Neonatal Abstinence SyndromePhase 4HOMENOWNCT01723722
Treatment of Neonatal Abstinence Syndrome
A Phase 4 study testing Methadone and Diluted Deodorized Tincture of Opium in people with Neonatal Abstinence Syndrome, run by Eastern Maine Medical Center at 1 site in United States.
Trial summary
This study compares treatment of Neonatal Abstinence Syndrome (NAS) with two different drugs for the difference in the length of treatment. This is a randomized, open-label comparison of phenobarbital and methadone versus phenobarbital and diluted deodorized tincture of opium (dDTO) where phenobarbital is the initial… Read more about this study
- Who is it for?
- Ages 1 day to 6 days
- Conditions the study is for
- Neonatal Abstinence Syndrome
- What is being tested?
- Methadone and Diluted Deodorized Tincture of Opium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Sep 2009
- 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 6 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Evidence of opioid withdrawal clinically as defined by 2 NAS scores >8 or 1 NAS score >12 over a 4 to 8 hour time period, AND
- Gestation >=35 weeks at entry defined by best obstetrical and physical exam criteria, AND
- Medically stable condition, other than in opioid withdrawal, in the opinion of the attending neonatologist, AND EITHER,
- Meconium or urine drug screen positive for opioids on mother or newborn, OR
- Known maternal prescription of opioids for chronic pain management during at least the last trimester of pregnancy, OR
- Known maternal prescription of opioids for treatment of addiction, OR
- Suspected or admitted abuse with opioid drugs
- Infants of mothers with a medical or psychiatric diagnosis will not be excluded, unless the maternal diagnosis precludes informed consent
Who cannot join
- Gestation <35 weeks at entry defined by best obstetrical and physical exam criteria.
- Hypoglycemia, hypomagnesaemia, or hypocalcaemia until corrected.
- Serious medical illness such as sepsis, pneumonia, hyperthyroidism, 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment of Neonatal Abstinence Syndrome: Evaluation of Efficacy of Phenobarbital in Combination With Either Methadone or Diluted Deodorized Tincture of Opium as Stabilizing and Tapering Regiments
This study compares treatment of Neonatal Abstinence Syndrome (NAS) with two different drugs for the difference in the length of treatment. This is a randomized, open-label comparison of phenobarbital and methadone versus phenobarbital and diluted deodorized tincture of opium (dDTO) where phenobarbital is the initial drug used to stabilize neonatal withdrawal.
Read the detailed description
a.Procedures: NAS scoring is currently done on infants meeting the inclusion criteria [IDD 29:070]. NAS scores are initially done every 2 hours for 24 hours and then every 4 hours when awake or before feeding for the duration of observation or treatment.
- NAS scores may indicate more than withdrawal. Conditions such as colic, reflux, or baseline irritability may influence the baseline scores. Decisions made based on the NAS scores should take into account these factors and the baseline for the infant. b.Emergence of symptom, dosing, and initiation of treatment: Withdrawal is defined as at least 2 NAS scores >8 or 1 NAS score >12. Once withdrawal has emerged, the infant will be given: i. Phenobarbital 20 to 30 mg/kg to load divided in up to 3 doses over 24 hours and maintenance phenobarbital should be started at 2.5 mg/kg/dose administered Q 12h, 12 hours after the loading dose is ended. NAS scoring is continued and if scores remain <8 for a minimum of 5 days after starting phenobarbital, the infant is eligible for discharge. ii. If after phenobarbital treatment has been started, at least 2 NAS scores >8 or 1 NAS score >12, then a phenobarbital level will be drawn and a mini-load calculated to reach a level of 30 mg/dl. If withdrawal is not controlled or re-emerges after the mini-load dose, the infant will be randomized to one of the two arms of the study - methadone or dDTO. iii. Twins will be randomized together to the same arm. iv. Randomization will be stratified into mothers on narcotic treatment >3 months and those not in treatment or <3 months. Randomization will be done in blocks of 10 for each stratum.
- For both drugs, the neonatal preparation will be used. vi. The following is a dosing guide for methadone:
- The neonatal concentration is 1 mg/ml of methadone. It is administered orally every 12 hours - standardized eventually to 0900 and 2100.
