Non-Opiate Treatment After Prenatal Opiate Exposure to Prevent Postnatal Injury to the Young Brain (No-POPPY)

Henrietta Bada

Status and phase

Completed

Phase 3

Conditions

Neonatal Abstinence Syndrome

Treatments

Drug: Clonidine

Drug: Morphine

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT03396588

11-0534-F34

1R01DA043519-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

120 patients

Sex

All

Ages

12 hours to 7 days old

Volunteers

No Healthy Volunteers

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