Neonatal Abstinence SyndromeNCT01175668
Clonidine for Neonatal Abstinence Syndrome Study
A study testing Clonidine and Phenobarbital in people with Neonatal Abstinence Syndrome, run by Baystate Medical Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages Up to 15 days
- Conditions the study is for
- Neonatal Abstinence Syndrome
- What is being tested?
- Clonidine and Phenobarbital
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2010to Oct 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 15 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- Gestational age < 35 weeks
- Intrauterine growth retardation (birth weight below the 5th percentile)
- Congenital heart disease
- Congenital anomalies
- Medically unstable
- Exposure to Benzodiazepines prenatally
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
NICU @ Baystate Children's Hospital
Springfield, Massachusetts, 01199
About this study
Official title: Comparison of Clonidine Versus Phenobarbital as an Adjunct Therapy for Neonatal Abstinence Syndrome
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.
Read the 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.
- Conditions
- Neonatal Abstinence Syndrome
- Being tested
- Clonidine, Phenobarbital
- Medical subject headings
- Neonatal Abstinence Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClonidineDrug
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.
PhenobarbitalDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| NMS/Clonidine | Experimental | Not described Receives: Drug: Clonidine |
| NMS/Phenobarbital | Active comparator | Not described Receives: Drug: Phenobarbital |
What is being measured
The primary outcome is the main question the study is designed to answer.
Length of Treatment With Neonatal Morphine Sulfate
Measured: subjects were followed for the duration of treatment, up to 3 months
Secondary outcomes (1)
Total Dose of NMS Used
Measured: For the duration of treatment, upto 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2010 (estimated)
- Study startJul 2010
- Primary completionAug 2012
- Study completionOct 2012
Why it stopped: Based on the planned interim analysis results at 50% recruitment, after IRB reviewed the results, further enrollment was stopped.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neonatal Abstinence SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baystate Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rachana Singh, MD, Baystate Medical Center
- Investigators
- Rachana Singh, MD, MS, Principal investigator, Baystate Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01175668
- Sponsor's protocol ID
- BH-10-196
- Status last verified
- Nov 2013
- First submitted
- 14 Jul 2010
- Last updated
- 6 Jan 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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 Dec;33(12):954-9. doi: 10.1038/jp.2013.95. Epub 2013 Aug 15.
PubMed 23949834
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Clonidine Versus Phenobarbital as an Adjunct Therapy for Neonatal Abstinence Syndrome
- ClinicalTrials.gov ID
- NCT01175668
- Acronym / sponsor ID
- BH-10-196
- Conditions
- Neonatal Abstinence Syndrome
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Based on the planned interim analysis results at 50% recruitment, after IRB reviewed the results, further enrollment was stopped.
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Baystate Medical CenterUniversity, hospital or other
- Study start
- Jul 2010
- Primary completion
- Aug 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 5 Aug 2010 (estimated)
- Results
- Posted 6 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NMS/Clonidine | Experimental | Drug: Clonidine |
| NMS/Phenobarbital | Active comparator | Drug: Phenobarbital |
Who may qualify
- Ages
- Up to 15 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (7 listed)
- Gestational age < 35 weeks
- Intrauterine growth retardation (birth weight below the 5th percentile)
- Congenital heart disease
- Congenital anomalies
- Medically unstable
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClonidineThis 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. | Drug | NMS/Clonidine |
| PhenobarbitalInfants 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. | Drug | NMS/Phenobarbital |
Primary outcome
Length of Treatment With Neonatal Morphine Sulfate
Time frame: subjects were followed for the duration of treatment, up to 3 months
1 secondary outcome
Total Dose of NMS Used
Time frame: For the duration of treatment, upto 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23949834Surran 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 Dec;33(12):954-9. doi: 10.1038/jp.2013.95. Epub 2013 Aug 15.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rachana Singh, MD, MS principal investigator
Baystate Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Clonidine and Phenobarbital in people with Neonatal Abstinence Syndrome, run by Baystate Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Length of Treatment With Neonatal Morphine Sulfate (time frame: subjects were followed for the duration of treatment, up to 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01175668, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2014.