Trial Outcomes & Findings for NAS Treatment - Opiate Versus Non-Opiate (NCT NCT01734551)

Last Updated: 2017-09-12

Results Overview

Mean of total Finnegan Scores obtained every 3 hours on days 2, 7, and 14 following start of treatment; A score is a number representing the total score or sum from 21 items or symptoms or manifestations of opiate withdrawal in newborn infants. The total score ranges from 0 to 43. Reference: 1. Finnegan LP, Connaughton JF, Jr., Kron RE, et al. Neonatal abstinence syndrome: assessment and management. Addict Dis 1975;2(1-2):141-58. Although normal newborn may manifest mild symptoms that will give scores in the range of 0 to 7. A score of 8 consecutively obtained times 3 indicate that infant will benefit from treatment, in this study morphine or clonidine. A decrease in scores especially to less than 8 is suggestive of a good response to treatment.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

31 participants

Primary outcome timeframe

14 days

Results posted on

2017-09-12

Participant Flow

Participant milestones

Participant milestones
Measure	Morphine Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. Morphine: Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day. Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is \<0.1mg/kg/day, may discontinue.	Clonidine Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. Clonidine: Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.
Overall Study STARTED	15	16
Overall Study COMPLETED	15	16
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

NAS Treatment - Opiate Versus Non-Opiate

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Morphine n=15 Participants Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. Morphine: Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day. Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is \<0.1mg/kg/day, may discontinue.	Clonidine n=16 Participants Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. Clonidine: Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.	Total n=31 Participants Total of all reporting groups
Age, Categorical <=18 years	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	19 participants n=7 Participants	34 participants n=5 Participants

PRIMARY outcome

Timeframe: 14 days

Outcome measures

Outcome measures
Measure	Morphine n=15 Participants Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. Morphine: Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day. Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is \<0.1mg/kg/day, may discontinue.	Clonidine n=16 Participants Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. Clonidine: Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.
Finnegan Neonatal Abstinence Scoring System Finnegan scores day 2 of treatment	7.5 scores on a scale Standard Deviation 0.35	8.5 scores on a scale Standard Deviation 0.30
Finnegan Neonatal Abstinence Scoring System Finnegan scores day 7 of treatment	6.6 scores on a scale Standard Deviation 0.65	5.7 scores on a scale Standard Deviation 0.44
Finnegan Neonatal Abstinence Scoring System Finnegan scores day 14 of treatment	7.1 scores on a scale Standard Deviation 1.1	6.7 scores on a scale Standard Deviation 0.98

PRIMARY outcome

Timeframe: 120 days

Total number days of treatment

Outcome measures

Outcome measures
Measure	Morphine n=15 Participants Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. Morphine: Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day. Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is \<0.1mg/kg/day, may discontinue.	Clonidine n=16 Participants Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. Clonidine: Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.
Duration of Treatment	39 days Interval 26.0 to 89.0	27 days Interval 18.0 to 107.0

SECONDARY outcome

Timeframe: 5-10 days after treatment starts

The summary scores from the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) give a measure of infant neurobehavior in the following areas (score range): habituation (1-9), regulation (2.20-7.50), attention (1.29 -8.4), Handling (0 - 1), quality of movement (1.20 - 6.20), Non-optimal reflexes (0-12), Asymmetric reflexes (0-7), arousal (2.43 - 6.67), hypertonicity (0- 8), hypotonicity (0 - 5.0), excitability (0-11), lethargy (0 - 11.0). and stress/abstinence (0. - 0.57). A higher score for each item means a higher level of the construct. For example, a higher score for hypertonicity means the infant is more hypertonic and higher score on hypotonicity means the infant is more hypotonic. No cut-off score published for normal or abnormal behavioral performance. Reference: Lester BM et al. Summary Statistics of Neonatal Intensive Care Unit Network Neurobehavioral Scale Scores From the Maternal Lifestyle Study: A Quasinormative Sample, in Pediatrics 2004; 113,668.

Outcome measures

Outcome measures
Measure	Morphine n=15 Participants Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. Morphine: Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day. Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is \<0.1mg/kg/day, may discontinue.	Clonidine n=16 Participants Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. Clonidine: Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.
Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Attention	5.06 scores on a scale Standard Error 0.27	4.51 scores on a scale Standard Error 0.26
Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Handling	0.36 scores on a scale Standard Error 0.06	0.42 scores on a scale Standard Error 0.06
Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Quality of movement	4.77 scores on a scale Standard Error 0.15	4.92 scores on a scale Standard Error 0.14
Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Regulation	5.2 scores on a scale Standard Error 0.18	5.26 scores on a scale Standard Error 0.17
Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Non-optimal reflexes	3.73 scores on a scale Standard Error 0.42	4.13 scores on a scale Standard Error 0.40
Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Asymmetric reflexes	0.20 scores on a scale Standard Error 0.14	0.00 scores on a scale Standard Error 0.14
Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Stress/abstinence	0.07 scores on a scale Standard Error 0.01	0.08 scores on a scale Standard Error 0.01
Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Arousal	3.91 scores on a scale Standard Error 0.13	3.95 scores on a scale Standard Error 0.13
Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Hypertonicity	0.40 scores on a scale Standard Error 0.25	0.25 scores on a scale Standard Error 0.24
Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Hypotonicity	0.13 scores on a scale Standard Error 0.13	0.19 scores on a scale Standard Error 0.13
Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Excitability	2.6 scores on a scale Standard Error 0.53	2.38 scores on a scale Standard Error 0.51
Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Lethargy	3.6 scores on a scale Standard Error 0.50	5.13 scores on a scale Standard Error 0.03

SECONDARY outcome

Timeframe: 1 year of life

Population: The above number fo reach arm represents the number of subjects who came for follow-up evaluation.

Scores obtained Bayley Scales of Infant and Toddler Development Third Edition in the developmental domains of motor, cognitive, and language. This tool for measures of motor, cognitive and language development is a series of standardized measurements and for each domain, the standardized scores have a mean of 100 and standard deviation of 15. Scores below 1 standard deviation (= or less than 84) is considered below normal. Scores above 1 standard deviation (over 115) represent higher than normal functioning in each domain The score for each domain (motor, cognitive, and language functioning) represents the full-scale score

Outcome measures

Outcome measures
Measure	Morphine n=12 Participants Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. Morphine: Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day. Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is \<0.1mg/kg/day, may discontinue.	Clonidine n=12 Participants Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. Clonidine: Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.
Bayley Scales of Infant and Toddler Development Third Edition Language Expressive	100.0 scores on a scale Standard Deviation 13.1	99.2 scores on a scale Standard Deviation 13.6
Bayley Scales of Infant and Toddler Development Third Edition Language Receptive	101.1 scores on a scale Standard Deviation 14.3	95.0 scores on a scale Standard Deviation 12.2
Bayley Scales of Infant and Toddler Development Third Edition Bayley III motor	97.6 scores on a scale Standard Deviation 10.4	95.8 scores on a scale Standard Deviation 7.2
Bayley Scales of Infant and Toddler Development Third Edition Cognitive	92.9 scores on a scale Standard Deviation 8.4	93.3 scores on a scale Standard Deviation 7.2
Bayley Scales of Infant and Toddler Development Third Edition Language total	98.0 scores on a scale Standard Deviation 13.8	95.8 scores on a scale Standard Deviation 10.4

Adverse Events

Morphine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Clonidine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Henrietta S. Bada, Professor and Vice Chair, Academic Affairs

University of Kentucky

Phone: 859-323-1019

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place