Postpartum Hemorrhage, Uterine Atony
Conditions
Keywords
Uterine atony, Postpartum hemorrhage, clinical trial, Prophylactic oxytocin
Brief summary
This is a double-blind 3-arm randomized clinical trial to determine whether higher dose oxytocin regimens (compared to the standard regimen) reduce the frequency of uterine atony and postpartum hemorrhage after vaginal delivery. Uterine atony is a loss of tone in the uterine musculature which can cause acute postpartum hemorrhage, which is the major cause of maternal mortality worldwide. Oxytocin is routinely administered postpartum in the US and effectively reduces uterine atony. The optimal dose of oxytocin for vaginal delivery is not known.
Detailed description
Same as brief summary. Prospective interim monitoring (stopping) rules will be assessed upon recruitment of 2/3rds of the sample size of 1800. Interim review was conducted by a 3-member DSMB in January of 2010 and their recommendations were implemented.
Interventions
DRUGOxytocin
See arms
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* \> 24 weeks, viable pregnancy, singleton or twins
Exclusion criteria
* No consent * Contraindication to oxytocin * Antepartum fetal demise * Intrapartum use of concentrated oxytocin * Planned cesarean * DIC or coagulopathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Uterine Atony or Postpartum Hemorrhage Requiring Medical (Medication or Blood Transfusion), Surgical or Other Interventional Treatment | baseline to discharge (2 - 3 days) | the number of subjects with any treatment of uterineatony or hemorrhage. |
| Women in Each Group With Risk Factors for Atony or Postpartum Hemorrhage | Initial hospital discharge (2-3 days) | In a secondary data analysis, a parsimonious set of independent risk factors for atony or postpartum hemorrhage was established: White, Hispanic, or Other (non-Black of African American) race/ethnicity, preeclampsia, or chorioamnionitus. |
| Risk to Using Increasing Doses of Oxytocin Based on Pre-specified Risk Factors | baseline to discharge (2-3 days) | The frequency of the primary study outcome is examined in a subgroup of 939 women with risk factors for atony or postpartum hemorrhage. These risk factors are identified as White, Hispanic, or Other (non-Black or African American) race/ethnicity, chorioamnionitis, and preeclampsia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Hospital Stays Greater Than 4 Days | Initial hospital discharge (2 days or more) | Number of individuals with prolonged hospitalization defined as 4 days or more prior to initial hospital discharge |
| Change in Pre- to Post-delivery Hematocrit (%) | During delivery hospitalization: Admission hematocrit - post-delivery hematocrit | change in hematocrit from admission for delivery (baseline) to post-delivery (4 hours-1day postpartum depending on time of delivery) |
| Number of Subjects Requiring Hypotension Warranting Pressor Agent or Fluid Bolus | Initial hospital discharge (2-3 days or more) | number of individuals with hypotension leading to administration of a fluid bolus or vasopressor agent (medication given to raise the blood pressure) |
| Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | prior to discharge | the number of individuals with each of the component treatments or individual outcomes in the primary composite. |
| Number of Participants Experiencing Postpartum Hemorrhage (Clinical Estimate Greater Than 500cc) | Initial hospital discharge (2-3 days) | the number of individuals with a clinically estimated postpartum blood loss of 500cc or more |
Countries
United States
Participant flow
Recruitment details
There were 1,798 women randomized.
Pre-assignment details
At planned interim review (n=1,201), enrollment in the 40-unit group was stopped for futility and enrollment continued in the other groups.
