Trial Outcomes & Findings for Can Ondansetron Prevent Neonatal Abstinence Syndrome (NAS) in Babies Born to Narcotic-dependent Women (NCT NCT01965704)
NCT ID: NCT01965704
Last Updated: 2022-06-07
Results Overview
The incidence of neonatal abstinence syndrome (NAS) measured as the number of neonates who need for morphine treatment for the symptoms of neonatal opioid withdrawal syndrome (NOWS) while the neonates received study medication and for the 30 days after stopping the study medication.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
196 participants
Primary outcome timeframe
35 days
Results posted on
2022-06-07
Participant Flow
Participant milestones
| Measure |
Ondansetron - Mothers
Pregnant Women: ondansetron 8mg intravenously (IV) within 4 hours of delivery; may receive a second dose of IV ondansetron if they have not delivered within 4 hours of receiving the IV study medication.
|
Ondansetron - Neonates
Neonates: ondansetron 0.07 mg/kg given orally every 24 hours starting 4-8 hours after delivery, for up to 5 days (if IV line available in neonate, ondansetron 0.04 mg/kg IV every 24 hours for up to 5 days).
|
Placebo - Mothers
Pregnant Women: placebo given intravenously prior to delivery (volume to mimic the IV volume of the ondansetron group); may receive a second dose of IV placebo if they have not delivered within 4 hours of being given the IV study medication.
|
Placebo - Neonates
Neonates: placebo given orally every 24 hours, starting 4-8 hours after delivery, for up to 5 days with volume to mimic the oral volume of the ondansetron group (if IV line available, placebo may be given IV).
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
48
|
48
|
50
|
50
|
|
Overall Study
Received Intervention
|
45
|
45
|
47
|
47
|
|
Overall Study
Analyzable Population
|
45
|
45
|
41
|
41
|
|
Overall Study
COMPLETED
|
45
|
45
|
45
|
45
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
5
|
5
|
Reasons for withdrawal
| Measure |
Ondansetron - Mothers
Pregnant Women: ondansetron 8mg intravenously (IV) within 4 hours of delivery; may receive a second dose of IV ondansetron if they have not delivered within 4 hours of receiving the IV study medication.
|
Ondansetron - Neonates
Neonates: ondansetron 0.07 mg/kg given orally every 24 hours starting 4-8 hours after delivery, for up to 5 days (if IV line available in neonate, ondansetron 0.04 mg/kg IV every 24 hours for up to 5 days).
|
Placebo - Mothers
Pregnant Women: placebo given intravenously prior to delivery (volume to mimic the IV volume of the ondansetron group); may receive a second dose of IV placebo if they have not delivered within 4 hours of being given the IV study medication.
|
Placebo - Neonates
Neonates: placebo given orally every 24 hours, starting 4-8 hours after delivery, for up to 5 days with volume to mimic the oral volume of the ondansetron group (if IV line available, placebo may be given IV).
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
1
|
1
|
|
Overall Study
Delivered at home
|
1
|
1
|
0
|
0
|
|
Overall Study
Experienced complications
|
0
|
0
|
2
|
2
|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
1
|
|
Overall Study
Did not meet inclusion criteria
|
0
|
0
|
1
|
1
|
Baseline Characteristics
Gestational age at birth was assessed in the neonates only.
Baseline characteristics by cohort
| Measure |
Ondansetron - Mothers
n=45 Participants
Pregnant Women: ondansetron 8mg intravenously (IV) within 4 hours of delivery; may receive a second dose of IV ondansetron if they have not delivered within 4 hours of receiving the IV study medication.
|
Ondansetron - Neonates
n=45 Participants
Neonates: ondansetron 0.07 mg/kg given orally every 24 hours starting 4-8 hours after delivery, for up to 5 days (if IV line available in neonate, ondansetron 0.04 mg/kg IV every 24 hours for up to 5 days).
|
Placebo - Mothers
n=41 Participants
Pregnant Women: placebo given intravenously prior to delivery (volume to mimic the IV volume of the ondansetron group); may receive a second dose of IV placebo if they have not delivered within 4 hours of being given the IV study medication.
|
Placebo - Neonates
n=41 Participants
Neonates: placebo given orally every 24 hours, starting 4-8 hours after delivery, for up to 5 days with volume to mimic the oral volume of the ondansetron group (if IV line available, placebo may be given IV).
