How to Treat Opiate Withdrawal in Neonates

Study Overview
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Brief Summary
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Three different drugs are used in a randomised, double blind, clinical multi-centre trial with three arms. Major objective is to investigate the duration of drug treatment based on the Finnegan score. Secondary objectives are to document weight gain, the need for adding a second drug when the first drug is not effective enough and possible side effects such as convulsions.

Detailed Description
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Background: Neonatal narcotic abstinence syndrome is an important medical, social and financial problem. Several drugs are used to treat the withdrawal symptoms in neonates that have been exposed to opiates in utero, but there is no consensus which one is best. Goal: Three different drugs are used in a randomised, double blind, clinical multi-centre trial with three arms. Major objective is to investigate the duration of drug treatment based on the Finnegan score. Secondary objectives are to document weight gain, the need for adding a second drug when the first drug is not effective enough and possible side effects such as convulsions. Methods: Neonates born after 34 completed weeks of gestation with meconium proven antenatal opiate exposure and parental informed consent are included. Infants with severe malformation are excluded. Each infant is assessed every eight hour by a modified Finnegan score. When 9 points are exceeded drug treatment is started and dose increased stepwise according to the score. The masqued solution applied orally contains morphine, phenobarbital or chlorpromazine. When the maximum dose does not reduce the score, a second randomisation and one of the two remaining drugs is added, again in a blinded way. A total of 120 infants, 40 in each group will be included in the study.

Official Title
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Pharmacological Treatment of Narcotic Neonatal Withdrawal

Conditions
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Neonatal Abstinence Syndrome

Intervention / Treatment
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* Drug: Phenobarbital
* Drug: Chlorpromazine
* Drug: Morphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Neonates of mothers who consumed opiates during pregnancy Born after 34 completed weeks of pregnancy Parents' informed consent Exclusion Criteria: Preterm birth before 34 0/7 gestational weeks Severe malformation Illness requiring respiratory assistance or catecholamines Negative meconium drug test

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 3 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phenobarbital<br>Phenobarbitone loading dose 10 mg/kg body weight maintenance dose 0.83 mg/kg body weight every 4 hours | Drug: Phenobarbital<br>* Phenobarbital per os<br>* Other names: Phenobarbitone;|
| Active Comparator: Chlorpromazine<br>Chlorpromazine loading dose 0.5 mg/kg body weight maintenance dose 0.25 mg/kg every 4 hours | Drug: Chlorpromazine<br>* Chlorpromazine per os<br>* Other names: Largactil;|
| Active Comparator: Morphine<br>Morphine (tinctura opii) 0.25 mg/kg body weight every 4 hours | Drug: Morphine<br>* Morphine per os<br>* Other names: tinctura opii;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of treatment | Treatment is reduced stepwise until withdrawal symptoms have gone | 0 to 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of convulsions |  | Whole time of hospitalisation (up to 10 weeks) | 
| Weight gain |  | through study completion, up to 10 weeks | 
| Treatment failures (need for adding second medication) | Need for additional drug if investigational drug does not control withdrawal symptoms | through study completion, up to 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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newborn, opiate dependence, withdrawal