Neonatal Abstinence SyndromePhase 4NASNCT01804075
Comparison Between Methadone and Morphine for Neonatal Opiate Withdrawal
A Phase 4 study testing Methadone and Morphine in people with Neonatal Abstinence Syndrome, run by Eastern Maine Medical Center.
Trial summary
Hypothesis is that the effectiveness of opiate treatment with morphine will result in shorter duration of opiate medication treatment and fewer infants treated with a second drug. Read more about this study
- Who is it for?
- Ages 2 hours to 28 days
- Conditions the study is for
- Neonatal Abstinence Syndrome
- What is being tested?
- Methadone and Morphine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- No sites listed yet
- Study dates
- Jan 2011to Oct 2012
- 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 2 hours to 28 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Evidence of opioid withdrawal clinically defined by at least 2 NAS scores > 8 in an 8 hour time period, AND
- Gestation => 35 weeks at entry defined by best obstetrical and physical exam criteria, AND
- Medically stable condition in the opinion of the attending neonatologist, other than opiate withdrawal, AND
- Mother on opiate replacement treatment therapy - methadone or buprenorphine.
Who cannot join
- Gestation < 35 weeks at entry defined by best obstetrical and physical exam criteria.
- Hypoglycemia, hypomagnesaemia, or hypocalcemia until corrected,
- Serious medical illness such as sepsis, pneumonia, thyroid dysfunction, meningitis, intracranial hemorrhage, perinatal depression, or respiratory failure requiring admission to the NICU.
- Evidence of major congenital anomalies or genetic syndromes that impact the neonatal course
- Mother consistently taking prescribed benzodiazepine at the time of delivery
About this study
Official title: Evaluation of Efficacy of Methadone Versus Morphine for Treatment of Neonatal Abstinence Syndrome (NAS).
Hypothesis is that the effectiveness of opiate treatment with morphine will result in shorter duration of opiate medication treatment and fewer infants treated with a second drug.
Read the detailed description
The purpose is to compare treatment of NAS with two different initial medications with primary outcome of (1) reducing the duration of opiate medication treatment and (2) reducing the number of infants treated with a second medication.
Design is a randomized, blinded comparison. The comparison is between methadone and morphine
Research Design:
- Procedures: NAS scoring is currently done on infants meeting the inclusion criteria. NAS scores are done every 2 hours for 24 hours and then every 4 hours when awake after feeding for the duration of observation and treatment.
- NAS scores may indicate more than withdrawal. Conditions such as colic (hypercaloric formula, transient lactose intolerance), reflux, diaper irritation, prenatal SSRI exposure, and nicotine withdrawal or baseline irritability may influence the variability of scores. Decisions based on the NAS scores should take into account these factors for the infant.
- Emergence of symptom, dosing, and initiation of treatment: Withdrawal significant enough to warrant consideration for treatment is defined as 2 NAS scores >8. Once this threshold has been reached and consent obtained, the infant is randomized to treatment arm, stratified for prenatal exposure to methadone or buprenorphine. Twins will be randomized together to the same arm. The treatment arms are either: i. Methadone (1 mg/mL) or morphine (1 mg/mL) administered orally every 4 hours. The following is a dosing guide:
NAS Score Methadone or Morphine 8-12 0.05 mg/kg/dose >13 0.1 mg/kg/dose
- Maximum dose of methadone or morphine will be 0.2 mg/kg/dose. (NeoFax)
- Additional doses, 0.05 mg/kg, may be given every 12 hours as needed and added to the next 24 hour's doses divided every 4 hours, until NAS scores are consistently <8 for 48 hours.
- If the maximum dose of methadone or morphine is reached and if withdrawal is not controlled, the infant will be started on clonazepam (0.005 mg/kg/dose q 12h) per current treatment.
- Tapering medications: When the infant has NAS scores consistently <8 for 36 hours: i.The taper will be on a daily basis of 10% of the final maintenance dose. Dosages will be decreased in a measured amount to maintain NAS scores <8. After the last dose, there will be a 24 to 36 hour observation period. d.Non-tolerance of tapering: Non-tolerance of tapering is defined as 2 NAS scores >8 during the 12 hour period prior to the next taper dose: i.The tapering should be stopped at the current level. ii.If necessary, an extra dose of methadone or morphine can be given and added to the next day's dose divided into 6 doses. If withdrawal re-emerges after this dose (2 NAS scores >8), then the maintenance dose should be increased back to the last level; an extra dose may be given up to 4 to 5 hours after the previous dose. iii. If an extra dose is not given, the wean schedule can be resumed after 24 hours of NAS scores <8; when dosing is resumed, the frequency should be changed to every 4 hours with the same total daily dose.
- Holding of doses: Methadone or morphine will be held for poor feeding, respiratory depression, or somnolence at any time in the protocol.
- Conditions
- Neonatal Abstinence Syndrome
- Being tested
- Methadone, Morphine
- Keywords
- NAS, NICU, EMMC
- 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.