|
Total
n=172 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=45 Participants
|
45 Participants
n=45 Participants
|
0 Participants
n=41 Participants
|
41 Participants
n=41 Participants
|
86 Participants
n=172 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
45 Participants
n=45 Participants
|
0 Participants
n=45 Participants
|
41 Participants
n=41 Participants
|
0 Participants
n=41 Participants
|
86 Participants
n=172 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=45 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=172 Participants
|
|
Sex: Female, Male
Female
|
45 Participants
n=45 Participants
|
22 Participants
n=45 Participants
|
41 Participants
n=41 Participants
|
19 Participants
n=41 Participants
|
127 Participants
n=172 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=45 Participants
|
23 Participants
n=45 Participants
|
0 Participants
n=41 Participants
|
22 Participants
n=41 Participants
|
45 Participants
n=172 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=45 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=172 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=45 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=172 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=45 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=172 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=45 Participants
|
6 Participants
n=45 Participants
|
4 Participants
n=41 Participants
|
4 Participants
n=41 Participants
|
20 Participants
n=172 Participants
|
|
Race (NIH/OMB)
White
|
35 Participants
n=45 Participants
|
35 Participants
n=45 Participants
|
34 Participants
n=41 Participants
|
34 Participants
n=41 Participants
|
138 Participants
n=172 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=45 Participants
|
1 Participants
n=45 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=41 Participants
|
2 Participants
n=172 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=45 Participants
|
3 Participants
n=45 Participants
|
3 Participants
n=41 Participants
|
3 Participants
n=41 Participants
|
12 Participants
n=172 Participants
|
|
Region of Enrollment
United States
|
45 Participants
n=45 Participants
|
45 Participants
n=45 Participants
|
41 Participants
n=41 Participants
|
41 Participants
n=41 Participants
|
172 Participants
n=172 Participants
|
|
Gestational age at birth
|
—
|
39 weeks
n=45 Participants • Gestational age at birth was assessed in the neonates only.
|
—
|
39 weeks
n=41 Participants • Gestational age at birth was assessed in the neonates only.
|
39 weeks
n=86 Participants • Gestational age at birth was assessed in the neonates only.
|
PRIMARY outcome
Timeframe: 35 daysPopulation: Neonates who completed the protocol and met all inclusion criteria are included in the analysis.
The incidence of neonatal abstinence syndrome (NAS) measured as the number of neonates who need for morphine treatment for the symptoms of neonatal opioid withdrawal syndrome (NOWS) while the neonates received study medication and for the 30 days after stopping the study medication.
Outcome measures
| Measure |
Ondansetron - Neonates
n=45 Participants
Neonates: ondansetron 0.07 mg/kg given orally every 24 hours starting 4-8 hours after delivery, for up to 5 days (if IV line available in neonate, ondansetron 0.04 mg/kg IV every 24 hours for up to 5 days).
|
Placebo - Neonates
n=41 Participants
Neonates: placebo given orally every 24 hours, starting 4-8 hours after delivery, for up to 5 days with volume to mimic the oral volume of the ondansetron group (if IV line available, placebo may be given IV).
|
|---|---|---|
|
Number of Participants With Neonatal Abstinence Syndrome
|
22 Participants
|
26 Participants
|
SECONDARY outcome
Timeframe: At Day 15 and up to 64 daysPopulation: Neonates who completed the protocol and met all inclusion criteria are included in the analysis.
Severity of NAS will be measured by neonates' length of hospital stay (birth to discharge). Length of stay was calculated with 1) no maximum length, and 2) maximum length of stay capped at 15 days. All participants were included in both analyses.
Outcome measures
| Measure |
Ondansetron - Neonates
n=45 Participants
Neonates: ondansetron 0.07 mg/kg given orally every 24 hours starting 4-8 hours after delivery, for up to 5 days (if IV line available in neonate, ondansetron 0.04 mg/kg IV every 24 hours for up to 5 days).
|
Placebo - Neonates
n=41 Participants
Neonates: placebo given orally every 24 hours, starting 4-8 hours after delivery, for up to 5 days with volume to mimic the oral volume of the ondansetron group (if IV line available, placebo may be given IV).
|
|---|---|---|
|
Length of Hospital Stay
Mean hospital stay
|
15.5 days
Interval 2.0 to 64.0
|
17.4 days
Interval 3.0 to 63.0
|
|
Length of Hospital Stay
Mean hospital stay with a 15-day maximum
|
9.3 days
Interval 2.0 to 15.0
|
11.2 days
Interval 3.0 to 15.0
|
SECONDARY outcome
Timeframe: 15 daysPopulation: Neonates who completed the protocol and met all inclusion criteria are included in the analysis.
