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CompletedNCT04733157ETAPPHUpdated Mar 20, 2023Results posted

The Efficacy of Tranexamic Acid in Preventing Postpartum Haemorrhage After Caesarean Section

A Phase 3 interventional study of Tranexamic acid injection and Normal saline placebo in Postpartum Hemorrhage, sponsored by University of Zimbabwe. Completed at 2 sites in Zimbabwe. Open to female participants. Per ClinicalTrials.gov, last updated 2023-03-20.

Sponsored by University of Zimbabwe · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
1,226
Allocation
Randomized
Sex
Female
01

Study summary

This study seeks to determine if the using tranexamic acid prophylactically at caesarean section will prevent postpartum haemorrhage which is a major cause of maternal mortality in Zimbabwe and globally.

Read the detailed description

This trial will be an placebo-controlled, two-centre, randomized control trial with two parallel groups including 1,162 women who undergo elective or emergency caesarean deliveries at term. The study group will receive tranexamic acid (TXA) 1g intravenously at the onset of skin incision. There is normal saline placebo for the control group. The study and control groups will both receive the standard care offered at caesarean section including 5 IU of oxytocin intravenously on delivery of the baby. .

02

Conditions studied

  • Postpartum Hemorrhage

Keywords

  • Postpartum hemorrhage
  • Tranexamic acid
  • Caesarean section
  • Prevent
03

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
Female
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria: Women undergoing elective or emergency caesarean section with:

  • Estimated gestational age of 37 weeks or more
  • Live intrauterine foetus
  • Elective or emergency caesarean delivery
  • Signed informed consent

Exclusion Criteria:

  • History of coagulopathies or conditions predisposing them to thromboembolic phenomena,
  • seizure history,
  • autoimmune disease,
  • placental abruption,
  • placenta praevia,
  • abnormally adherent placentae if identified on prenatal ultrasound,
  • eclampsia or HELLP syndrome,
  • known hypersensitivity to TXA,
  • planned general anaesthesia,
  • caesarean delivery for the second twin or second/third triplet(s) after vaginal birth of the first twin,
  • poor understanding of English/Shona languages,
  • those who have received anticoagulants in the week before delivery
  • persons-under-investigation for Coronavirus disease (COVID-19) and confirmed COVID-19 positive women
04

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Care provider)
Enrollment
1,226 participants (actual)

Study arms

  • Experimental
    Study group/Group A

    The study group will receive TXA 1g intravenously at the onset of skin incision.

    Drug: Tranexamic acid injection

  • Placebo comparator
    Control group/Group B

    There is an equivalent volume of normal saline for the control group.

    Other: Normal saline placebo

Interventions

  • DrugTranexamic acid injection

    Tranexamic 1g administered intravenously at the onset of skin incision at caesarean section

    Also known as: TXA

  • OtherNormal saline placebo

    10ml of normal saline will be administered intravenously at onset of skin incision at caesarean section to the placebo group

05

What researchers measure

Primary outcomes

  1. Number of Participants With Postpartum Hemorrhage (PPH)

    Calculated estimated blood loss exceeding 1000ml. Estimated Blood Loss (EBL) was calculated using laboratory values of hemoglobin levels before and after procedure. Postpartum hemorrhage is defined as blood loss exceeding 1000mL after cesarean section.

    Time frame: Up to day 2 postpartum

Secondary outcomes

  1. Blood Loss Using Hemoglobin Values

    Calculated blood loss using hemoglobin values. A mean value of blood loss calculated using hemoglobin values

    Time frame: Up to day 2 postpartum

  2. Mean Blood Loss as Estimated by Obstetrician

    Visually estimated blood loss at time of caesarean section. Attending obstetrician gave an estimated value of blood loss after delivery.

    Time frame: 2 hours

  3. Occurrence of Postpartum Shock

    Number of participants who had hypovolemic shock related to PPH as determined by assessing BP and pulse.