MethadoneDrug
Also called see arm/group descriptions
To compare the duration of opiate medication treatment for babies on methadone versus those on morphine.
MorphineDrug
Also called see arm/group descriptions
To compare the duration of opiate medication treatment for babies on methadone versus those on morphine.
| Study group | Role | What they receive |
|---|---|---|
| methadone | Active comparator | Methadone (1 mg/mL) administered orally every 4 hours. The following is a dosing guide:
NAS Score Methadone 8-12 0.05 mg/kg/dose >=13 0.1 mg/kg/dose
1. Maximum dose of methadone will be 0.2 mg/kg/dose. (NeoFax)
2. Additional doses, 0.05 mg/kg, may be given every 4 hours as needed and added to the next 24 hour's doses divided every 4 hours, until NAS scores are consistently <8 for 48 hours.
3. If the maximum dose of methadone is reached and if withdrawal is not controlled, the infant will be started on clonazepam (0.005 mg/kg/dose q 12h) per current treatment. Receives: Drug: Methadone |
| morphine | Active comparator | Morphine (1 mg/mL) administered orally every 4 hours. The following is a dosing guide:
NAS Score Morphine 8-12 0.05 mg/kg/dose >=13 0.1 mg/kg/dose
1. Maximum dose of morphine will be 0.2 mg/kg/dose. (NeoFax)
2. Additional doses, 0.05 mg/kg, may be given every 4 hours as needed and added to the next 24 hour's doses divided every 6 hours, until NAS scores are consistently <8 for 48 hours.
3. If the maximum dose of morphine is reached and if withdrawal is not controlled, the infant will be started on clonazepam (0.005 mg/kg/dose q 12h) per current treatment. Receives: Drug: Morphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days of Treatment With Opioid Medication
The length of time in days that the treatment opioid was used on a measured taper to ameliorate withdrawal signs
Measured: From date of randomization until the date of last opioid dose or date of death from any cause, whichever came first, assessed up to 12 months
Secondary outcomes (1)
Second Drug for Withdrawal
Number of infants treated with a second drug to treat their withdrawal
Measured: From date of randomization until the date of last opioid dose or date of death from any cause or date of discharge, whichever came first, assessed up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2013 (estimated)
- Study startJan 2011
- Primary completionOct 2012
- Study completionOct 2012
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.
- 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
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eastern Maine Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mark S Brown, MD, Eastern Maine Medical Center
- Investigators
- Mark Brown, MD, Principal investigator, Eastern Maine Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01804075
- Sponsor's protocol ID
- 10-1-M-185
- Acronym
- NAS
- Status last verified
- Aug 2017
- First submitted
- 6 Nov 2012
- Last updated
- 28 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Efficacy of Methadone Versus Morphine for Treatment of Neonatal Abstinence Syndrome (NAS).
- ClinicalTrials.gov ID
- NCT01804075
- Acronym / sponsor ID
- NAS / 10-1-M-185
- Conditions
- Neonatal Abstinence Syndrome
- Keywords
- NAS, NICU, EMMC
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Eastern Maine Medical CenterUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 5 Mar 2013 (estimated)
- Results
- Posted 30 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hypothesis is that the effectiveness of opiate treatment with morphine will result in shorter duration of opiate medication treatment and fewer infants treated with a second drug.
Detailed description
The purpose is to compare treatment of NAS with two different initial medications with primary outcome of (1) reducing the duration of opiate medication treatment and (2) reducing the number of infants treated with a second medication.
Design is a randomized, blinded comparison. The comparison is between methadone and morphine
Research Design:
- Procedures: NAS scoring is currently done on infants meeting the inclusion criteria. NAS scores are done every 2 hours for 24 hours and then every 4 hours when awake after feeding for the duration of observation and treatment.
- NAS scores may indicate more than withdrawal. Conditions such as colic (hypercaloric formula, transient lactose intolerance), reflux, diaper irritation, prenatal SSRI exposure, and nicotine withdrawal or baseline irritability may influence the variability of scores. Decisions based on the NAS scores should take into account these factors for the infant.
- Emergence of symptom, dosing, and initiation of treatment: Withdrawal significant enough to warrant consideration for treatment is defined as 2 NAS scores >8. Once this threshold has been reached and consent obtained, the infant is randomized to treatment arm, stratified for prenatal exposure to methadone or buprenorphine. Twins will be randomized together to the same arm. The treatment arms are either: i. Methadone (1 mg/mL) or morphine (1 mg/mL) administered orally every 4 hours. The following is a dosing guide:
NAS Score Methadone or Morphine 8-12 0.05 mg/kg/dose >13 0.1 mg/kg/dose
- Maximum dose of methadone or morphine will be 0.2 mg/kg/dose. (NeoFax)
- Additional doses, 0.05 mg/kg, may be given every 12 hours as needed and added to the next 24 hour's doses divided every 4 hours, until NAS scores are consistently <8 for 48 hours.