- For the first 24 hours, doses will be prescribed every 6 hours for 4 doses, using a sliding scale in response to the last NAS score: NAS Score Methadone dose 8-11 0.05 mg/kg/dose 12-15 0.1 mg/kg/dose >16 0.15 mg/kg/dose
- Maximum loading dose of methadone will be 0.15 mg/kg/dose Q 6 hour
- After the first 24 hours of treatment, the total methadone dose will be summed and that dose divided into two doses, given 12 hours apart. Subsequently, PRN doses of 0.05 mg/kg/dose may be given every 6 hours for scores >8 X 2 and added to the next 24 hour's doses, divided every 12 hours, until NAS scores are consistently <8 for 48 hours.
- If at any point the maximum dose of methadone is reached and withdrawal is not controlled, then in the opinion of two neonatologists the patient can be crossed-over to the dDTO arm. vii. The following is a dosing guide for dDTO:
- The neonatal concentration is 1:24 dilution for a concentration of 0.4%, equivalent to 0.4 mg/ml of morphine. It is administered orally every 4 hours - standardized eventually to 0400, 0800, 1200, 1600, 2000, 0000.
- The starting dose is determined by using a sliding scale in response to the last NAS score before starting: NAS Score dDTO dose 8-11 0.1 mg/kg/day 12-15 0.15 mg/kg/day >16 0.2 mg/kg/day For next day, the maintenance dose will return to the previous dose and given in 6 divided doses given Q 4 hours. iv. For either methadone or dDTO, dosing will be held at this level and weaning will be resumed when the infant has NAS scores <8 for 48 hours.
- Holding of doses: Methadone or dDTO will be held for poor feeding, respiratory depression, or somnolence at any time in the protocol.
- Behavioral assessment: Behavioral assessment will be done by two methods. The first by actigraphy and the second by NINS, both during the second week of weaning. The latter will be done prior to a scheduled phenobarbital dose.
- Formula: A 24 kcal/ounce formula should be fed initially using either standard formula or by adding breast milk fortifier. During the weaning period, when weight gain is >30 grams/day for at least 2 days, formula will be changed to 20 kcal/ounce and weight gain monitored. If not sustained, then formula should be changed back to 24 kcal/ounce.
- Conditions
- Neonatal Abstinence Syndrome
- Being tested
- Methadone, Diluted Deodorized Tincture of Opium
- Keywords
- Neonatal Abstinence Syndrome, Methadone, Diluted Deodorized Tincture of Opium, dDTO, 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.
MethadoneDrug
Also called Dolophine
Concentration is 1mg/mL administered every 12 hours given on sliding scale in response to last NAS score.
Diluted Deodorized Tincture of OpiumDrug
Also called Laudanum
Concentration is 1:24 dilution for a concentration of 0.4%
| Study group | Role | What they receive |
|---|---|---|
| 1 (Phenobarbital and Methadone) | Active comparator | The following is a dosing guide for methadone:
1. The neonatal concentration is 1 mg/ml of methadone. It is administered orally every 12 hours.
2. For the first 24 hours, doses will be prescribed every 6 hours using a sliding scale in response to the last NAS score:
NAS Score Methadone dose 8-11 0.05 mg/kg/dose 12-15 0.1 mg/kg/dose
≥16 0.15 mg/kg/dose
3. Maximum dose of methadone will be 0.15 mg/kg/dose.
4. After the first 24 hours of treatment, the total methadone dose will be summed and that dose divided into two doses, given 12 hours apart. For the following 24 hours, additional doses may be given every 6 hours as needed and added to the next 24 hour's doses divided every 12 hours, until NAS scores are consistently <8 for 48 hours.
5. If at any pointthe maximum dose of methadone is reached and withdrawal is not controlled, then in the opinion of two neonatologists the patient can be crossed-over to the dDTO arm. Receives: Drug: Methadone |
| 2 (Phenobarbital and Diluted Deodorized Tincture of Opium) | Active comparator | The following is a dosing guide for dDTO:
1. The neonatal concentration is 1:24 dilution for a concentration of 0.4%, equivalent to 0.4 mg/ml of morphine. It is administered orally every 4 hours.