    Time frame: Up to day 2 postpartum

  4. Use of Supplementary Uterotonic(s)

    Number of women requiring supplementary uterotonics

    Time frame: Up to day 2 postpartum

  5. Postpartum Transfusion

    Number of women given postpartum transfusion

    Time frame: Up to day 2 postpartum

  6. Emergency Surgery for PPH

    Number of participants who had emergency surgery for PPH including caesarean hysterectomies

    Time frame: Up to day 2 postpartum

  7. Change in Peripartum Haemoglobin

    Mean change in haemoglobin concentration between the study group, calculated hemoglobin values at day 2 postpartum minus baseline hemoglobin values.

    Time frame: Up to day 2 postpartum

  8. Number of Participants With a Decrease in Peripartum Hemoglobin

    Number of participants with a drop in hemoglobin more than 2g/dL or less than 2g/dL

    Time frame: Up to day 2 postpartum

  9. Change in Peripartum Haematocrit

    Mean change in haematocrit percentage between the study groups from baseline to day 2 postpartum

    Time frame: Up to day 2 postpartum

  10. Admission Into Intensive Care Unit

    Number of participants transferred to intensive care unit

    Time frame: Up to day 2 postpartum

  11. Death From Any Cause

    Number of participants who died from any cause

    Time frame: Up to date of death or day 4 from admission

  12. Blood Pressure Measurements

    Blood pressure at 15, 30, 45, 60, and 120 min after delivery

    Time frame: Up to 2 hours after the caesarean section

  13. Number of Mild Adverse Events

    Number of mild events of nausea, vomiting, sensation of rings or spots of light in the visual field, dizziness

    Time frame: Up to 24 hours after administration

  14. Number of Severe Adverse Events

    * Deep vein thrombosis (if the diagnosis is confirmed by Doppler ultrasound) * Pulmonary embolism (if the diagnosis is confirmed by radiological examination) * Myocardial infarction * Seizure * Renal failure requiring dialysis

    Time frame: Up to day 3 postpartum

  15. Any Other Unexpected Adverse Event

    Number of unexpected events during and after the adminstration of study drug and duration of observation

    Time frame: Up to day 3 postpartum

  16. Length of Hospital Stay

    Duration of hospital admission in days

    Time frame: Up to day 3 postpartum

06

Results

Posted Mar 20, 2023

Participant flow

Participant flow — Overall Study
MilestoneStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
Started613613
Completed611613
Not completed20

Outcome measures

PrimaryNumber of Participants With Postpartum Hemorrhage (PPH)

Calculated estimated blood loss exceeding 1000ml. Estimated Blood Loss (EBL) was calculated using laboratory values of hemoglobin levels before and after procedure. Postpartum hemorrhage is defined as blood loss exceeding 1000mL after cesarean section.

Time frame:
Up to day 2 postpartum
Reported as:
Count of participants · Participants
Number of Participants With Postpartum Hemorrhage (PPH)
ParticipantsStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
Did not have PPH (blood loss <1000 mL)409399
Had PPH (blood loss >=1000 mL)111125
Statistical analysis
  • Study Group/Group A_(Tranexamic Acid) vs Control Group/Group B_(Placebo) · Chi-squared · p = 0.33 (Threshold for statistical significance was 0.05) · Risk ratio (rr): 0.87 · 95% CI 0.69 to 1.09
SecondaryBlood Loss Using Hemoglobin Values

Calculated blood loss using hemoglobin values. A mean value of blood loss calculated using hemoglobin values

Time frame:
Up to day 2 postpartum
Reported as:
Mean · mL
Blood Loss Using Hemoglobin Values
mLStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
Blood Loss Using Hemoglobin Values537.2 ± 758.2528.6 ± 1020.9
SecondaryMean Blood Loss as Estimated by Obstetrician

Visually estimated blood loss at time of caesarean section. Attending obstetrician gave an estimated value of blood loss after delivery.

Time frame:
2 hours
Reported as:
Mean · mL
Mean Blood Loss as Estimated by Obstetrician
mLStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
Mean Blood Loss as Estimated by Obstetrician501.2 ± 209.8495.0 ± 188.8
SecondaryOccurrence of Postpartum Shock

Number of participants who had hypovolemic shock related to PPH as determined by assessing BP and pulse.

