Trial Outcomes & Findings for Fetal and Infant Effects of Maternal Buprenorphine Treatment (NCT NCT01561079)
NCT ID: NCT01561079
Last Updated: 2017-09-26
Results Overview
Fetal heart rate in beats per minute at time of trough and peak maternal buprenorphine levels
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
127 participants
Primary outcome timeframe
24, 28, 32 and 36 weeks of gestation
Results posted on
2017-09-26
Participant Flow
Participants were recruited from a comprehensive care treatment facility for pregnant and postpartum women with substance use disorders between Feb 2012 and March 2016
Participants must have an opioid use disorder, a singleton, generally uncomplicated pregnancy, be between 18 and 40 years of age, have accurate gestational age dating of less than 34 weeks, willing to receive obstetric care at the center and deliver their infant at the hospital affiliated with the treatment facility.
Participant milestones
| Measure |
Maternal Buprenorphine Treatment
Daily sublingual buprenorphine treatment of pregnant, opioid dependent women Subjects undergo maternal-fetal monitoring at any combination of the following gestational time periods: 24, 28,32, 36 weeks of gestation
|
|---|---|
|
Overall Study
STARTED
|
127
|
|
Overall Study
COMPLETED
|
49
|
|
Overall Study
NOT COMPLETED
|
78
|
Reasons for withdrawal
| Measure |
Maternal Buprenorphine Treatment
Daily sublingual buprenorphine treatment of pregnant, opioid dependent women Subjects undergo maternal-fetal monitoring at any combination of the following gestational time periods: 24, 28,32, 36 weeks of gestation
|
|---|---|
|
Overall Study
Physician Decision
|
17
|
|
Overall Study
Withdrawal by Subject
|
59
|
|
Overall Study
Protocol Violation
|
2
|
Baseline Characteristics
Fetal and Infant Effects of Maternal Buprenorphine Treatment
Baseline characteristics by cohort
| Measure |
Fetal
n=49 Participants
Daily sublingual buprenorphine treatment of pregnant, opioid dependent women Subjects completing any maternal-fetal monitoring at any combination of the following gestational ages: 24, 28, 32 36 weeks
|
|---|---|
|
Age, Continuous
|
27.6 years
STANDARD_DEVIATION 4.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
49 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
43 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Education
|
11.5 years
STANDARD_DEVIATION 1.9 • n=5 Participants
|
|
Age at first substance use
|
19.8 years
STANDARD_DEVIATION 4.8 • n=5 Participants
|
|
Age at regular substance use
|
21.0 years
STANDARD_DEVIATION 4.6 • n=5 Participants
|
|
Duration of regular substance use upon treatment entry
|
6.5 years
STANDARD_DEVIATION 4.4 • n=5 Participants
|
|
Gestational age upon treatment entry
|
21.3 weeks
STANDARD_DEVIATION 7.0 • n=5 Participants
|
|
Length of time in treatment prior to delivery
|
121.1 days
STANDARD_DEVIATION 56.7 • n=5 Participants
|
|
Buprenorphine dose at 24 weeks if gestation
|
12.0 mg
STANDARD_DEVIATION 7.1 • n=5 Participants
|
|
Buprenorphine dose at 28 weeks if gestation
|
12.3 mg
STANDARD_DEVIATION 6.0 • n=5 Participants
|
|
Buprenorphine dose at 32 weeks if gestation
|
12.7 mg
STANDARD_DEVIATION 6.3 • n=5 Participants
|
|
Buprenorphine dose at 36 weeks if gestation
|
12.8 mg
STANDARD_DEVIATION 6.5 • n=5 Participants
|
|
Urine toxicology screenings during treatment
|
16.4 number of screenings
STANDARD_DEVIATION 8.0 • n=5 Participants
|
|
Positive research urine toxicology screening at delivery
|
19.7 percent positive urine tox. screenings
STANDARD_DEVIATION 25.6 • n=5 Participants
|
PRIMARY outcome
Timeframe: 24, 28, 32 and 36 weeks of gestationPopulation: Participants active in the protocol at 24, 28, 32 and 36 weeks, respectively
