Neonatal Abstinence SyndromePhase 4NASNCT01734551
NAS Treatment - Opiate Versus Non-Opiate
A Phase 4 study testing Morphine and Clonidine in people with Neonatal Abstinence Syndrome, run by Henrietta Bada at 1 site in United States.
Trial summary
The purpose of this study is to compare two different medicines to treat babies with opiate withdrawal. The treatment medicines are morphine, which is an opiate, and clonidine, a non-opiate. Morphine is a narcotic medicine, with is included in most pain killers. Read more about this study
- Who is it for?
- Ages 1 day to 7 days
- Conditions the study is for
- Neonatal Abstinence Syndrome
- What is being tested?
- Morphine and Clonidine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2011to Dec 2014
- Phase
- Phase 4
- 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 1 day to 7 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Admitted to Neonatal Intensive Care Unit (NICU)- Gestational age (GA) >or= 35 wks
- Known prenatal opiate exposure (maternal history, positive opiate screen, positive neonatal urine or meconium screen)
- Symptomatic with Finnegan Neonatal Abstinence Scores meeting NICU protocol for treatment
Who cannot join
- Seizures
- Major congenital malformations
- Unlikely to survive
- Parents not able to understand English
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kentucky Medical Center
Lexington, Kentucky, 40536
About this study
Official title: Pharmacological Treatment of Neonatal Abstinence Syndrome: Opiate Versus Non-Opiate
The purpose of this study is to compare two different medicines to treat babies with opiate withdrawal. The treatment medicines are morphine, which is an opiate, and clonidine, a non-opiate. Morphine is a narcotic medicine, with is included in most pain killers. Clonidine is another drug, but is different from morphine. It is also used for babies, and even adults for withdrawal symptoms. Both drugs are effective, but the purpose of this study is to see if one may be better than the other.
Read the detailed description
Withdrawal from drugs, called Neonatal abstinence syndrome (NAS), is a group of symptoms that occurs to babies whose mother took or used drugs (prescription, addicting, illegal, pain pills, or drugs for addiction treatment) during pregnancy. Medicines the mother takes while pregnant, the baby also takes. Babies may experience withdrawal after delivery, and may need treatment. There are different ways to treat babies with withdrawal - about 50% of doctors use morphine, an opiate, to treat these babies, the rest uses other drugs, like clonidine and phenobarbitol.
- Conditions
- Neonatal Abstinence Syndrome
- Being tested
- Morphine, Clonidine
- Keywords
- Prenatal opiate exposure, neonatal withdrawal, Pharmacologic treatment
- 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.
MorphineDrug
Also called Morphine sulfate
Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day.
Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is <0.1mg/kg/day, may discontinue.
ClonidineDrug
Also called clonidine hydrochloride
Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.
| Study group | Role | What they receive |
|---|---|---|
| Morphine | Active comparator | Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. Receives: Drug: Morphine |
| Clonidine | Active comparator | Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. Receives: Drug: Clonidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Finnegan Neonatal Abstinence Scoring System
Mean of total Finnegan Scores obtained every 3 hours on days 2, 7, and 14 following start of treatment; A score is a number representing the total score or sum from 21 items or symptoms or manifestations of opiate withdrawal in newborn infants. The total score ranges from 0 to 43. Reference: 1. Finnegan LP, Connaughton JF, Jr., Kron RE, et al. Neonatal abstinence syndrome: assessment and management. Addict Dis 1975;2(1-2):141-58. Although normal newborn may manifest mild symptoms that will give scores in the range of 0 to 7. A score of 8 consecutively obtained times 3 indicate that infant will benefit from treatment, in this study morphine or clonidine. A decrease in scores especially to less than 8 is suggestive of a good response to treatment.
Measured: 14 days
Duration of Treatment
Total number days of treatment
Measured: 120 days
Secondary outcomes (2)
Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)
The summary scores from the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) give a measure of infant neurobehavior in the following areas (score range): habituation (1-9), regulation (2.20-7.50), attention (1.29 -8.4), Handling (0 - 1), quality of movement (1.20 - 6.20), Non-optimal reflexes (0-12), Asymmetric reflexes (0-7), arousal (2.43 - 6.67), hypertonicity (0- 8), hypotonicity (0 - 5.0), excitability (0-11), lethargy (0 - 11.0). and stress/abstinence (0. - 0.57). A higher score for each item means a higher level of the construct. For example, a higher score for hypertonicity means the infant is more hypertonic and higher score on hypotonicity means the infant is more hypotonic. No cut-off score published for normal or abnormal behavioral performance. Reference: Lester BM et al. Summary Statistics of Neonatal Intensive Care Unit Network Neurobehavioral Scale Scores From the Maternal Lifestyle Study: A Quasinormative Sample, in Pediatrics 2004; 113,668.
Measured: 5-10 days after treatment starts
Bayley Scales of Infant and Toddler Development Third Edition
Scores obtained Bayley Scales of Infant and Toddler Development Third Edition in the developmental domains of motor, cognitive, and language. This tool for measures of motor, cognitive and language development is a series of standardized measurements and for each domain, the standardized scores have a mean of 100 and standard deviation of 15. Scores below 1 standard deviation (= or less than 84) is considered below normal. Scores above 1 standard deviation (over 115) represent higher than normal functioning in each domain The score for each domain (motor, cognitive, and language functioning) represents the full-scale score
Measured: 1 year of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2012 (estimated)
- Study startSep 2011
- Primary completionDec 2014
- Study completionDec 2014
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 (2)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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Henrietta Bada
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Henrietta Bada, University of Kentucky
- Investigators
- Henrietta S Bada, MD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01734551
- Sponsor's protocol ID
- 11-0534
- Acronym
- NAS
- Status last verified
- Aug 2017
- First submitted
- 21 Nov 2012
- Last updated
- 12 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Zankl A, Martin J, Davey JG, Osborn DA. Opioid treatment for opioid withdrawal in newborn infants. Cochrane Database Syst Rev. 2021 Jul 7;7(7):CD002059. doi: 10.1002/14651858.CD002059.pub4.
