Intrauterine Fetal Demise
Conditions
Keywords
intrauterine fetal death, misoprostol
Brief summary
The purpose of the proposed study is to test - in a randomized, blinded trial - two different doses of the prostaglandin E1 analogue misoprostol administered buccally as a treatment for fetal death at 14 - 28 weeks, inclusive, of pregnancy. At such an advanced stage of pregnancy, the nonviable fetus is often not spontaneously evacuated, and yet timely evacuation is vital in order to avoid the possibility of, among other things, potentially life-threatening maternal coagulopathies. Current approaches to uterine evacuation in these cases include dilatation and evacuation (D&E) surgery (in less advanced pregnancies) and labor induction with a variety of products. Misoprostol has been demonstrated to be as effective as, or more effective than, either oxytocin or prostaglandin E2 analogues for this indication in a number of small, non-FDA-approved trials which have been published in the peer-reviewed literature. In the absence of more formal study of this treatment, however, dosages are not standardized, pathways of administration vary, and other uncertainties linger. The purpose of the protocol proposed herein is to formally establish, via a randomized, double-blinded study, the safety and effectiveness of misoprostol for this indication, and to compare the value of two distinct doses, so that providers may henceforward proceed with greater authority and confidence.
Interventions
DRUGMisoprostol
200 mcg buccal misoprostol administered every 6 hours for up to 48 hours until fetus is delivered.
Sponsors
Stanford University
Albert Einstein College of Medicine
University of Florida
Huong Vuong Hospital
Boston Medical Center
Christiana Care Health Services
University of Illinois at Chicago
Gynuity Health Projects
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Women presents with spontaneous fetal death * Gestational age of fetus between 14-28 weeks
Exclusion criteria
* Transmural uterine scar; * Allergies or other contraindications to use of misoprostol; * Placental abruption with active hemorrhage; * Complete placenta previa; * Extreme uterine structural anomalies; * Or other contraindications to vaginal delivery of the fetus; * Presentation in active labor (moderate to severe contractions every 10 minutes); or * Four or more previous deliveries
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Successful Expulsion of Fetus and Placenta Within 48 Hours | 48 hours |
Countries
United States, Vietnam
Participant flow
Recruitment details
This randomized trial was conducted at Montefiore Medical Center, Stanford University, Stroger Hospital, Christiana Care Hospital, the Huong Vuong Hospital in Ho Chi Minh City, Viet Nam. Women who sought medical care for possible fetal demise in pregnancies of between 14 and 28 weeks from December 2008 to December 2011 were screened.
Pre-assignment details
No participants were excluded from the trial before assignment to groups.
Participants by arm
| Arm | Count |
|---|---|
| 200 Mcg Women in Group 1 will be administered two tablets (2 100 mcg misoprostol tablets), which she will be instructed to hold in her cheeks for 200 minutes, after which she will swallow any medication that remains. In cases where cervical dilation is not complete after six hours, women will be given a second dose of study drug. Study drug will continue to be administered at 6-hourly intervals through hour 42 after the study dose. | 77 |
| 100 Mcg Women in Group 1 will be administered two tablets (a 100 mcg misoprostol tablet and a placebo tablet made to resemble a 100 mcg misoprostol tablet), which she will be instructed to hold in her cheeks for 200 minutes, after which she will swallow any medication that remains. In cases where cervical dilation is not complete after six hours, women will be given a second dose of study drug. Study drug will continue to be administered at 6-hourly intervals through hour 42 after the study dose. | 76 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | 200 Mcg | 100 Mcg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 4 Participants | 3 Participants | 7 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 73 Participants | 73 Participants | 146 Participants |
| Age Continuous | 25.6 years STANDARD_DEVIATION 5.6 | 25.8 years STANDARD_DEVIATION 5.9 | 25.7 years STANDARD_DEVIATION 5.7 |
| Region of Enrollment United States | 7 participants | 6 participants | 13 participants |
| Region of Enrollment Vietnam | 70 participants | 70 participants | 140 participants |
| Sex: Female, Male Female | 77 Participants | 76 Participants | 153 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 | — / — | — / — |
| other Total, other adverse events | 1 / 77 | 0 / 76 |
| serious Total, serious adverse events | 0 / 77 | 0 / 76 |
Outcome results
Primary
Successful Expulsion of Fetus and Placenta Within 48 Hours
Time frame: 48 hours
Population: One woman assigned to the 200μg arm was determined to be ineligible after enrollment due to a gestational age less than 14 weeks. She was not included in the analysis. One woman in the 100mcg arm was withdrawn from the study due to preeclampsia. She was included in the analysis as a failed induction.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 200 Mcg | Successful Expulsion of Fetus and Placenta Within 48 Hours | 60 participants |
| 100 Mcg | Successful Expulsion of Fetus and Placenta Within 48 Hours | 47 participants |
Comparison: Rates of success were compared across study arms. The study was a separate, non-comparative efficacy study. In order to have 80% power (alpha=.05) to demonstrate that each misoprostol regimen was 95%, ± 5%, effective, we enrolled 73 women in each arm of the study, or 146 women total. The sample size also provided 80% power (alpha=.05) to detect a significant difference between treatments should 200μg prove 98% effective and 100μg prove 88% effective.p-value: <0.05Chi-squared