Time frame:
Up to day 2 postpartum
Reported as:
Count of participants · Participants
Occurrence of Postpartum Shock
ParticipantsStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
No postpartum shock603611
Postpartum shock82
SecondaryUse of Supplementary Uterotonic(s)

Number of women requiring supplementary uterotonics

Time frame:
Up to day 2 postpartum
Reported as:
Count of participants · Participants
Use of Supplementary Uterotonic(s)
ParticipantsStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
No supplementary uterotonic9374
Supplementary uterotonic given252232
SecondaryPostpartum Transfusion

Number of women given postpartum transfusion

Time frame:
Up to day 2 postpartum
Reported as:
Count of participants · Participants
Postpartum Transfusion
ParticipantsStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
transfusion given89
no transfusion given603604
SecondaryEmergency Surgery for PPH

Number of participants who had emergency surgery for PPH including caesarean hysterectomies

Time frame:
Up to day 2 postpartum
Reported as:
Count of participants · Participants
Emergency Surgery for PPH
ParticipantsStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
No emergency surgery603601
Emergency Surgery done44
SecondaryChange in Peripartum Haemoglobin

Mean change in haemoglobin concentration between the study group, calculated hemoglobin values at day 2 postpartum minus baseline hemoglobin values.

Time frame:
Up to day 2 postpartum
Reported as:
Mean · g/dL
Change in Peripartum Haemoglobin
g/dLStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
Change in Peripartum Haemoglobin1.1 ± 1.41.16 ± 1.7
SecondaryNumber of Participants With a Decrease in Peripartum Hemoglobin

Number of participants with a drop in hemoglobin more than 2g/dL or less than 2g/dL

Time frame:
Up to day 2 postpartum
Reported as:
Count of participants · Participants
Number of Participants With a Decrease in Peripartum Hemoglobin
ParticipantsStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
drop less than 2g/dl438442
drop greater than or equal to 2g/dl117125
SecondaryChange in Peripartum Haematocrit

Mean change in haematocrit percentage between the study groups from baseline to day 2 postpartum

Time frame:
Up to day 2 postpartum
Reported as:
Mean · percent of hematocrit change
Change in Peripartum Haematocrit
percent of hematocrit changeStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
Change in Peripartum Haematocrit3.8 ± 4.63.6 ± 4.6
SecondaryAdmission Into Intensive Care Unit

Number of participants transferred to intensive care unit

Time frame:
Up to day 2 postpartum
Reported as:
Count of participants · Participants
Admission Into Intensive Care Unit
ParticipantsStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
Admitted into intensive care unit7575
Not admitted to intensive care525531
SecondaryDeath From Any Cause

Number of participants who died from any cause

Time frame:
Up to date of death or day 4 from admission
Reported as:
Count of participants · Participants
Death From Any Cause
ParticipantsStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
Number of Participants who lived611613
Number of Participants who died00
SecondaryBlood Pressure Measurements

Blood pressure at 15, 30, 45, 60, and 120 min after delivery

Time frame:
Up to 2 hours after the caesarean section
Reported as:
Mean · mmHg
Blood Pressure Measurements
mmHgStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
systolic blood pressure 15 minutes after delivery132.2 ± 17.6131.2 ± 18.0
diastolic blood pressure 15 minutes after delivery64.9 ± 33.869.1 ± 62.3
systolic blood pressure 30 minutes after delivery118.3 ± 17.3119.0 ± 16.5
diastolic blood pressure 30 minutes after delivery61.8 ± 14.565.5 ± 40.3
systolic blood pressure 45 minutes after delivery117.8 ± 18.9118.7 ± 18.3
diastolic blood pressure 45 minutes after delivery69.2 ± 11.768.2 ± 12.8
systolic blood pressure 60 minutes after delivery123.6 ± 18.1124.2 ± 16.2
SecondaryNumber of Mild Adverse Events

Number of mild events of nausea, vomiting, sensation of rings or spots of light in the visual field, dizziness

Time frame:
Up to 24 hours after administration
Reported as:
Count of participants · Participants
Number of Mild Adverse Events
ParticipantsStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
Nausea916
No Nausea602597
Vomiting2918
No Vomiting582595
Dizziness1214
No Dizziness599599
SecondaryNumber of Severe Adverse Events