PubMed 34231914Bada HS, Sithisarn T, Gibson J, Garlitz K, Caldwell R, Capilouto G, Li Y, Leggas M, Breheny P. Morphine versus clonidine for neonatal abstinence syndrome. Pediatrics. 2015 Feb;135(2):e383-91. doi: 10.1542/peds.2014-2377.
PubMed 25624389
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacological Treatment of Neonatal Abstinence Syndrome: Opiate Versus Non-Opiate
- ClinicalTrials.gov ID
- NCT01734551
- Acronym / sponsor ID
- NAS / 11-0534
- Conditions
- Neonatal Abstinence Syndrome
- Keywords
- Prenatal opiate exposure, neonatal withdrawal, Pharmacologic treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Henrietta BadaUniversity, hospital or other
- Study start
- Sep 2011
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 27 Nov 2012 (estimated)
- Results
- Posted 12 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare two different medicines to treat babies with opiate withdrawal. The treatment medicines are morphine, which is an opiate, and clonidine, a non-opiate. Morphine is a narcotic medicine, with is included in most pain killers. Clonidine is another drug, but is different from morphine. It is also used for babies, and even adults for withdrawal symptoms. Both drugs are effective, but the purpose of this study is to see if one may be better than the other.
Detailed description
Withdrawal from drugs, called Neonatal abstinence syndrome (NAS), is a group of symptoms that occurs to babies whose mother took or used drugs (prescription, addicting, illegal, pain pills, or drugs for addiction treatment) during pregnancy. Medicines the mother takes while pregnant, the baby also takes. Babies may experience withdrawal after delivery, and may need treatment. There are different ways to treat babies with withdrawal - about 50% of doctors use morphine, an opiate, to treat these babies, the rest uses other drugs, like clonidine and phenobarbitol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Morphine | Active comparator | Drug: MorphineInitial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. |
| Clonidine | Active comparator | Drug: ClonidineDose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. |
Who may qualify
- Ages
- 1 day to 7 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Admitted to Neonatal Intensive Care Unit (NICU)- Gestational age (GA) >or= 35 wks
- Known prenatal opiate exposure (maternal history, positive opiate screen, positive neonatal urine or meconium screen)
- Symptomatic with Finnegan Neonatal Abstinence Scores meeting NICU protocol for treatment
Key exclusion criteria (4 listed)
- Seizures
- Major congenital malformations
- Unlikely to survive
- Parents not able to understand English
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 |
|---|---|---|
| MorphineAlso: Morphine sulfateStart at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day. Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is <0.1mg/kg/day, may discontinue. | Drug | Morphine |
| ClonidineAlso: clonidine hydrochlorideInitial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing. | Drug | Clonidine |
Primary outcome
Finnegan Neonatal Abstinence Scoring System
Time frame: 14 days
Mean of total Finnegan Scores obtained every 3 hours on days 2, 7, and 14 following start of treatment; A score is a number representing the total score or sum from 21 items or symptoms or manifestations of opiate withdrawal in newborn infants. The total score ranges from 0 to 43. Reference: 1. Finnegan LP, Connaughton JF, Jr., Kron RE, et al. Neonatal abstinence syndrome: assessment and management. Addict Dis 1975;2(1-2):141-58. Although normal newborn may manifest mild symptoms that will give scores in the range of 0 to 7. A score of 8 consecutively obtained times 3 indicate that infant will benefit from treatment, in this study morphine or clonidine. A decrease in scores especially to less than 8 is suggestive of a good response to treatment.
Duration of Treatment
Time frame: 120 days
Total number days of treatment
2 secondary outcomes
Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)
Time frame: 5-10 days after treatment starts
Bayley Scales of Infant and Toddler Development Third Edition
Time frame: 1 year of life
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34231914Zankl A, Martin J, Davey JG, Osborn DA. Opioid treatment for opioid withdrawal in newborn infants. Cochrane Database Syst Rev. 2021 Jul 7;7(7):CD002059. doi: 10.1002/14651858.CD002059.pub4.
- Derived from this study: PubMed 25624389Bada HS, Sithisarn T, Gibson J, Garlitz K, Caldwell R, Capilouto G, Li Y, Leggas M, Breheny P. Morphine versus clonidine for neonatal abstinence syndrome. Pediatrics. 2015 Feb;135(2):e383-91. doi: 10.1542/peds.2014-2377.
- Individual participant dataSharing planned: No
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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.
Henrietta S Bada, MD principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Morphine and Clonidine in people with Neonatal Abstinence Syndrome, run by Henrietta Bada 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 4 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: finished, as of the sponsor's last update on 12 Sep 2017. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Sep 2017). 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?
Finnegan Neonatal Abstinence Scoring System (time frame: 14 days). The study lists 2 primary outcomes in all. 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 NCT01734551, which also lists 2 linked publications.
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 12 Sep 2017.