Clonidine for Neonatal Abstinence Syndrome Study

Neonatal Abstinence Syndrome Clinical Trial

Official title:

Comparison of Clonidine Versus Phenobarbital as an Adjunct Therapy for Neonatal Abstinence Syndrome

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01175668
• Other study ID #: BH-10-196
• Status: Terminated
• Phase: N/A
• First received: July 14, 2010
• Last updated: November 18, 2013
• Start date: July 2010
• Est. completion date: October 2012

Study information

• Verified date: November 2013
• Source: Baystate Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 68
• Est. completion date: October 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 15 Days

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neonatal Abstinence Syndrome
• Syndrome

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	NICU @ Baystate Children's Hospital	Springfield	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Baystate Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (1)

Surran B, Visintainer P, Chamberlain S, Kopcza K, Shah B, Singh R. Efficacy of clonidine versus phenobarbital in reducing neonatal morphine sulfate therapy days for neonatal abstinence syndrome. A prospective randomized clinical trial. J Perinatol. 2013 D — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Length of Treatment With Neonatal Morphine Sulfate		subjects were followed for the duration of treatment, up to 3 months	No
Secondary	Total Dose of NMS Used		For the duration of treatment, upto 3 months	No