal birth. Participants will be randomized to receive either 20 ml (2g) of the investigational medicinal product (TA100mg/ml) or 20ml of a placebo solution during labor. Our main endpoint, assessed at 24 hours after delivery is PPH defined as blood loss >=500ml and assessed both by weight and pre-postpartum hemoglobin (Hb) decrease >10 units difference in vaginal deliveries.
This RCT was preceded by a pilot intervention, included in the current protocol, aiming to assess uptake of oral forms of Tranexamic acid (TA) during active labour. The study took place at Södersjukhuset, Stockholm, Sweden between December 2022 and February 2023 among 51 women ≥ 36 gestational weeks with planned vaginal delivery who were randomized 1:1:1:1 to receive two grams of TA as oral solution, tablets, effervescent tablets, or 1g of intravenous (IV) TA, near full cervical dilatation. Blood samples were taken 30, 60, 120, 240, 360, and 480 minutes after TA administration. Plasma concentration of TA was measured using Liquid Chromatography-Tandem Mass Spectrometry. Mean values were compared between groups using ANOVA. Our main outcomes measures were time-to-therapeutic level, therapeutic interval, and maximum plasma concentration of TA.
Detailed description
Background Severe PPH is the leading cause of maternal death worldwide especially in developing countries. Preventing PPH before onset is of key importance because once bleeding starts it is difficult to control.Tranexamic acid (TA) is a well-established medication for treatment and prevention of heavy bleeding. Oral forms of TA are available over the counter in many settings. The effect of oral treatment in vaginal deliveries has however been little studied and is a stated research priority by the WHO. Oral TA is low-cost, stable at room temperature and easy to administer which makes it especially applicable to both low resource delivery settings and home- births.To prevent PPH, a therapeutic serum concentration of TA should coincide with the period immediately after delivery of the child, when the risk of PPH is greatest, meaning that TA should optimally be administered during the latter part of active labor.
The premises of the RCT are the following:
- The effect of oral prophylactic TA on rate of PPH is insufficiently known
- If oral TA is effective in preventing PPH, routine administration could reduce maternal morbidity significantly at low expense.
Methods Study population and inclusion criteria The study will include 1000 women planned for vaginal delivery at three study sites in Sweden (n=500) and two study sites in South Africa (n=500) during the period September 2023 to December 2026. Enrolled women will be ≥18 years, ≥36 gestational weeks, and planned for vaginal delivery. Women with known bleeding disorders, known allergy to TA, ongoing treatment for venous thrombosis, or inability to make an informed consent will be ineligible.
Setting and duration: The study will take place between September 2023 and December 2026 at three study sites in Sweden as well as Mowbray Maternity Hospital and Khayelitsha District Hospital in South Africa.
Recruitment and randomization We will recruit women during a routine or planned antenatal visit after 35 gestational weeks, or after admission to the delivery ward during the latency phase of labor or the early stages of labor.
Randomization will occur after a woman has been admitted to the labor ward with spontaneous onset of labor. Participants will be randomized to receive either 20 ml of the investigational medicinal product (TA) or 20ml of a placebo solution. The randomization sequence will be computer-generated by KTA (Karolinska Clinical Trial Alliance) and flasks with the IMP/placebo will be marked according to this sequence. Randomization will be 1:1 in permuted blocks of 10 to allow for block-sized deliveries to study sites. The placebo will be developed and manufactured by Apotek Produktion och Laboratorier (APL), Sweden, who will also supply the TA. Placebo and IMP flasks, in their randomization sequence will be transported in a temperature-validated delivery to a central laboratory in Cape Town through World Courier who specialises in research related distributions.
Intervention Our intervention consists of the oral self-intake of either 20 ml (2g) of oral solution of TA, 20 ml of placebo equivalent in appearance, odor and taste to the IMP, when the cervix is fully dilated.
Primary endpoints Weight-estimated rate of PPH (≥500ml)
Secondary endpoints Pre-postpartum Hb difference (g/L) ≥10 units Weight-estimated rate of severe PPH (≥1000ml) Mean blood loss (ml) Mean pre-postpartum Hb decrease (units Rate of blood transfusion (%) Feasibility (adherence to protocol) Acceptability of the treatment among participants and providers Thromboembolism up to 6 weeks postpartum
Study procedures Participants will experience three study procedures that would not necessarily occur had they not taken part in the study but all of which form part of routine care.
- A blood sample (hemoglobin, EVF, MCV, MCH, MCHC, LPC, TPC) taken at admission
- The oral intake of 20 ml IMP/placebo at full cervical dilatation
- Weighing of total blood loss (which is routine in many delivery settings)
- A blood sample including (hemoglobin, EVF, MCV, MCH, MCHC, LPC, TPC) taken after 24 hours (or prior to discharge should discharge occur before 24 hours)
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tranexamic acid | Active comparator | Drug: Tranexamic acidWill receive 20ml of tranexamic acid 100mg/ml at a timepoint when the cervix is dilated 6 cn (for multipara) and 8 cm for primipara |
| Placebo | Placebo comparator | Drug: Tranexamic acidWill receive 20ml of placebo solution, equivalent in appearance and taste to tranexamic acid solution but with no active ingredient, at a timepoint when the cervix is dilated 6 cn (for multipara) and 8 cm for primipara |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Enrolled women will be ≥18 years, ≥36 gestational weeks, and planned for vaginal delivery. Women with known bleeding disorders, known allergy to TA, ongoing treatment for venous thrombosis, or inability to make an informed consent will be ineligible.
Key exclusion criteria (1 listed)
- Opposite of above
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: Cyklokapron20 ml of oral solution TA (100mg/ml) | Drug | Placebo, Tranexamic acid |
Primary outcome
PPH
Time frame: 24 hours
Proportion of participants with weight-assessed blood loss after delivery >/= 500ml
9 secondary outcomes
Severe PPH
Time frame: 24 hours
Blood transfusion
Time frame: 72 hours
Mean blood loss
Time frame: 24 hours
Mean pre-post partal hemoglobin
Time frame: 24 hours
Pre-post partal hemoglobin
Time frame: 24 hours
Thromboembolism
Time frame: 6 weeks after delivery
Feasibility of intervention
Time frame: As specified in protocol
Acceptability for participants
Time frame: Delivery and 24 hours after delivery
Acceptability for providers
Time frame: Delivery and 24 hours after delivery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Individual participant dataSharing planned: No. Anonymized research data will be made available upon reasonable request
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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.
Helena Paul contact
Margit Endler, MD PhD, Associate Professor principal investigator
Karolinska Institutet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tranexamic acid in people with PPH, run by Karolinska Institutet at 1 site in Sweden.
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 1 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 19 Sep 2024. 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 Sweden. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Margit Endler, MD PhD (0706747227, margit.endler@ki.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PPH (time frame: 24 hours). 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 19 Sep 2024.