Participants by arm
| Arm | Count |
|---|---|
| Oxytocin 10 Units/500cc | 659 |
| Oxytocin 40 Units/500cc Per DSMB recommendations, this intermediate arm was stopped Jan 2010. | 481 |
| Oxytocin 80U/500cc | 658 |
| Total | 1,798 |
Baseline characteristics
| Characteristic | Oxytocin 10 Units/500cc | Oxytocin 40 Units/500cc | Oxytocin 80U/500cc | Total |
|---|---|---|---|---|
| Age, Continuous Age (years) | 23.9 years STANDARD_DEVIATION 5.4 | 23.9 years STANDARD_DEVIATION 5.1 | 24.4 years STANDARD_DEVIATION 5.5 | 24.2 years STANDARD_DEVIATION 5.4 |
| Race/Ethnicity, Customized African American | 404 participants | 278 participants | 379 participants | 1061 participants |
| Race/Ethnicity, Customized Caucasian | 143 participants | 97 participants | 156 participants | 396 participants |
| Race/Ethnicity, Customized Hispanic | 106 participants | 101 participants | 120 participants | 327 participants |
| Race/Ethnicity, Customized Other (not specified) | 6 participants | 5 participants | 3 participants | 14 participants |
| Region of Enrollment United States | 659 participants | 481 participants | 658 participants | 1798 participants |
| Sex/Gender, Customized Female | 659 participants | 481 participants | 658 participants | 1798 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 659 | 0 / 481 | 0 / 658 |
| serious Total, serious adverse events | 0 / 659 | 0 / 481 | 0 / 658 |
Outcome results
Primary
Number of Subjects Reporting Uterine Atony or Postpartum Hemorrhage Requiring Medical (Medication or Blood Transfusion), Surgical or Other Interventional Treatment
the number of subjects with any treatment of uterineatony or hemorrhage.
Time frame: baseline to discharge (2 - 3 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxytocin 10 Units/500cc | Number of Subjects Reporting Uterine Atony or Postpartum Hemorrhage Requiring Medical (Medication or Blood Transfusion), Surgical or Other Interventional Treatment | 45 Participants |
| Oxytocin 40 Units/500cc | Number of Subjects Reporting Uterine Atony or Postpartum Hemorrhage Requiring Medical (Medication or Blood Transfusion), Surgical or Other Interventional Treatment | 31 Participants |
| Oxytocin 80U/500cc | Number of Subjects Reporting Uterine Atony or Postpartum Hemorrhage Requiring Medical (Medication or Blood Transfusion), Surgical or Other Interventional Treatment | 42 Participants |
Primary
Risk to Using Increasing Doses of Oxytocin Based on Pre-specified Risk Factors
The frequency of the primary study outcome is examined in a subgroup of 939 women with risk factors for atony or postpartum hemorrhage. These risk factors are identified as White, Hispanic, or Other (non-Black or African American) race/ethnicity, chorioamnionitis, and preeclampsia.
Time frame: baseline to discharge (2-3 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxytocin 10 Units/500cc | Risk to Using Increasing Doses of Oxytocin Based on Pre-specified Risk Factors | 37 participants |
| Oxytocin 40 Units/500cc | Risk to Using Increasing Doses of Oxytocin Based on Pre-specified Risk Factors | 22 participants |
| Oxytocin 80U/500cc | Risk to Using Increasing Doses of Oxytocin Based on Pre-specified Risk Factors | 28 participants |
p-value: 0.6795% CI: [0.63, 1.59]ANCOVA
Primary
Women in Each Group With Risk Factors for Atony or Postpartum Hemorrhage
In a secondary data analysis, a parsimonious set of independent risk factors for atony or postpartum hemorrhage was established: White, Hispanic, or Other (non-Black of African American) race/ethnicity, preeclampsia, or chorioamnionitus.
Time frame: Initial hospital discharge (2-3 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxytocin 10 Units/500cc | Women in Each Group With Risk Factors for Atony or Postpartum Hemorrhage | 351 participants |
| Oxytocin 40 Units/500cc | Women in Each Group With Risk Factors for Atony or Postpartum Hemorrhage | 255 participants |
| Oxytocin 80U/500cc | Women in Each Group With Risk Factors for Atony or Postpartum Hemorrhage | 333 participants |
Secondary
Change in Pre- to Post-delivery Hematocrit (%)
change in hematocrit from admission for delivery (baseline) to post-delivery (4 hours-1day postpartum depending on time of delivery)
Time frame: During delivery hospitalization: Admission hematocrit - post-delivery hematocrit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oxytocin 10 Units/500cc | Change in Pre- to Post-delivery Hematocrit (%) | 4 hematocrit difference (%) |
| Oxytocin 40 Units/500cc | Change in Pre- to Post-delivery Hematocrit (%) | 4 hematocrit difference (%) |
| Oxytocin 80U/500cc | Change in Pre- to Post-delivery Hematocrit (%) | 4 hematocrit difference (%) |
Secondary
Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome
the number of individuals with each of the component treatments or individual outcomes in the primary composite.
