Hemorrhage
Conditions
Brief summary
Excessive bleeding after dilation and evacuation (D&E) requiring interventions is common, occurring in approximately 30% of cases at one large abortion-providing clinic. Uterotonic prophylaxis at the time of D&E, particularly with methylergonovine maleate (MM), is a common practice among D&E providers despite nearly no evidence for its efficacy. Finding ways to decrease excessive bleeding after D&E has the potential both to improve patient safety and to reduce costs of provider-initiated interventions. The investigators propose a randomized, controlled trial to investigate the efficacy of MM prophylaxis versus placebo in decreasing excessive bleeding measured by a composite outcome among women undergoing D&E at 20 to 24 weeks.
Interventions
DRUGMethergine
0.2 mg of methylergonovine maleate
OTHERplacebo
saline placebo to maintain blinding
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Between 20 wks 0 days gestation and 24 wks 0 days gestation * English or Spanish speaking * BP before injection 140/90 or below * 18 years old or over
Exclusion criteria
* hypertension either on the preoperative or operative day (defined as systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg) * D&E procedures with more than one day of cervical preparation with dilators * use of protease inhibitors * known coagulopathy * known morbidly adherent placenta
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Given Any Uterotonic | intra-operative or post-operative until discharge | any uterotonic medication given intraoperative or postoperative |
| Number of Participants Who Had a Balloon Tamponade Placed From Start of Procedure to Hospital Discharge | duration of procedure and until discharged from hospital | number of participants who had a balloon tamponade placed |
| Number of Participants Who Returned to OR for Re-aspiration During Recovery Period | from cervical preparation through discharge | Returned to OR for re-aspiration |
| Number of Participants Who Were Admitted for Bleeding After Procedure | post-procedure and during recovery until discharge | hospital admission for bleeding post-procedure |
| Number of Participants With Excessive Bleeding as Determined by the Composite Outcome Criteria | Approximately 1-2 hours after procedure | Clinical factors included in composite outcome of excessive bleeding after D&E: Post-procedure total blood loss \> 125cc (after D&E) Transfusion Admission for bleeding Re-aspiration for bleeding Balloon tamponade Uterine artery embolization Major surgery for bleeding At least 1 uterotonic medication given Prescription given for any uterotonic medication at discharge Uterine compression (uterine massage or manual pressure for 2 minutes |
| Amount of Post-procedure Blood Loss Measured in mL | measured 1 to 2 hours after procedure | post-procedure blood loss measured in recovery room |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Reported Vomiting up to One Hour After Procedure | Assessed approximately 1 hour after procedure | Patients' completed survey regarding side effects in recovery room. |
| Number of Participants Who Reported Cramping up to One Hour After Procedure | Assessed approximately 1 hour after procedure | Patients' completed survey regarding side effects in recovery room. |
| Number of Participants Who Reported Nausea up to One Hour After Procedure | Assessed approximately 1 hour after procedure | Patients' completed survey regarding side effects in recovery room. |
Countries
United States
Participant flow
Pre-assignment details
Determined ineligible (n=28) Patient withdrew (n=6) Administrative error (n=2)
Participants by arm
| Arm | Count |
|---|---|
| Methergine Methergine group | 140 |
| Placebo Placebo group | 144 |
| Total | 284 |
Baseline characteristics
| Characteristic | Methergine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 24.5 years | 25 years | 24.8 years |
| Body mass index | 26.5 kg/m2 | 26 kg/m2 | 26.3 kg/m2 |
| Current or recent cocaine or methamphetamine use | 11 Participants | 19 Participants | 30 Participants |
| Gestation | 21.6 weeks | 21.5 weeks | 21.6 weeks |
| History of bleeding disorder | 2 Participants | 3 Participants | 5 Participants |
| Length of procedure | 12 minutes | 12 minutes | 12 minutes |
| Needed mechanical dilation | 7 Participants | 5 Participants | 12 Participants |
| Nulliparous | 35 Participants | 37 Participants | 72 Participants |
| Preoperative diastolic BP | 68 mmHg STANDARD_DEVIATION 9 | 69 mmHg STANDARD_DEVIATION 8 | 69 mmHg STANDARD_DEVIATION 8 |
| Preoperative systolic BP | 112 mmHg STANDARD_DEVIATION 11 | 112 mmHg STANDARD_DEVIATION 10 | 112 mmHg STANDARD_DEVIATION 10 |
| Prior cesarean section | 24 Participants | 27 Participants | 51 Participants |
| Procedural measured blood loss | 300 mL | 250 mL | 275 mL |
| Race/Ethnicity, Customized Asian | 7 Participants | 7 Participants | 14 Participants |
| Race/Ethnicity, Customized Hispanic | 37 Participants | 33 Participants | 70 Participants |
| Race/Ethnicity, Customized Mixed | 19 Participants | 15 Participants | 34 Participants |
| Race/Ethnicity, Customized Non-Hispanic black | 26 Participants | 33 Participants | 59 Participants |