Fetal heart rate in beats per minute at time of trough and peak maternal buprenorphine levels
Outcome measures
| Measure |
FHR 24 Weeks Trough
n=20 Participants
Fetal heart rate in beats per minute at 24 weeks of gestation at trough
|
FHR 28 Weeks Trough
n=30 Participants
Fetal heart rate in beats per minute at 28 weeks of gestation at time of trough maternal buprenorphine level
|
FHR 32 Weeks Trough
n=42 Participants
Fetal heart rate in beats per minute at 32 weeks of gestation at time of trough maternal buprenorphine level
|
FHR 36 Weeks Trough
n=40 Participants
Fetal heart rate in beats per minute at 36 weeks of gestation at time of trough maternal buprenorphine level
|
FHR 24 Weeks Peak
n=20 Participants
Fetal heart rate in beats per minute at 24 weeks of gestation at time of peak maternal buprenorphine level
|
FHR 28 Weeks Peak
n=30 Participants
Fetal heart rate in beats per minute at 28 weeks of gestation at time of peak maternal buprenorphine level
|
FHR 32 Peak
n=42 Participants
Fetal heart rate in beats per minute at 32 weeks of gestation at time of peak maternal buprenorphine level
|
FHR 36 Peak
n=40 Participants
Fetal heart rate in beats per minute at 36 weeks of gestation at time of peak maternal buprenorphine level
|
|---|---|---|---|---|---|---|---|---|
|
Fetal Heart Rate
|
145.7 beats per minute
Standard Deviation 5.8
|
143.3 beats per minute
Standard Deviation 5.4
|
138.6 beats per minute
Standard Deviation 6.0
|
136.3 beats per minute
Standard Deviation 7.1
|
143.9 beats per minute
Standard Deviation 6.4
|
141.0 beats per minute
Standard Deviation 4.8
|
135.4 beats per minute
Standard Deviation 6.3
|
131.3 beats per minute
Standard Deviation 6.1
|
PRIMARY outcome
Timeframe: 24, 28, 32 and 36 weeks of gestationPopulation: Per protocol
Fetal heart rate variability at 24, 28, 32 and 36 weeks of gestation at times of trough and peak maternal buprenorphine levels
Outcome measures
| Measure |
FHR 24 Weeks Trough
n=20 Participants
Fetal heart rate in beats per minute at 24 weeks of gestation at trough
|
FHR 28 Weeks Trough
n=30 Participants
Fetal heart rate in beats per minute at 28 weeks of gestation at time of trough maternal buprenorphine level
|
FHR 32 Weeks Trough
n=42 Participants
Fetal heart rate in beats per minute at 32 weeks of gestation at time of trough maternal buprenorphine level
|
FHR 36 Weeks Trough
n=40 Participants
Fetal heart rate in beats per minute at 36 weeks of gestation at time of trough maternal buprenorphine level
|
FHR 24 Weeks Peak
n=20 Participants
Fetal heart rate in beats per minute at 24 weeks of gestation at time of peak maternal buprenorphine level
|
FHR 28 Weeks Peak
n=30 Participants
Fetal heart rate in beats per minute at 28 weeks of gestation at time of peak maternal buprenorphine level
|
FHR 32 Peak
n=42 Participants
Fetal heart rate in beats per minute at 32 weeks of gestation at time of peak maternal buprenorphine level
|
FHR 36 Peak
n=40 Participants
Fetal heart rate in beats per minute at 36 weeks of gestation at time of peak maternal buprenorphine level
|
|---|---|---|---|---|---|---|---|---|
|
Fetal Heart Rate Variability
|
5.4 msec
Standard Deviation 1.3
|
6.7 msec
Standard Deviation 1.9
|
7.5 msec
Standard Deviation 3.0
|
7.9 msec
Standard Deviation 2.1
|
4.9 msec
Standard Deviation 1.5
|
7.3 msec
Standard Deviation 1.8
|
7.0 msec
Standard Deviation 2.7
|
6.3 msec
Standard Deviation 2.1
|
PRIMARY outcome
Timeframe: 24, 28, 32 36 weeks of gestationNumber of accelerations of fetal heart rate exhibited during the 60 minute recordings
Outcome measures
| Measure |
FHR 24 Weeks Trough
