Clonidine for Neonatal Abstinence Syndrome Study

This study has been terminated.
(Based on the planned interim analysis results at 50% recruitment, after IRB reviewed the results, further enrollment was stopped.)
Sponsor:
Information provided by (Responsible Party):
Rachana Singh, MD, Baystate Medical Center
ClinicalTrials.gov Identifier:
NCT01175668
First received: July 14, 2010
Last updated: November 18, 2013
Last verified: November 2013
  Purpose

The study plans to compare the use of Clonidine versus Phenobarbital as an additional medication to neonatal morphine sulfate for treatment of newborn infants undergoing drug withdrawal symptoms due to mother's use of opioid drug use. The investigators hypothesis is that use of Clonidine will lead to shorter duration of treatment, hospital stay and thereby early discharge home.


Condition Intervention
Neonatal Abstinence Syndrome
Drug: Clonidine
Drug: Phenobarbital

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparison of Clonidine Versus Phenobarbital as an Adjunct Therapy for Neonatal Abstinence Syndrome

Resource links provided by NLM:


Further study details as provided by Baystate Medical Center:

Primary Outcome Measures:
  • Length of Treatment With Neonatal Morphine Sulfate [ Time Frame: subjects were followed for the duration of treatment, up to 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Total Dose of NMS Used [ Time Frame: For the duration of treatment, upto 3 months ] [ Designated as safety issue: No ]

Enrollment: 68
Study Start Date: July 2010
Study Completion Date: October 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NMS/Clonidine Drug: Clonidine
This group of infants undergoing NAS will be treated with neonatal morphine sulfate and Clonidine as an adjunct medication to control the symptoms. Once stable Finnegan scores <8 for 24h, NMS will be weaned by 10% daily till off, then Clonidine will be weaned off in a stepwise manner. Infant will not go home on any medication for NAS. NMS will be dosed as mg/kd/day divided q3h and Clonidine will be dosed as microgm/kg/day divided q6h based upon the initial Finnegan scores.
Active Comparator: NMS/Phenobarbital Drug: Phenobarbital

Infants in this arm will be treated as current standard practice with NMS and Phenobarbital. NMS will be weaned by 10% daily to completely off during the hospital stay. Infants will be discharged home on Phenobarbital.

NMS will be dosed as mg/kg/day divided q3h and Phenobarbital will be dosed as mg/kg/day divided q8h based on the Finnegan scores.


Detailed Description:

Introduction: Neonatal abstinence syndrome (NAS) is a symptom complex experienced by 55 to 94% of neonates who are exposed to intrauterine opioids. Recent studies have shown that combination therapies are superior to monotherapy with neonatal morphine sulfate (NMS). Phenobarbital has been shown to reduce the length of hospitalization, decrease severity of withdrawal, as well as decrease hospital costs and care giver demands. Similarly, clonidine, an α2-adrenergic receptor agonist, has also been shown to be safe, effective and reduces length of treatment.

Phenobarbital as an antiepileptic acts on the GABA (A) receptors and has been shown in animal models to inhibit neuronal cell proliferation, survival and neurogenesis. In human infants long term treatment with phenobarbital may result in neuro-developmental compromise. Due to these potentially harmful effects of Phenobarbital (P) alternative therapies should be explored more thoroughly including clonidine (C).

Our primary aim is to compare the length of NAS treatment with NMS in the two study groups - NMS/C versus NMS/P. Our secondary aims are to compare the total dosage of NMS, total length of hospital stay for NAS treatment, treatment failures and adverse effect profiles for the two study groups. We hypothesize that clonidine when compared to phenobarbital as an adjunct therapy, will have shorter length of stay, with fewer treatment failures and side effects.

Study design/Methods: This study will be a prospective, randomized, non-blinded clinical trial of NMS/C versus NMS/P for treatment of infants with NAS. Infants will be recruited from the Baystate Children's Hospital Neonatal Intensive Care Unit (NICU) and Neonatal Continuing Care Nursery (NCCN), a level III unit, over a 2 year study period. After randomization, infants will adhere to strict treatment initiation and withdrawal protocols. Maternal and infant descriptive data will be collected along with specific data regarding vital signs, drug dosages, length of treatment, treatment failures and adverse effects.

The primary outcome will be length of treatment with NMS in the two study arms. The secondary outcomes will be - a) total length of hospital stay for NAS treatment, b) mean total treatment dose and mean daily dose of NMS, c) total number of treatment failures,d) adverse effects such as bradycardia, hypotension, hypertension e) Total outpatient therapy days with Phenobarbital

Significance: This comparison study is potentially of great significance. If clonidine is proven to be equally effective in treatment of NAS many of the detrimental effects of phenobarbital therapy may be avoided for infants on long term pharmacotherapy for treatment of withdrawal with shorter length of hospital stay.

  Eligibility

Ages Eligible for Study:   up to 15 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 0 to 15 days of age
  • Prenatal exposure to opioids with development of moderate to severe NAS (2 consecutive abstinence scores of ≥ 8)
  • Medically stable

Exclusion Criteria:

  • Gestational age < 35 weeks
  • Intrauterine growth retardation (birth weight below the 5th percentile)
  • Congenital heart disease
  • Congenital anomalies
  • Medically unstable

Exposure to Benzodiazepines prenatally

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  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01175668

Locations
United States, Massachusetts
NICU @ Baystate Children's Hospital
Springfield, Massachusetts, United States, 01199
Sponsors and Collaborators
Baystate Medical Center
Investigators
Principal Investigator: Rachana Singh, MD, MS Baystate Medical Center
  More Information

Publications:
Responsible Party: Rachana Singh, MD, Assistant Professor of Pediatrics, Baystate Medical Center
ClinicalTrials.gov Identifier: NCT01175668     History of Changes
Other Study ID Numbers: BH-10-196
Study First Received: July 14, 2010
Results First Received: September 3, 2013
Last Updated: November 18, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Neonatal Abstinence Syndrome
Infant, Newborn, Diseases
Substance-Related Disorders
Mental Disorders
Clonidine
Phenobarbital
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Central Nervous System Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
GABA Modulators
GABA Agents
Anticonvulsants

ClinicalTrials.gov processed this record on July 28, 2014