| Race/Ethnicity, Customized Non-Hispanic white | 39 Participants | 48 Participants | 87 Participants |
| Race/Ethnicity, Customized Other | 11 Participants | 8 Participants | 19 Participants |
| Sex: Female, Male Female | 140 Participants | 144 Participants | 284 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 140 | 0 / 144 |
| other Total, other adverse events | 20 / 140 | 11 / 144 |
| serious Total, serious adverse events | 4 / 140 | 0 / 144 |
Outcome results
Primary
Amount of Post-procedure Blood Loss Measured in mL
post-procedure blood loss measured in recovery room
Time frame: measured 1 to 2 hours after procedure
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Methergine | Amount of Post-procedure Blood Loss Measured in mL | 126 mL |
| Placebo | Amount of Post-procedure Blood Loss Measured in mL | 76 mL |
p-value: 0.02t-test, 2 sided
Primary
Number of Participants Given Any Uterotonic
any uterotonic medication given intraoperative or postoperative
Time frame: intra-operative or post-operative until discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methergine | Number of Participants Given Any Uterotonic | 56 Participants |
| Placebo | Number of Participants Given Any Uterotonic | 43 Participants |
p-value: 0.07Chi-squared
Primary
Number of Participants Who Had a Balloon Tamponade Placed From Start of Procedure to Hospital Discharge
number of participants who had a balloon tamponade placed
Time frame: duration of procedure and until discharged from hospital
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methergine | Number of Participants Who Had a Balloon Tamponade Placed From Start of Procedure to Hospital Discharge | 20 Participants |
| Placebo | Number of Participants Who Had a Balloon Tamponade Placed From Start of Procedure to Hospital Discharge | 10 Participants |
p-value: 0.04Chi-squared
Primary
Number of Participants Who Returned to OR for Re-aspiration During Recovery Period
Returned to OR for re-aspiration
Time frame: from cervical preparation through discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methergine | Number of Participants Who Returned to OR for Re-aspiration During Recovery Period | 4 Participants |
| Placebo | Number of Participants Who Returned to OR for Re-aspiration During Recovery Period | 0 Participants |
p-value: 0.06Chi-squared
Primary
Number of Participants Who Were Admitted for Bleeding After Procedure
hospital admission for bleeding post-procedure
Time frame: post-procedure and during recovery until discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methergine | Number of Participants Who Were Admitted for Bleeding After Procedure | 4 Participants |
| Placebo | Number of Participants Who Were Admitted for Bleeding After Procedure | 0 Participants |
p-value: 0.06Chi-squared
Primary
Number of Participants With Excessive Bleeding as Determined by the Composite Outcome Criteria
Clinical factors included in composite outcome of excessive bleeding after D&E: Post-procedure total blood loss \> 125cc (after D&E) Transfusion Admission for bleeding Re-aspiration for bleeding Balloon tamponade Uterine artery embolization Major surgery for bleeding At least 1 uterotonic medication given Prescription given for any uterotonic medication at discharge Uterine compression (uterine massage or manual pressure for 2 minutes
Time frame: Approximately 1-2 hours after procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methergine | Number of Participants With Excessive Bleeding as Determined by the Composite Outcome Criteria | 78 Participants |
| Placebo | Number of Participants With Excessive Bleeding as Determined by the Composite Outcome Criteria | 75 Participants |
p-value: 0.5Chi-squared
Secondary
Number of Participants Who Reported Cramping up to One Hour After Procedure
Patients' completed survey regarding side effects in recovery room.
Time frame: Assessed approximately 1 hour after procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methergine | Number of Participants Who Reported Cramping up to One Hour After Procedure | 100 Participants |
| Placebo | Number of Participants Who Reported Cramping up to One Hour After Procedure | 84 Participants |
p-value: 0.02Chi-squared
Secondary
Number of Participants Who Reported Nausea up to One Hour After Procedure
Patients' completed survey regarding side effects in recovery room.
Time frame: Assessed approximately 1 hour after procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methergine | Number of Participants Who Reported Nausea up to One Hour After Procedure | 42 Participants |
| Placebo | Number of Participants Who Reported Nausea up to One Hour After Procedure | 18 Participants |
p-value: <0.001Chi-squared
Secondary
Number of Patients Who Reported Vomiting up to One Hour After Procedure
Patients' completed survey regarding side effects in recovery room.
Time frame: Assessed approximately 1 hour after procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methergine | Number of Patients Who Reported Vomiting up to One Hour After Procedure | 18 Participants |
| Placebo | Number of Patients Who Reported Vomiting up to One Hour After Procedure | 8 Participants |
p-value: 0.03Chi-squared