n=20 Participants
Fetal heart rate in beats per minute at 24 weeks of gestation at trough
|
FHR 28 Weeks Trough
n=30 Participants
Fetal heart rate in beats per minute at 28 weeks of gestation at time of trough maternal buprenorphine level
|
FHR 32 Weeks Trough
n=42 Participants
Fetal heart rate in beats per minute at 32 weeks of gestation at time of trough maternal buprenorphine level
|
FHR 36 Weeks Trough
n=40 Participants
Fetal heart rate in beats per minute at 36 weeks of gestation at time of trough maternal buprenorphine level
|
FHR 24 Weeks Peak
n=20 Participants
Fetal heart rate in beats per minute at 24 weeks of gestation at time of peak maternal buprenorphine level
|
FHR 28 Weeks Peak
n=30 Participants
Fetal heart rate in beats per minute at 28 weeks of gestation at time of peak maternal buprenorphine level
|
FHR 32 Peak
n=42 Participants
Fetal heart rate in beats per minute at 32 weeks of gestation at time of peak maternal buprenorphine level
|
FHR 36 Peak
n=40 Participants
Fetal heart rate in beats per minute at 36 weeks of gestation at time of peak maternal buprenorphine level
|
|---|---|---|---|---|---|---|---|---|
|
Accelerations of Fetal Heart Rate
|
0.52 accelerations
Interval 0.0 to 3.0
|
1.59 accelerations
Interval 0.0 to 8.0
|
3.57 accelerations
Interval 0.0 to 15.0
|
5.28 accelerations
Interval 0.0 to 17.0
|
0.43 accelerations
Interval 0.0 to 3.0
|
2.12 accelerations
Interval 0.0 to 7.0
|
2.29 accelerations
Interval 0.0 to 9.0
|
2.25 accelerations
Interval 0.0 to 9.0
|
PRIMARY outcome
Timeframe: 24, 28, 32, 36 weeks of gestationFetal movement (number x duration of fetal movements) during the 60 minute recordings at times of trough and peak maternal buprenorphine levels
Outcome measures
| Measure |
FHR 24 Weeks Trough
n=20 Participants
Fetal heart rate in beats per minute at 24 weeks of gestation at trough
|
FHR 28 Weeks Trough
n=30 Participants
Fetal heart rate in beats per minute at 28 weeks of gestation at time of trough maternal buprenorphine level
|
FHR 32 Weeks Trough
n=42 Participants
Fetal heart rate in beats per minute at 32 weeks of gestation at time of trough maternal buprenorphine level
|
FHR 36 Weeks Trough
n=40 Participants
Fetal heart rate in beats per minute at 36 weeks of gestation at time of trough maternal buprenorphine level
|
FHR 24 Weeks Peak
n=20 Participants
Fetal heart rate in beats per minute at 24 weeks of gestation at time of peak maternal buprenorphine level
|
FHR 28 Weeks Peak
n=30 Participants
Fetal heart rate in beats per minute at 28 weeks of gestation at time of peak maternal buprenorphine level
|
FHR 32 Peak
n=42 Participants
Fetal heart rate in beats per minute at 32 weeks of gestation at time of peak maternal buprenorphine level
|
FHR 36 Peak
n=40 Participants
Fetal heart rate in beats per minute at 36 weeks of gestation at time of peak maternal buprenorphine level
|
|---|---|---|---|---|---|---|---|---|
|
Fetal Movement
|
1496.2 seconds
Standard Deviation 752.0
|
1390.0 seconds
Standard Deviation 795.4
|
1458.7 seconds
Standard Deviation 674.6
|
1446.7 seconds
Standard Deviation 979.5
|
1613.0 seconds
Standard Deviation 575.6
|
1385.7 seconds
Standard Deviation 674.5
|
1381.2 seconds
Standard Deviation 830.7
|
1038.2 seconds
Standard Deviation 756.2
|
PRIMARY outcome
Timeframe: 24, 28, 32, 36 weeks of gestationThe integration between fetal movements and heart rate (FM-FHR coupling) was quantified as the proportion of time individual movements were associated with a change in FHR, using previously developed criteria. FM-FHR coupling reflects coactivation of the sympathetic and parasympathetic components of the autonomic nervous system.
