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Postpartum Hemorrhage Reduction With Oral Tranexamic Acid: a Clinical Trial (PROTECT)

Primary Purpose

PPH

Status
Recruiting
Phase
Phase 4
Locations
Sweden
Study Type
Interventional
Intervention
Tranexamic acid
Sponsored by
Karolinska Institutet
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for PPH

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria: 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. Exclusion Criteria: Opposite of above

Sites / Locations

  • Södersjukhuset (South General Hospital)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Tranexamic acid

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

PPH
Proportion of participants with weight-assessed blood loss after delivery >/= 500ml

Secondary Outcome Measures

Severe PPH
Proportion of participants with blood loss after delivery >/= 1000ml
Blood transfusion
Proportion of participants receiving blood transfusion after vaginal birth
Mean blood loss
Mean blood loss after vaginal delivery (ml) among participants
Mean pre-post partal hemoglobin
Mean pre-post partal hemoglobin difference (units) among participants
Pre-post partal hemoglobin
Pre-post partal hemoglobin >/= 10 units among participants
Thromboembolism
Proportion of participants with thromboembolic event postpartum
Feasibility of intervention
Proportion of participants taking TXA/placebo according to protocol
Acceptability for participants
Rate of no to minor discomfort upon administration of intervention (acceptability) among participants
Acceptability for providers
Rate of no to minor disruption caused by administration of intervention (acceptability) experienced by providers

Full Information

First Posted
August 29, 2023
Last Updated
October 10, 2023
Sponsor
Karolinska Institutet
Collaborators
Stockholm South General Hospital, University of Cape Town
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1. Study Identification

Unique Protocol Identification Number
NCT06025916
Brief Title
Postpartum Hemorrhage Reduction With Oral Tranexamic Acid: a Clinical Trial
Acronym
PROTECT
Official Title
Postpartum Hemorrhage Reduction With Oral Tranexamic Acid (PROTECT): a Multicenter Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 27, 2023 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
March 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Karolinska Institutet
Collaborators
Stockholm South General Hospital, University of Cape Town

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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. 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
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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PPH

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
1000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Tranexamic acid
Arm Type
Active Comparator
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Tranexamic acid
Other Intervention Name(s)
Cyklokapron
Intervention Description
20 ml of oral solution TA (100mg/ml)
Primary Outcome Measure Information:
Title
PPH
Description
Proportion of participants with weight-assessed blood loss after delivery >/= 500ml
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Severe PPH
Description
Proportion of participants with blood loss after delivery >/= 1000ml
Time Frame
24 hours
Title
Blood transfusion
Description
Proportion of participants receiving blood transfusion after vaginal birth
Time Frame
72 hours
Title
Mean blood loss
Description
Mean blood loss after vaginal delivery (ml) among participants
Time Frame
24 hours
Title
Mean pre-post partal hemoglobin
Description
Mean pre-post partal hemoglobin difference (units) among participants
Time Frame
24 hours
Title
Pre-post partal hemoglobin
Description
Pre-post partal hemoglobin >/= 10 units among participants
Time Frame
24 hours
Title
Thromboembolism
Description
Proportion of participants with thromboembolic event postpartum
Time Frame
6 weeks after delivery
Title
Feasibility of intervention
Description
Proportion of participants taking TXA/placebo according to protocol
Time Frame
As specified in protocol
Title
Acceptability for participants
Description
Rate of no to minor discomfort upon administration of intervention (acceptability) among participants
Time Frame
Delivery and 24 hours after delivery
Title
Acceptability for providers
Description
Rate of no to minor disruption caused by administration of intervention (acceptability) experienced by providers
Time Frame
Delivery and 24 hours after delivery

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: Opposite of above
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Margit Endler, MD PhD
Phone
0706747227
Email
margit.endler@ki.se
First Name & Middle Initial & Last Name or Official Title & Degree
Helena Paul
Email
helena.paul@regionstockholm.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Margit Endler, MD PhD, Associate Professor
Organizational Affiliation
Karolinska Institutet
Official's Role
Principal Investigator
Facility Information:
Facility Name
Södersjukhuset (South General Hospital)
City
Stockholm
ZIP/Postal Code
118 83
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gita Strindfors
Email
gita.strindfors@regionstockholm.se

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Anonymized research data will be made available upon reasonable request

Learn more about this trial

Postpartum Hemorrhage Reduction With Oral Tranexamic Acid: a Clinical Trial

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