Non-Opiate Treatment After Prenatal Opiate Exposure to Prevent Postnatal Injury to the Young Brain

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-12-07

Study Completion Date

2024-04-10

Brief Summary

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The long term goals of our research are to establish the best pharmacological treatment for NAS and determine how pharmacologic treatment of NAS affects long-term developmental outcomes. The objective of this application is to evaluate the effectiveness of clonidine as a treatment for neonates with NAS, in a randomized clinical trial. Our central hypothesis is that clonidine will effectively treat drug withdrawal manifestations in neonates.

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Detailed Description

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In this current proposal, the research plan is based on our pilot study, which randomized infants with NAS to receive morphine or clonidine. The treatment groups were similar as to mean birth weight, gestational age, Apgar scores, and postnatal age at treatment. Infants enrolled had no other medical or surgical complications. Treatment was initiated per our NICU standard at the time, and will be continued in this protocol. Total LOS was shorter by about 1 week in the clonidine (mean of 15 days), compared to 21 days in the morphine group.

Aims and Objectives:

To determine whether the treatment of NAS with a non-opiate medication, clonidine, will be more effective than morphine

* Compare Clonidine and morphine for the treatment of NAS. Compare the efficacy of each drug which is determined by duration of treatment in number of days, number of dose escalations needed to achieve needed treatment, and the need for second drug treatment.
* Evaluate the neurobehavioral performance scores (habituation, orientation, self- regulation, motor/reflexes, and stress/ abstinence scales) using the neonatal intensive care (NICU) network neurobehavioral scale (NNNS) in both treatment groups. This exam will take place after treatment begins, and at one month post-natal age (38-44 weeks post menstrual age) or at discharge, whichever comes first.

To determine whether treatment of NAS with clonidine will result in better early childhood outcomes than those treated with morphine • Compare the cognitive, motor and behavioral development of children in both treatment groups using the Bayley III Scales of Infant Development at 6 months, one and two years of age.

To build population pharmacokinetic/pharmacodynamic models and determine factors that affect exposure and response to morphine and clonidine

• Measure blood levels obtained at random times and correlate to Finnegan scores. The pharmacodynamics may help with understanding NAS medications and coping measures in babies.

Conditions

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Neonatal Abstinence Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The study is intended to treat NAS using a randomized and double-blind study design to compare the use of opiate (morphine) or non-opiate (clonidine). Newborns meeting the study criteria for drug withdrawal and treatment will be randomized to receive one of the drugs (morphine, clonidine). Newborns requiring a second drug to help relieve the symptoms will be treated with phenobarbital for both groups. Randomization, blinding and dispensing will occur in the Investigational Drug Services Unit. Nursing personnel in the NICU will be masked to the treatment administered to each baby.

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

The study will mask parents and child caregivers, and NICU nurses giving the drug, other personnel, residents and attending physicians, and research staff. Since initial dose is set using weight based-dosing, a physician's order can be entered in the electronic medical record to give the initial study drug with the infant's weight stated in the order. Increase in dosing will be ordered as to increase by 25% of initial dose or decrease of dose by 10% of maximum dose. During the pilot study, masking of treating personnel was maintained while the hospital pharmacist was the only person aware of which study drug the infant was receiving. The examiners for administration of the NNNS and the research nurse and research case worker will be masked to treatment received. Those seeing the infant in the clinic will also be masked to the treatment assignment. Morphine and clonidine are dispensed in identical appearance, color, smell, and volume.

Study Groups

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Clonidine

Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours).

Group Type ACTIVE_COMPARATOR

Clonidine

Intervention Type DRUG

1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.

Morphine

Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours).

Group Type ACTIVE_COMPARATOR

Morphine

Intervention Type DRUG

Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.

Interventions

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Clonidine

1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.

Intervention Type DRUG

Morphine

Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.

Intervention Type DRUG

Other Intervention Names

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clonidine hydrochloride Morphine Sulfate

Eligibility Criteria

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Inclusion Criteria

* Gestational age (GA) \> or equal to 35 weeks
* Known prenatal opiate exposure (by mother admitting use, mom with positive opiate screen during pregnancy, or positive neonatal urine and meconium screening)
* No known prenatal cocaine exposure
* No morphine or clonidine dose before enrollment
* Symptomatic with Finnegan scores (FS): 3 consecutive scores greater than or equal to 8, OR 2 consecutive scores greater than or equal to 12, and/or with attending decision to treat for NAS
* Less than or equal to 7 days of age
* Attending physician decides to start pharmacologic treatment and agrees to infant's study participation

Exclusion Criteria

* Seizures
* Major congenital malformations
* Blood pressure instability
* Major medical condition in addition to NAS
* Parents unable to understand English

Minimum Eligible Age

12 Hours

Maximum Eligible Age

7 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No