Median dose of morphine required by neonates within 15 days of delivery.
Outcome measures
| Measure |
Ondansetron - Neonates
n=45 Participants
Neonates: ondansetron 0.07 mg/kg given orally every 24 hours starting 4-8 hours after delivery, for up to 5 days (if IV line available in neonate, ondansetron 0.04 mg/kg IV every 24 hours for up to 5 days).
|
Placebo - Neonates
n=41 Participants
Neonates: placebo given orally every 24 hours, starting 4-8 hours after delivery, for up to 5 days with volume to mimic the oral volume of the ondansetron group (if IV line available, placebo may be given IV).
|
|---|---|---|
|
Total Dose of Narcotic Required to Treat the Symptoms of NAS
|
9.3 mg
Interval 0.8 to 37.4
|
11.1 mg
Interval 0.8 to 31.1
|
SECONDARY outcome
Timeframe: 15 daysPopulation: Neonates who completed the protocol and met all inclusion criteria are included in the analysis.
Number of neonates requiring treatment with phenobarbital or clonidine.
Outcome measures
| Measure |
Ondansetron - Neonates
n=45 Participants
Neonates: ondansetron 0.07 mg/kg given orally every 24 hours starting 4-8 hours after delivery, for up to 5 days (if IV line available in neonate, ondansetron 0.04 mg/kg IV every 24 hours for up to 5 days).
|
Placebo - Neonates
n=41 Participants
Neonates: placebo given orally every 24 hours, starting 4-8 hours after delivery, for up to 5 days with volume to mimic the oral volume of the ondansetron group (if IV line available, placebo may be given IV).
|
|---|---|---|
|
Number of Participants Requiring Adjunctive Medication to Treat NOWS
|
5 Participants
|
5 Participants
|
Adverse Events
Ondansetron - Mothers
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Ondansetron - Neonates
Serious events: 2 serious events
Other events: 18 other events
Deaths: 0 deaths
Placebo - Mothers
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo - Neonates
Serious events: 4 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ondansetron - Mothers
n=48 participants at risk
Pregnant Women: ondansetron 8mg intravenously (IV) within 4 hours of delivery; may receive a second dose of IV ondansetron if they have not delivered within 4 hours of receiving the IV study medication.
|
Ondansetron - Neonates
n=48 participants at risk
Neonates: ondansetron 0.07 mg/kg given orally every 24 hours starting 4-8 hours after delivery, for up to 5 days (if IV line available in neonate, ondansetron 0.04 mg/kg IV every 24 hours for up to 5 days).
|
Placebo - Mothers
n=50 participants at risk
Pregnant Women: placebo given intravenously prior to delivery (volume to mimic the IV volume of the ondansetron group); may receive a second dose of IV placebo if they have not delivered within 4 hours of being given the IV study medication.
|
Placebo - Neonates
n=50 participants at risk
Neonates: placebo given orally every 24 hours, starting 4-8 hours after delivery, for up to 5 days with volume to mimic the oral volume of the ondansetron group (if IV line available, placebo may be given IV).
