Trial Outcomes & Findings for Trial to Shorten Pharmacologic Treatment of Newborns With Neonatal Opioid Withdrawal Syndrome (NOWS) (NCT NCT04214834)
NCT ID: NCT04214834
Last Updated: 2025-03-13
Results Overview
The number of days of opioid treatment (used as primary treatment), including escalation, resumption, and spot treatment, from the first weaning dose to cessation of opioid. From the start of opioid study medication until weaning. Infants will exit the study intervention without unblinding (remain in the trial) if they have not weaned off study drug by 35 days (inclusive of the 35th day) form the first weaning dose. Outcome will be truncated at 35 days regardless of the study arm.We note that primary outcome data is missing for 4 participants resulting in total sample of 185 for the primary analysis.
ACTIVE_NOT_RECRUITING
PHASE3
189 participants
From the start of opioid study medication until weaning. Infants exited the study intervention without unblinding (remained in the trial) by 35 days from the first weaning dose. Outcome truncated at 35 days regardless of the study arm.
2025-03-13
Participant Flow
Participant milestones
| Measure |
Rapid Wean
Rapid Wean: 15% decrements from the stabilization dose of morphine/methadone
|
Slow Wean
Slow Wean: 10% decrements from the stabilization dose of morphine/methadone
|
|---|---|---|
|
Overall Study
STARTED
|
98
|
91
|
|
Overall Study
COMPLETED
|
94
|
91
|
|
Overall Study
NOT COMPLETED
|
4
|
0
|
Reasons for withdrawal
| Measure |
Rapid Wean
Rapid Wean: 15% decrements from the stabilization dose of morphine/methadone
|
Slow Wean
Slow Wean: 10% decrements from the stabilization dose of morphine/methadone
|
|---|---|---|
|
Overall Study
Withdrawal by Parent(s)/Legal Guardian(s)
|
4
|
0
|
Baseline Characteristics
Trial to Shorten Pharmacologic Treatment of Newborns With Neonatal Opioid Withdrawal Syndrome (NOWS)
Baseline characteristics by cohort
| Measure |
Rapid Wean
n=98 Participants
Rapid Wean: 15% decrements from the stabilization dose of morphine/methadone
|
Slow Wean
n=91 Participants
Slow Wean: 10% decrements from the stabilization dose of morphine/methadone
|
Total
n=189 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.8 weeks
STANDARD_DEVIATION 1.2 • n=99 Participants
|
38.8 weeks
STANDARD_DEVIATION 1.3 • n=107 Participants
|
38.8 weeks
STANDARD_DEVIATION 1.2 • n=206 Participants
|
|
Sex/Gender, Customized
Female
|
39 Participants
n=99 Participants
|
35 Participants
n=107 Participants
|
74 Participants
n=206 Participants
|
|
Sex/Gender, Customized
Male
|
58 Participants
n=99 Participants
|
56 Participants
n=107 Participants
|
114 Participants
n=206 Participants
|
|
Sex/Gender, Customized
Missing
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
American Indian or AlaskaNative
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
16 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Missing
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
More than one race
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
3 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
74 Participants
n=99 Participants
|
74 Participants
n=107 Participants
|
148 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
17 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
77 Participants
n=99 Participants
|
66 Participants
n=107 Participants
|
143 Participants
n=206 Participants
|
|
Mothers opioid treatment
Buprenorphine w/wo naloxone
|
40 Participants
n=99 Participants
|
30 Participants
n=107 Participants
|
70 Participants
n=206 Participants
|
|
Mothers opioid treatment
Methadone
|
32 Participants
n=99 Participants
|
38 Participants
n=107 Participants
|
70 Participants
n=206 Participants
|
|
Mothers opioid treatment
Missing
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Mothers opioid treatment
None/Other
|
25 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
47 Participants
n=206 Participants
|
|
Stabilization dose: Morphine
|
0.22 mg
n=99 Participants
|
0.25 mg
n=107 Participants
|
0.23 mg
n=206 Participants
|
|
Stabilization dose: Methadone
|
0.28 mg
n=99 Participants
|
0.33 mg
n=107 Participants
|
0.31 mg
n=206 Participants
|
|
Infant feed
unknown
|
7 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Infant feed
Bottle
|
76 Participants
n=99 Participants
|
80 Participants
n=107 Participants
|
156 Participants
n=206 Participants
|
|
Infant feed
Breast
|
15 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: From the start of opioid study medication until weaning. Infants exited the study intervention without unblinding (remained in the trial) by 35 days from the first weaning dose. Outcome truncated at 35 days regardless of the study arm.Population: An intent-to-treat (ITT) analysis which included all infants participants who were randomized and who provided outcome data.
The number of days of opioid treatment (used as primary treatment), including escalation, resumption, and spot treatment, from the first weaning dose to cessation of opioid. From the start of opioid study medication until weaning. Infants will exit the study intervention without unblinding (remain in the trial) if they have not weaned off study drug by 35 days (inclusive of the 35th day) form the first weaning dose. Outcome will be truncated at 35 days regardless of the study arm.We note that primary outcome data is missing for 4 participants resulting in total sample of 185 for the primary analysis.
