Neonatal Abstinence Syndrome
Conditions
Keywords
Prenatal opiate exposure, neonatal withdrawal, Pharmacologic treatment
Brief summary
The purpose of this study is to compare two different medicines to treat babies with opiate withdrawal. The treatment medicines are morphine, which is an opiate, and clonidine, a non-opiate. Morphine is a narcotic medicine, with is included in most pain killers. Clonidine is another drug, but is different from morphine. It is also used for babies, and even adults for withdrawal symptoms. Both drugs are effective, but the purpose of this study is to see if one may be better than the other.
Detailed description
Withdrawal from drugs, called Neonatal abstinence syndrome (NAS), is a group of symptoms that occurs to babies whose mother took or used drugs (prescription, addicting, illegal, pain pills, or drugs for addiction treatment) during pregnancy. Medicines the mother takes while pregnant, the baby also takes. Babies may experience withdrawal after delivery, and may need treatment. There are different ways to treat babies with withdrawal - about 50% of doctors use morphine, an opiate, to treat these babies, the rest uses other drugs, like clonidine and phenobarbitol.
Interventions
DRUGMorphine
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.
DRUGClonidine
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.
Sponsors
Henrietta Bada
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Days to 7 Days
Healthy volunteers
No
Inclusion criteria
* Admitted to Neonatal Intensive Care Unit (NICU)- Gestational age (GA) \>or= 35 wks * Known prenatal opiate exposure (maternal history, positive opiate screen, positive neonatal urine or meconium screen) * Symptomatic with Finnegan Neonatal Abstinence Scores meeting NICU protocol for treatment
Exclusion criteria
* Seizures * Major congenital malformations * Unlikely to survive * Parents not able to understand English
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Finnegan Neonatal Abstinence Scoring System | 14 days | 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. |
| Duration of Treatment | 120 days | Total number days of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | 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. |
| Bayley Scales of Infant and Toddler Development Third Edition | 1 year of life | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 15 |
| 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. | 16 |
| Total | 31 |
Baseline characteristics
| Characteristic | Morphine | Clonidine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 15 Participants | 16 Participants | 31 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 15 participants | 19 participants | 34 participants |
| Sex: Female, Male Female | 8 Participants | 10 Participants | 18 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 16 |
| other Total, other adverse events | 0 / 15 | 0 / 16 |
| serious Total, serious adverse events | 0 / 15 | 0 / 16 |
Outcome results
Primary
Duration of Treatment
Total number days of treatment
Time frame: 120 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Morphine | Duration of Treatment | 39 days |
| Clonidine | Duration of Treatment | 27 days |
Primary
Finnegan Neonatal Abstinence Scoring System
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.
Time frame: 14 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Morphine | Finnegan Neonatal Abstinence Scoring System | Finnegan scores day 2 of treatment | 7.5 scores on a scale | Standard Deviation 0.35 |
| Morphine | Finnegan Neonatal Abstinence Scoring System | Finnegan scores day 7 of treatment | 6.6 scores on a scale | Standard Deviation 0.65 |
| Morphine | Finnegan Neonatal Abstinence Scoring System | Finnegan scores day 14 of treatment | 7.1 scores on a scale | Standard Deviation 1.1 |
| Clonidine | Finnegan Neonatal Abstinence Scoring System | Finnegan scores day 2 of treatment | 8.5 scores on a scale | Standard Deviation 0.3 |
| Clonidine | Finnegan Neonatal Abstinence Scoring System | Finnegan scores day 7 of treatment | 5.7 scores on a scale | Standard Deviation 0.44 |
| Clonidine | Finnegan Neonatal Abstinence Scoring System | Finnegan scores day 14 of treatment | 6.7 scores on a scale | Standard Deviation 0.98 |
Secondary
Bayley Scales of Infant and Toddler Development Third Edition
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
Time frame: 1 year of life
Population: The above number fo reach arm represents the number of subjects who came for follow-up evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Morphine | Bayley Scales of Infant and Toddler Development Third Edition | Cognitive | 92.9 scores on a scale | Standard Deviation 8.4 |
| Morphine | Bayley Scales of Infant and Toddler Development Third Edition | Language Receptive | 101.1 scores on a scale | Standard Deviation 14.3 |
| Morphine | Bayley Scales of Infant and Toddler Development Third Edition | Language total | 98.0 scores on a scale | Standard Deviation 13.8 |
| Morphine | Bayley Scales of Infant and Toddler Development Third Edition | Language Expressive | 100.0 scores on a scale | Standard Deviation 13.1 |
| Morphine | Bayley Scales of Infant and Toddler Development Third Edition | Bayley III motor | 97.6 scores on a scale | Standard Deviation 10.4 |
| Clonidine | Bayley Scales of Infant and Toddler Development Third Edition | Language Expressive | 99.2 scores on a scale | Standard Deviation 13.6 |
| Clonidine | Bayley Scales of Infant and Toddler Development Third Edition | Bayley III motor | 95.8 scores on a scale | Standard Deviation 7.2 |
| Clonidine | Bayley Scales of Infant and Toddler Development Third Edition | Cognitive | 93.3 scores on a scale | Standard Deviation 7.2 |
| Clonidine | Bayley Scales of Infant and Toddler Development Third Edition | Language total | 95.8 scores on a scale | Standard Deviation 10.4 |
| Clonidine | Bayley Scales of Infant and Toddler Development Third Edition | Language Receptive | 95.0 scores on a scale | Standard Deviation 12.2 |
Secondary
Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)
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.
Time frame: 5-10 days after treatment starts
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Morphine | 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 |
| Morphine | 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 |
| Morphine | 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 |
| Morphine | 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 |
| Morphine | 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 |
| Morphine | 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 |
| Morphine | 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 |
| Morphine | 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 |
| Morphine | 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 |
| Morphine | 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 |
| Morphine | 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 |
| Morphine | Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | Lethargy | 3.6 scores on a scale | Standard Error 0.5 |
| Clonidine | Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | Excitability | 2.38 scores on a scale | Standard Error 0.51 |
| Clonidine | Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | Attention | 4.51 scores on a scale | Standard Error 0.26 |
| Clonidine | Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | Stress/abstinence | 0.08 scores on a scale | Standard Error 0.01 |
| Clonidine | Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | Handling | 0.42 scores on a scale | Standard Error 0.06 |
| Clonidine | Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | Hypotonicity | 0.19 scores on a scale | Standard Error 0.13 |
| Clonidine | Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | Quality of movement | 4.92 scores on a scale | Standard Error 0.14 |
| Clonidine | Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | Arousal | 3.95 scores on a scale | Standard Error 0.13 |
| Clonidine | Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | Regulation | 5.26 scores on a scale | Standard Error 0.17 |
| Clonidine | Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | Lethargy | 5.13 scores on a scale | Standard Error 0.03 |
| Clonidine | Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | Non-optimal reflexes | 4.13 scores on a scale | Standard Error 0.4 |
| Clonidine | Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | Hypertonicity | 0.25 scores on a scale | Standard Error 0.24 |
| Clonidine | Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | Asymmetric reflexes | 0.00 scores on a scale | Standard Error 0.14 |