* Deep vein thrombosis (if the diagnosis is confirmed by Doppler ultrasound) * Pulmonary embolism (if the diagnosis is confirmed by radiological examination) * Myocardial infarction * Seizure * Renal failure requiring dialysis

Time frame:
Up to day 3 postpartum
Reported as:
Count of participants · Participants
Number of Severe Adverse Events
ParticipantsStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
Deep Vein Thrombosis00
No Deep Vein Thrombosis611613
Pulmonary Embolism00
No Pulmonary Embolism611613
Myocardial Infarction01
No Myocardial Infarction611612
Seizures00
No Seizures611613
Renal failure requiring dialysis00
No Renal failure requiring dialysis611613
SecondaryAny Other Unexpected Adverse Event

Number of unexpected events during and after the adminstration of study drug and duration of observation

Time frame:
Up to day 3 postpartum
Reported as:
Count of participants · Participants
Any Other Unexpected Adverse Event
ParticipantsStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
Unexpected events00
No unexpected events611613
SecondaryLength of Hospital Stay

Duration of hospital admission in days

Time frame:
Up to day 3 postpartum
Reported as:
Mean · days
Length of Hospital Stay
daysStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
Length of Hospital Stay3.5 ± 1.13.5 ± 1.3

Adverse events

Collected over 1 week. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Study Group/Group A_(Tranexamic Acid)0/611 (0%)0/611 (0%)50/611 (8.2%)
Control Group/Group B_(Placebo)0/613 (0%)1/613 (0.2%)48/613 (7.8%)
Most frequent serious events
Most frequent serious events
EventStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
Myocardial InfarctionCardiac disorders0/6111/613
Most frequent other events
Most frequent other events
EventStudy Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)
VomitingGastrointestinal disorders29/61118/613
NauseaGastrointestinal disorders9/61116/613
DizzinessGeneral disorders12/61114/613

Baseline characteristics

Age, Continuous
Age, Continuous(years)Study Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)Total
Mean29.1 ± 6.228.3 ± 6.328.7 ± 6.3
Age, Customized
Age, Customized(Participants)Study Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)Total
Age Group — less than 18 years141630
Age Group — between 18-25 years168195363
Age Group — between 26-35 years322321643
Age Group — greater than 35 years10781188
Sex/Gender, Customized
Sex/Gender, Customized(Participants)Study Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)Total
Females6116131224
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)Study Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)Total
Count of participants——0
Weight (kg)
Weight (kg)(kg)Study Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)Total
Mean74.6 ± 16.273.5 ± 15.374.0 ± 15.8
Body Mass Index
Body Mass Index(kg/m^2)Study Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)Total
Mean29.5 ± 11.430.1 ± 19.629.8 ± 15.8
Abnormal Placentation
Abnormal Placentation(Participants)Study Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)Total
No abnormal placentation101
Abnormal placentation present6106131223
Anemia
Anemia(Participants)Study Group/Group A_(Tranexamic Acid)Control Group/Group B_(Placebo)Total
Anemia292049
Not anemic5825931175

10 further baseline measures are reported on the registry.

07

Study locations

2 sites
  • Parirenyatwa Group of Hospitals (Mbuya Nehanda Maternity Hospital)
    Harare, Zimbabwe
  • Sally Mugabe Central Hospital Maternity Unit
    Harare, Zimbabwe
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Jan 16, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — It is not yet known if there will be a plan to make individual patient data (IPD) available.

09

Registry details

Key details

Study ID
NCT04733157
Lead sponsor
University of Zimbabwe
Collaborators
Fogarty International Center of the National Institute of Health
Responsible party
Chipo Gwanzura, MD (Senior Registrar, University of Zimbabwe) — Principal investigator
First posted
Feb 1, 2021
Start date
Mar 23, 2021
Primary completion
Dec 14, 2021
Completion
Dec 14, 2021
Results posted
Mar 20, 2023
Last update
Mar 20, 2023

Study contacts

Chipo Gwanzura, MD
principal investigator · University of Zimbabwe

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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