Time frame: prior to discharge
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oxytocin 10 Units/500cc | Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | Other-Tamponade | 0 Participants |
| Oxytocin 10 Units/500cc | Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | Surgical | 0 Participants |
| Oxytocin 10 Units/500cc | Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | Any Uterotonic | 45 Participants |
| Oxytocin 10 Units/500cc | Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | Blood Transfusion | 7 Participants |
| Oxytocin 10 Units/500cc | Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | Other-Arterial embolization | 1 Participants |
| Oxytocin 40 Units/500cc | Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | Surgical | 0 Participants |
| Oxytocin 40 Units/500cc | Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | Any Uterotonic | 30 Participants |
| Oxytocin 40 Units/500cc | Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | Blood Transfusion | 4 Participants |
| Oxytocin 40 Units/500cc | Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | Other-Tamponade | 1 Participants |
| Oxytocin 40 Units/500cc | Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | Other-Arterial embolization | 0 Participants |
| Oxytocin 80U/500cc | Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | Other-Arterial embolization | 1 Participants |
| Oxytocin 80U/500cc | Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | Other-Tamponade | 0 Participants |
| Oxytocin 80U/500cc | Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | Any Uterotonic | 40 Participants |
| Oxytocin 80U/500cc | Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | Surgical | 1 Participants |
| Oxytocin 80U/500cc | Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | Blood Transfusion | 5 Participants |
Secondary
Number of Participants Experiencing Postpartum Hemorrhage (Clinical Estimate Greater Than 500cc)
the number of individuals with a clinically estimated postpartum blood loss of 500cc or more
Time frame: Initial hospital discharge (2-3 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxytocin 10 Units/500cc | Number of Participants Experiencing Postpartum Hemorrhage (Clinical Estimate Greater Than 500cc) | 38 Participants |
| Oxytocin 40 Units/500cc | Number of Participants Experiencing Postpartum Hemorrhage (Clinical Estimate Greater Than 500cc) | 24 Participants |
| Oxytocin 80U/500cc | Number of Participants Experiencing Postpartum Hemorrhage (Clinical Estimate Greater Than 500cc) | 24 Participants |
Secondary
Number of Subjects Requiring Hypotension Warranting Pressor Agent or Fluid Bolus
number of individuals with hypotension leading to administration of a fluid bolus or vasopressor agent (medication given to raise the blood pressure)
Time frame: Initial hospital discharge (2-3 days or more)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oxytocin 10 Units/500cc | Number of Subjects Requiring Hypotension Warranting Pressor Agent or Fluid Bolus | Pressor agent (medication given to increase BP) | 85 Participants |
| Oxytocin 10 Units/500cc | Number of Subjects Requiring Hypotension Warranting Pressor Agent or Fluid Bolus | Fluid bolus | 82 Participants |
| Oxytocin 40 Units/500cc | Number of Subjects Requiring Hypotension Warranting Pressor Agent or Fluid Bolus | Pressor agent (medication given to increase BP) | 56 Participants |
| Oxytocin 40 Units/500cc | Number of Subjects Requiring Hypotension Warranting Pressor Agent or Fluid Bolus | Fluid bolus | 51 Participants |
| Oxytocin 80U/500cc | Number of Subjects Requiring Hypotension Warranting Pressor Agent or Fluid Bolus | Pressor agent (medication given to increase BP) | 95 Participants |
| Oxytocin 80U/500cc | Number of Subjects Requiring Hypotension Warranting Pressor Agent or Fluid Bolus | Fluid bolus | 87 Participants |
Secondary
Number of Subjects With Hospital Stays Greater Than 4 Days
Number of individuals with prolonged hospitalization defined as 4 days or more prior to initial hospital discharge
Time frame: Initial hospital discharge (2 days or more)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxytocin 10 Units/500cc | Number of Subjects With Hospital Stays Greater Than 4 Days | 116 Participants |
| Oxytocin 40 Units/500cc | Number of Subjects With Hospital Stays Greater Than 4 Days | 95 Participants |
| Oxytocin 80U/500cc | Number of Subjects With Hospital Stays Greater Than 4 Days | 109 Participants |