- If the maximum dose of methadone or morphine is reached and if withdrawal is not controlled, the infant will be started on clonazepam (0.005 mg/kg/dose q 12h) per current treatment.
- Tapering medications: When the infant has NAS scores consistently <8 for 36 hours: i.The taper will be on a daily basis of 10% of the final maintenance dose. Dosages will be decreased in a measured amount to maintain NAS scores <8. After the last dose, there will be a 24 to 36 hour observation period. d.Non-tolerance of tapering: Non-tolerance of tapering is defined as 2 NAS scores >8 during the 12 hour period prior to the next taper dose: i.The tapering should be stopped at the current level. ii.If necessary, an extra dose of methadone or morphine can be given and added to the next day's dose divided into 6 doses. If withdrawal re-emerges after this dose (2 NAS scores >8), then the maintenance dose should be increased back to the last level; an extra dose may be given up to 4 to 5 hours after the previous dose. iii. If an extra dose is not given, the wean schedule can be resumed after 24 hours of NAS scores <8; when dosing is resumed, the frequency should be changed to every 4 hours with the same total daily dose.
- Holding of doses: Methadone or morphine will be held for poor feeding, respiratory depression, or somnolence at any time in the protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| methadone | Active comparator | Drug: MethadoneMethadone (1 mg/mL) administered orally every 4 hours. The following is a dosing guide: NAS Score Methadone 8-12 0.05 mg/kg/dose >=13 0.1 mg/kg/dose 1. Maximum dose of methadone will be 0.2 mg/kg/dose. (NeoFax) 2. Additional doses, 0.05 mg/kg, may be given every 4 hours as needed and added to the next 24 hour's doses divided every 4 hours, until NAS scores are consistently <8 for 48 hours. 3. If the maximum dose of methadone is reached and if withdrawal is not controlled, the infant will be started on clonazepam (0.005 mg/kg/dose q 12h) per current treatment. |
| morphine | Active comparator | Drug: MorphineMorphine (1 mg/mL) administered orally every 4 hours. The following is a dosing guide: NAS Score Morphine 8-12 0.05 mg/kg/dose >=13 0.1 mg/kg/dose 1. Maximum dose of morphine will be 0.2 mg/kg/dose. (NeoFax) 2. Additional doses, 0.05 mg/kg, may be given every 4 hours as needed and added to the next 24 hour's doses divided every 6 hours, until NAS scores are consistently <8 for 48 hours. 3. If the maximum dose of morphine is reached and if withdrawal is not controlled, the infant will be started on clonazepam (0.005 mg/kg/dose q 12h) per current treatment. |
Who may qualify
- Ages
- 2 hours to 28 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Evidence of opioid withdrawal clinically defined by at least 2 NAS scores > 8 in an 8 hour time period, AND
- Gestation => 35 weeks at entry defined by best obstetrical and physical exam criteria, AND
- Medically stable condition in the opinion of the attending neonatologist, other than opiate withdrawal, AND
- Mother on opiate replacement treatment therapy - methadone or buprenorphine.
Key exclusion criteria (5 listed)
- Gestation < 35 weeks at entry defined by best obstetrical and physical exam criteria.
- Hypoglycemia, hypomagnesaemia, or hypocalcemia until corrected,
- Serious medical illness such as sepsis, pneumonia, thyroid dysfunction, meningitis, intracranial hemorrhage, perinatal depression, or respiratory failure requiring admission to the NICU.
- Evidence of major congenital anomalies or genetic syndromes that impact the neonatal course
- Mother consistently taking prescribed benzodiazepine at the time of delivery
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 |
|---|---|---|
| MethadoneAlso: see arm/group descriptionsTo compare the duration of opiate medication treatment for babies on methadone versus those on morphine. | Drug | methadone |
| MorphineAlso: see arm/group descriptionsTo compare the duration of opiate medication treatment for babies on methadone versus those on morphine. | Drug | morphine |
Primary outcome
Days of Treatment With Opioid Medication
Time frame: From date of randomization until the date of last opioid dose or date of death from any cause, whichever came first, assessed up to 12 months
The length of time in days that the treatment opioid was used on a measured taper to ameliorate withdrawal signs
1 secondary outcome
Second Drug for Withdrawal
Time frame: From date of randomization until the date of last opioid dose or date of death from any cause or date of discharge, whichever came first, assessed up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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An Intervention Mapping Approach to Closing the Gap in Maternal OUD and Infant NAS Care (SUPPORT)
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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.
Mark Brown, MD principal investigator
Eastern Maine Medical Center
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methadone and Morphine in people with Neonatal Abstinence Syndrome, run by Eastern Maine Medical Center.
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 4 inclusion and 5 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 28 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
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 30 Aug 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?
Days of Treatment With Opioid Medication (time frame: From date of randomization until the date of last opioid dose or date of death from any cause, whichever came first, assessed up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Sep 2017.