2. The starting dose will be determined using a sliding scale in response to the last NAS score before starting.
NAS Score Starting dDTO dose 8-11 0.4 mg/kg/day 12-15 0.6 mg/kg/day
≥16 0.8 mg/kg/day
3. The maximum dose of DTO will be 0.8 mg/kg/day.
4. After the first 24 hours of treatment, if the NAS scores are still ≥8, the dose will be increased to the next level.
5. If at any point the maximum dose of methadone is reached and withdrawal is not controlled, then in the opinion of two neonatologists the patient can be crossed-over to the methadone arm. Receives: Drug: Diluted Deodorized Tincture of Opium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Length of Treatment With Opioid Medication
Up to 12 months
Measured: 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 posted8 Nov 2012 (estimated)
- Study startJan 2007
- Primary completionSep 2009
- Study completionSep 2009
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 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 S. Brown, MD, Principal investigator, Eastern Maine Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01723722
- Sponsor's protocol ID
- 07-2-M-107
- Acronym
- HOMENOW
- Status last verified
- Nov 2013
- First submitted
- 27 Jan 2011
- Last updated
- 27 Nov 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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 34231914
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Neonatal Abstinence Syndrome: Evaluation of Efficacy of Phenobarbital in Combination With Either Methadone or Diluted Deodorized Tincture of Opium as Stabilizing and Tapering Regiments
- ClinicalTrials.gov ID
- NCT01723722
- Acronym / sponsor ID
- HOMENOW / 07-2-M-107
- Conditions
- Neonatal Abstinence Syndrome
- Keywords
- Neonatal Abstinence Syndrome, Methadone, Diluted Deodorized Tincture of Opium, dDTO, Phenobarbital
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Eastern Maine Medical CenterUniversity, hospital or other
- Study start
- Jan 2007
- Primary completion
- Sep 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 8 Nov 2012 (estimated)
- Results
- Posted 27 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study compares treatment of Neonatal Abstinence Syndrome (NAS) with two different drugs for the difference in the length of treatment. This is a randomized, open-label comparison of phenobarbital and methadone versus phenobarbital and diluted deodorized tincture of opium (dDTO) where phenobarbital is the initial drug used to stabilize neonatal withdrawal.
Detailed description
a.Procedures: NAS scoring is currently done on infants meeting the inclusion criteria [IDD 29:070]. NAS scores are initially done every 2 hours for 24 hours and then every 4 hours when awake or before feeding for the duration of observation or treatment.
- NAS scores may indicate more than withdrawal. Conditions such as colic, reflux, or baseline irritability may influence the baseline scores. Decisions made based on the NAS scores should take into account these factors and the baseline for the infant. b.Emergence of symptom, dosing, and initiation of treatment: Withdrawal is defined as at least 2 NAS scores >8 or 1 NAS score >12. Once withdrawal has emerged, the infant will be given: i. Phenobarbital 20 to 30 mg/kg to load divided in up to 3 doses over 24 hours and maintenance phenobarbital should be started at 2.5 mg/kg/dose administered Q 12h, 12 hours after the loading dose is ended. NAS scoring is continued and if scores remain <8 for a minimum of 5 days after starting phenobarbital, the infant is eligible for discharge. ii. If after phenobarbital treatment has been started, at least 2 NAS scores >8 or 1 NAS score >12, then a phenobarbital level will be drawn and a mini-load calculated to reach a level of 30 mg/dl. If withdrawal is not controlled or re-emerges after the mini-load dose, the infant will be randomized to one of the two arms of the study - methadone or dDTO. iii. Twins will be randomized together to the same arm. iv. Randomization will be stratified into mothers on narcotic treatment >3 months and those not in treatment or <3 months. Randomization will be done in blocks of 10 for each stratum.
- For both drugs, the neonatal preparation will be used. vi. The following is a dosing guide for methadone:
- The neonatal concentration is 1 mg/ml of methadone. It is administered orally every 12 hours - standardized eventually to 0900 and 2100.