|
|---|---|---|---|---|
|
Nervous system disorders
Hypoxic encephalopathy
|
0.00%
0/48 • 35 days
|
0.00%
0/48 • 35 days
|
0.00%
0/50 • 35 days
|
2.0%
1/50 • 35 days
|
|
Injury, poisoning and procedural complications
Readmission for NOWS observation
|
0.00%
0/48 • 35 days
|
0.00%
0/48 • 35 days
|
0.00%
0/50 • 35 days
|
4.0%
2/50 • 35 days
|
|
Hepatobiliary disorders
Hyperbilirubinemia
|
0.00%
0/48 • 35 days
|
0.00%
0/48 • 35 days
|
0.00%
0/50 • 35 days
|
2.0%
1/50 • 35 days
|
|
Psychiatric disorders
Suicidal Ideation
|
2.1%
1/48 • 35 days
|
0.00%
0/48 • 35 days
|
0.00%
0/50 • 35 days
|
0.00%
0/50 • 35 days
|
|
Infections and infestations
C-section superficial wound infection
|
0.00%
0/48 • 35 days
|
0.00%
0/48 • 35 days
|
2.0%
1/50 • 35 days
|
0.00%
0/50 • 35 days
|
|
Injury, poisoning and procedural complications
Late onset NOWS
|
0.00%
0/48 • 35 days
|
2.1%
1/48 • 35 days
|
0.00%
0/50 • 35 days
|
0.00%
0/50 • 35 days
|
|
Nervous system disorders
Intermittent seizures
|
0.00%
0/48 • 35 days
|
2.1%
1/48 • 35 days
|
0.00%
0/50 • 35 days
|
0.00%
0/50 • 35 days
|
Other adverse events
| Measure |
Ondansetron - Mothers
n=48 participants at risk
Pregnant Women: ondansetron 8mg intravenously (IV) within 4 hours of delivery; may receive a second dose of IV ondansetron if they have not delivered within 4 hours of receiving the IV study medication.
|
Ondansetron - Neonates
n=48 participants at risk
Neonates: ondansetron 0.07 mg/kg given orally every 24 hours starting 4-8 hours after delivery, for up to 5 days (if IV line available in neonate, ondansetron 0.04 mg/kg IV every 24 hours for up to 5 days).
|
Placebo - Mothers
n=50 participants at risk
Pregnant Women: placebo given intravenously prior to delivery (volume to mimic the IV volume of the ondansetron group); may receive a second dose of IV placebo if they have not delivered within 4 hours of being given the IV study medication.
|
Placebo - Neonates
n=50 participants at risk
Neonates: placebo given orally every 24 hours, starting 4-8 hours after delivery, for up to 5 days with volume to mimic the oral volume of the ondansetron group (if IV line available, placebo may be given IV).
|
|---|---|---|---|---|
|
Pregnancy, puerperium and perinatal conditions
Subcutaneous hematoma drainage from C-section incision
|
0.00%
0/48 • 35 days
|
0.00%
0/48 • 35 days
|
2.0%
1/50 • 35 days
|
0.00%
0/50 • 35 days
|
|
Pregnancy, puerperium and perinatal conditions
Vaginal bleeding
|
2.1%
1/48 • 35 days
|
0.00%
0/48 • 35 days
|
0.00%
0/50 • 35 days
|
0.00%
0/50 • 35 days
|
|
Cardiac disorders
Prolonged QTc interval
|
0.00%
0/48 • 35 days
|
29.2%
14/48 • 35 days
|
0.00%
0/50 • 35 days
|
24.0%
12/50 • 35 days
|
|
Cardiac disorders
Short QTc interval
|
0.00%
0/48 • 35 days
|
6.2%
3/48 • 35 days
|
0.00%
0/50 • 35 days
|
4.0%
2/50 • 35 days
|
|
Cardiac disorders
Cyanotic episode
|
0.00%
0/48 • 35 days
|
2.1%
1/48 • 35 days
|
0.00%
0/50 • 35 days
|
0.00%
0/50 • 35 days
|
|
Nervous system disorders
Seizure
|
0.00%
0/48 • 35 days
|
0.00%
0/48 • 35 days
|
0.00%
0/50 • 35 days
|
2.0%
1/50 • 35 days
|
|
Infections and infestations
Sepsis
|
0.00%
0/48 • 35 days
|
0.00%
0/48 • 35 days
|
0.00%
0/50 • 35 days
|
2.0%
1/50 • 35 days
|
|
Respiratory, thoracic and mediastinal disorders
Laryngomalacia
|
0.00%
0/48 • 35 days
|
0.00%
0/48 • 35 days
|
0.00%
0/50 • 35 days
|
2.0%
1/50 • 35 days
|
|
Nervous system disorders
Left brachial plexus injury
|
0.00%
0/48 • 35 days
|
0.00%
0/48 • 35 days
|
0.00%
0/50 • 35 days
|
2.0%
1/50 • 35 days
|
|
Cardiac disorders
Secundum atrial septal defect
|
0.00%
0/48 • 35 days
|
2.1%
1/48 • 35 days
|
0.00%
0/50 • 35 days
|
0.00%
0/50 • 35 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place