Neonatal Abstinence Syndrome
Conditions
Brief summary
The purpose of this study is to compare clonidine versus phenobarbital as adjunctive therapy in those infants who have failed monotherapy with morphine sulfate for neonatal abstinence syndrome (NAS).
Interventions
DRUGPhenobarbital
Phenobarbital loading dose 20 mg/kg in 2 divided doses, then 5 mg/kg/day divided every 12 hours. Phenobarbital dose will be adjusted to obtain desired trough of 25 to 30 mcg/mL. Levels will be obtained on Day 6 then weekly thereafter. Phenobarbital will be tapered over 4 weeks upon discharge from the hospital. The standardized taper is based the patient specific dose at the time of discharge.
DRUGClonidine
Clonidine 5 mcg/kg/day divided every 3 hours. Clonidine will be increased by 1.5 mcg/kg/day to achieve control of NAS symptoms based upon standardized scoring for neonatal abstinence syndrome. Clonidine will be weaned by 25% every 24 hours after successful discontinuation of oral morphine sulfate. Infants will not be discharged on clonidine.
Sponsors
University of Tennessee Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
35 Weeks to No maximum
Healthy volunteers
No
Inclusion criteria
* Infants greater than or equal to 35 weeks gestation age * Admitted to the neonatal intensive care unit * Failed monotherapy with morphine sulfate therapy
Exclusion criteria
* Neonatal abstinence syndrome due to iatrogenic causes * Unable to take oral medications at any point during their treatment * Infants in the custody of the Department of Child Protective Services with no legal guardian identified at the time of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Initiation of Adjunctive Therapy Until Hospital Discharge | From date of randomization until hospital discharge, up to 4 months | Number of days from initiation of adjunctive therapy until hospital discharge |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Stay | From date of randomization until hospital discharge, up to 4 months | Number of days of hospital admission |
| Length of Oral Morphine Sulfate Therapy | From date of randomization until hospital discharge, up to 4 months | Number of days of oral morphine sulfate therapy |
| Number of Patients Requiring Triple Therapy | From date of randomization until hospital discharge, up to 4 months | Number of patients requiring a third agent to control withdrawal symptoms |
| Readmission Rate | From date of randomization until 30 days after hospital discharge or discontinuation of phenobarbital, up to 6 months | Number of patients readmitted to the hospital within 30 days of hospital discharge or discontinuation of phenobarbital. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phenobarbital Phenobarbital loading dose 20mg/kg in 2 divided doses, then 5 mg/kg/day divided every 12 hours. Phenobarbital continued throughout the infants hospitalization.
Phenobarbital: Phenobarbital loading dose 20 mg/kg in 2 divided doses, then 5 mg/kg/day divided every 12 hours. Phenobarbital dose will be adjusted to obtain desired trough of 25 to 30 mcg/mL. Levels will be obtained on Day 6 then weekly thereafter. Phenobarbital will be tapered over 4 weeks upon discharge from the hospital. The standardized taper is based the patient specific dose at the time of discharge. | 11 |
| Clonidine Clonidine 5 mcg/kg/day divided every 3 hours. Clonidine will be continued to achieve control of NAS symptoms. Clonidine may be weaned after successful discontinuation of oral morphine sulfate. Infants will not be discharged on clonidine.
Clonidine: Clonidine 5 mcg/kg/day divided every 3 hours. Clonidine will be increased by 1.5 mcg/kg/day to achieve control of NAS symptoms based upon standardized scoring for neonatal abstinence syndrome. Clonidine will be weaned by 25% every 24 hours after successful discontinuation of oral morphine sulfate. Infants will not be discharged on clonidine. | 14 |
| Total | 25 |
Baseline characteristics
| Characteristic | Phenobarbital | Total | Clonidine |
|---|---|---|---|
| Age, Categorical <=18 years | 11 Participants | 25 Participants | 14 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 38 Weeks STANDARD_DEVIATION 1 | 38.3 Weeks STANDARD_DEVIATION 1.3 | 38.6 Weeks STANDARD_DEVIATION 1.6 |
| Appearance, Pulse, Grimace, Activity, and Respiration - APGAR scale | 6.7 units on a scale STANDARD_DEVIATION 2.1 | 7.3 units on a scale STANDARD_DEVIATION 1.4 | 7.8 units on a scale STANDARD_DEVIATION 0.9 |
| Birth weight, grams | 3173 Grams STANDARD_DEVIATION 588 | 3155 Grams STANDARD_DEVIATION 549 | 3141 Grams STANDARD_DEVIATION 519 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 25 Participants | 14 Participants |
| Region of Enrollment United States | 11 Participants | 25 Participants | 14 Participants |
| Sex: Female, Male Female | 5 Participants | 12 Participants | 7 Participants |
| Sex: Female, Male Male | 6 Participants | 13 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 14 |
| other Total, other adverse events | 0 / 11 | 3 / 14 |
| serious Total, serious adverse events | 0 / 11 | 0 / 14 |
Outcome results
Primary
Time From Initiation of Adjunctive Therapy Until Hospital Discharge
Number of days from initiation of adjunctive therapy until hospital discharge
Time frame: From date of randomization until hospital discharge, up to 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phenobarbital | Time From Initiation of Adjunctive Therapy Until Hospital Discharge | 20 Days | Standard Deviation 12.6 |
| Clonidine | Time From Initiation of Adjunctive Therapy Until Hospital Discharge | 33.8 Days | Standard Deviation 14.3 |
Secondary
Length of Oral Morphine Sulfate Therapy
Number of days of oral morphine sulfate therapy
Time frame: From date of randomization until hospital discharge, up to 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phenobarbital | Length of Oral Morphine Sulfate Therapy | 25.45 Days | Standard Deviation 6.95 |
| Clonidine | Length of Oral Morphine Sulfate Therapy | 34.36 Days | Standard Deviation 10.18 |
Secondary
Length of Stay
Number of days of hospital admission
Time frame: From date of randomization until hospital discharge, up to 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phenobarbital | Length of Stay | 31 Days | Standard Deviation 9.96 |
| Clonidine | Length of Stay | 41.78 Days | Standard Deviation 10.94 |
Secondary
Number of Patients Requiring Triple Therapy
Number of patients requiring a third agent to control withdrawal symptoms
Time frame: From date of randomization until hospital discharge, up to 4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phenobarbital | Number of Patients Requiring Triple Therapy | 4 participants |
| Clonidine | Number of Patients Requiring Triple Therapy | 10 participants |
Secondary
Readmission Rate
Number of patients readmitted to the hospital within 30 days of hospital discharge or discontinuation of phenobarbital.
Time frame: From date of randomization until 30 days after hospital discharge or discontinuation of phenobarbital, up to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phenobarbital | Readmission Rate | 0 Participants |
| Clonidine | Readmission Rate | 0 Participants |