Outcome measures
| Measure |
FHR 24 Weeks Trough
n=20 Participants
Fetal heart rate in beats per minute at 24 weeks of gestation at trough
|
FHR 28 Weeks Trough
n=30 Participants
Fetal heart rate in beats per minute at 28 weeks of gestation at time of trough maternal buprenorphine level
|
FHR 32 Weeks Trough
n=42 Participants
Fetal heart rate in beats per minute at 32 weeks of gestation at time of trough maternal buprenorphine level
|
FHR 36 Weeks Trough
n=40 Participants
Fetal heart rate in beats per minute at 36 weeks of gestation at time of trough maternal buprenorphine level
|
FHR 24 Weeks Peak
n=20 Participants
Fetal heart rate in beats per minute at 24 weeks of gestation at time of peak maternal buprenorphine level
|
FHR 28 Weeks Peak
n=30 Participants
Fetal heart rate in beats per minute at 28 weeks of gestation at time of peak maternal buprenorphine level
|
FHR 32 Peak
n=42 Participants
Fetal heart rate in beats per minute at 32 weeks of gestation at time of peak maternal buprenorphine level
|
FHR 36 Peak
n=40 Participants
Fetal heart rate in beats per minute at 36 weeks of gestation at time of peak maternal buprenorphine level
|
|---|---|---|---|---|---|---|---|---|
|
Fetal Movement - Fetal Heart Rate Coupling
|
0.13 percentage of time FM assoc w FHR change
Standard Deviation 0.06
|
0.21 percentage of time FM assoc w FHR change
Standard Deviation .07
|
0.23 percentage of time FM assoc w FHR change
Standard Deviation 0.10
|
0.25 percentage of time FM assoc w FHR change
Standard Deviation 0.11
|
0.09 percentage of time FM assoc w FHR change
Standard Deviation 0.06
|
0.20 percentage of time FM assoc w FHR change
Standard Deviation 0.09
|
0.21 percentage of time FM assoc w FHR change
Standard Deviation 0.10
|
0.20 percentage of time FM assoc w FHR change
Standard Deviation 0.10
|
Adverse Events
Maternal Buprenorphine Treatment
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Maternal Buprenorphine Treatment
n=49 participants at risk
Buprenorphine maintenance during pregnancy
Buprenorphine: Daily sublingual buprenorphine treatment of pregnant, opioid dependent women from up to 34 weeks gestation through one month of infant age.
Two severe adverse events were reported in the same infant patient. One infant had congenital heart disease and polydactyly
|
|---|---|
|
Congenital, familial and genetic disorders
Severe adverse event
|
2.0%
1/49 • Number of events 1 • 3 years, 3 months
|
|
Cardiac disorders
congenital heart disease
|
2.0%
1/49 • Number of events 1 • 3 years, 3 months
|
Other adverse events
| Measure |
Maternal Buprenorphine Treatment
n=49 participants at risk
Buprenorphine maintenance during pregnancy
Buprenorphine: Daily sublingual buprenorphine treatment of pregnant, opioid dependent women from up to 34 weeks gestation through one month of infant age.
Two severe adverse events were reported in the same infant patient. One infant had congenital heart disease and polydactyly
|
|---|---|
|
Hepatobiliary disorders
Cholestasis of pregnancy
|
6.1%
3/49 • Number of events 3 • 3 years, 3 months
|
|
Infections and infestations
Bacterial vaginosis
|
2.0%
1/49 • Number of events 1 • 3 years, 3 months
|
|
Nervous system disorders
choroid plexus cysts
|
2.0%
1/49 • Number of events 1 • 3 years, 3 months
|
|
Cardiac disorders
cardiomegaly
|
4.1%
2/49 • Number of events 2 • 3 years, 3 months
|
|
Infections and infestations
pneumonia
|
2.0%
1/49 • Number of events 1 • 3 years, 3 months
|
|
General disorders
fetal growth restriction
|
2.0%
1/49 • Number of events 1 • 3 years, 3 months
|
|
Pregnancy, puerperium and perinatal conditions
chorioamnionitis
|
4.1%
2/49 • Number of events 2 • 3 years, 3 months
|
|
Pregnancy, puerperium and perinatal conditions
Fetal stress at delivery
|
4.1%
2/49 • Number of events 2 • 3 years, 3 months
|
|
General disorders
psychiatric concern
|
2.0%
1/49 • Number of events 1 • 3 years, 3 months
|
|
Cardiac disorders
fetal arrythmia
|
2.0%
1/49 • Number of events 1 • 3 years, 3 months
|
|
General disorders
maternal dehydration
|
2.0%
1/49 • Number of events 1 • 3 years, 3 months
|
|
Pregnancy, puerperium and perinatal conditions
nonreactive fetal tracing, fetal hear rate deceleration
|
4.1%
2/49 • Number of events 2 • 3 years, 3 months
|
Additional Information
Dr. Lauren M Jansson
Johns Hopkins University School of Medicine
Phone: 410-550-5438
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place