Outcome measures
| Measure |
Rapid Wean
n=94 Participants
Rapid Wean: 15% decrements from the stabilization dose of morphine/methadone
|
Slow Wean
n=91 Participants
Slow Wean: 10% decrements from the stabilization dose of morphine/methadone
|
|---|---|---|
|
Days of Opioid Treatment From First Wean to Cessation
|
9.3 days
Standard Deviation 6.3
|
11.7 days
Standard Deviation 6.1
|
SECONDARY outcome
Timeframe: From the start of opioid study medication until weaning. Infants exited the study intervention without unblinding (remained in the trial) by 35 days from the first weaning dose. Outcome truncated at 35 days regardless of the study arm.Population: An intent-to-treat (ITT) analysis which included all infants participants who were randomized and who provided outcome data.
The number of days of opioid treatment from first wean to cessation among infants that were not withdrawn in high enrolling centers
Outcome measures
| Measure |
Rapid Wean
n=65 Participants
Rapid Wean: 15% decrements from the stabilization dose of morphine/methadone
|
Slow Wean
n=69 Participants
Slow Wean: 10% decrements from the stabilization dose of morphine/methadone
|
|---|---|---|
|
Days of Opioid Treatment From First Wean to Cessation Among Infants That Were Not Withdrawn in High Enrolling Centers
|
8.1 days
Standard Deviation 4.9
|
10.5 days
Standard Deviation 4.2
|
SECONDARY outcome
Timeframe: From the start of opioid study medication until weaning. Infants exited the study intervention without unblinding (remained in the trial) by 35 days from the first weaning dose. Outcome truncated at 35 days regardless of the study arm.Population: An intent-to-treat (ITT) analysis which included all infants participants who were randomized and who provided outcome data.
The number of days of opioid treatment from first wean to cessation among high enrolling centers
Outcome measures
| Measure |
Rapid Wean
n=72 Participants
Rapid Wean: 15% decrements from the stabilization dose of morphine/methadone
|
Slow Wean
n=76 Participants
Slow Wean: 10% decrements from the stabilization dose of morphine/methadone
|
|---|---|---|
|
Days of Opioid Treatment From First Wean to Cessation Among High Enrolling Centers
|
9 days
Standard Deviation 5.9
|
11.3 days
Standard Deviation 5.7
|
SECONDARY outcome
Timeframe: From the start of opioid study medication until weaning. Infants exited the study intervention without unblinding (remained in the trial) by 35 days from the first weaning dose. Outcome truncated at 35 days regardless of the study arm.Population: An intent-to-treat (ITT) analysis which included all infants participants who were randomized and who provided outcome data.
The number of days of opioid treatment from first wean to cessation among infants that were not withdrawn
Outcome measures
| Measure |
Rapid Wean
n=80 Participants
Rapid Wean: 15% decrements from the stabilization dose of morphine/methadone
|
Slow Wean
n=79 Participants
Slow Wean: 10% decrements from the stabilization dose of morphine/methadone
|
|---|---|---|
|
Days of Opioid Treatment From First Wean to Cessation Among Infants That Were Not Withdrawn
|
8 days
Standard Deviation 4.8
|
10.7 days
Standard Deviation 4.1
|
Adverse Events
Rapid Wean
Slow Wean
Serious adverse events
| Measure |
Rapid Wean
n=98 participants at risk
Rapid Wean: 15% decrements from the stabilization dose of morphine/methadone
|
Slow Wean
n=91 participants at risk
Slow Wean: 10% decrements from the stabilization dose of morphine/methadone
|
|---|---|---|
|
Nervous system disorders
Epidural hematoma
|
0.00%
0/98 • Randomization through 8-weeks post discharge
|
1.1%
1/91 • Number of events 1 • Randomization through 8-weeks post discharge
|
|
Nervous system disorders
Seizure
|
1.0%
1/98 • Number of events 1 • Randomization through 8-weeks post discharge
|
0.00%
0/91 • Randomization through 8-weeks post discharge
|
|
Nervous system disorders
Skull fracture
|
0.00%
0/98 • Randomization through 8-weeks post discharge
|
1.1%
1/91 • Number of events 1 • Randomization through 8-weeks post discharge
|
Other adverse events
| Measure |
Rapid Wean
n=98 participants at risk
Rapid Wean: 15% decrements from the stabilization dose of morphine/methadone
|
Slow Wean
n=91 participants at risk
Slow Wean: 10% decrements from the stabilization dose of morphine/methadone
|
|---|---|---|
|
Gastrointestinal disorders
Inguinal hernia/repair
|
0.00%
0/98 • Randomization through 8-weeks post discharge
|
1.1%
1/91 • Number of events 1 • Randomization through 8-weeks post discharge
|
|
Nervous system disorders
Over-sedation
|
1.0%
1/98 • Number of events 1 • Randomization through 8-weeks post discharge
|
0.00%
0/91 • Randomization through 8-weeks post discharge
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disturbances
|
2.0%
2/98 • Number of events 2 • Randomization through 8-weeks post discharge
|
3.3%
3/91 • Number of events 3 • Randomization through 8-weeks post discharge
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place