- For the first 24 hours, doses will be prescribed every 6 hours for 4 doses, using a sliding scale in response to the last NAS score: NAS Score Methadone dose 8-11 0.05 mg/kg/dose 12-15 0.1 mg/kg/dose >16 0.15 mg/kg/dose
- Maximum loading dose of methadone will be 0.15 mg/kg/dose Q 6 hour
- After the first 24 hours of treatment, the total methadone dose will be summed and that dose divided into two doses, given 12 hours apart. Subsequently, PRN doses of 0.05 mg/kg/dose may be given every 6 hours for scores >8 X 2 and added to the next 24 hour's doses, divided every 12 hours, until NAS scores are consistently <8 for 48 hours.
- If at any point the maximum dose of methadone is reached and withdrawal is not controlled, then in the opinion of two neonatologists the patient can be crossed-over to the dDTO arm. vii. The following is a dosing guide for dDTO:
- The neonatal concentration is 1:24 dilution for a concentration of 0.4%, equivalent to 0.4 mg/ml of morphine. It is administered orally every 4 hours - standardized eventually to 0400, 0800, 1200, 1600, 2000, 0000.
- The starting dose is determined by using a sliding scale in response to the last NAS score before starting: NAS Score dDTO dose 8-11 0.1 mg/kg/day 12-15 0.15 mg/kg/day >16 0.2 mg/kg/day For next day, the maintenance dose will return to the previous dose and given in 6 divided doses given Q 4 hours. iv. For either methadone or dDTO, dosing will be held at this level and weaning will be resumed when the infant has NAS scores <8 for 48 hours.
- Holding of doses: Methadone or dDTO will be held for poor feeding, respiratory depression, or somnolence at any time in the protocol.
- Behavioral assessment: Behavioral assessment will be done by two methods. The first by actigraphy and the second by NINS, both during the second week of weaning. The latter will be done prior to a scheduled phenobarbital dose.
- Formula: A 24 kcal/ounce formula should be fed initially using either standard formula or by adding breast milk fortifier. During the weaning period, when weight gain is >30 grams/day for at least 2 days, formula will be changed to 20 kcal/ounce and weight gain monitored. If not sustained, then formula should be changed back to 24 kcal/ounce.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 (Phenobarbital and Methadone) | Active comparator | Drug: MethadoneThe following is a dosing guide for methadone: 1. The neonatal concentration is 1 mg/ml of methadone. It is administered orally every 12 hours. 2. For the first 24 hours, doses will be prescribed every 6 hours using a sliding scale in response to the last NAS score: NAS Score Methadone dose 8-11 0.05 mg/kg/dose 12-15 0.1 mg/kg/dose ≥16 0.15 mg/kg/dose 3. Maximum dose of methadone will be 0.15 mg/kg/dose. 4. After the first 24 hours of treatment, the total methadone dose will be summed and that dose divided into two doses, given 12 hours apart. For the following 24 hours, additional doses may be given every 6 hours as needed and added to the next 24 hour's doses divided every 12 hours, until NAS scores are consistently <8 for 48 hours. 5. If at any pointthe maximum dose of methadone is reached and withdrawal is not controlled, then in the opinion of two neonatologists the patient can be crossed-over to the dDTO arm. |
| 2 (Phenobarbital and Diluted Deodorized Tincture of Opium) | Active comparator | Drug: Diluted Deodorized Tincture of OpiumThe following is a dosing guide for dDTO: 1. The neonatal concentration is 1:24 dilution for a concentration of 0.4%, equivalent to 0.4 mg/ml of morphine. It is administered orally every 4 hours. 2. The starting dose will be determined using a sliding scale in response to the last NAS score before starting. NAS Score Starting dDTO dose 8-11 0.4 mg/kg/day 12-15 0.6 mg/kg/day ≥16 0.8 mg/kg/day 3. The maximum dose of DTO will be 0.8 mg/kg/day. 4. After the first 24 hours of treatment, if the NAS scores are still ≥8, the dose will be increased to the next level. 5. If at any point the maximum dose of methadone is reached and withdrawal is not controlled, then in the opinion of two neonatologists the patient can be crossed-over to the methadone arm. |
Who may qualify
- Ages
- 1 day to 6 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Evidence of opioid withdrawal clinically as defined by 2 NAS scores >8 or 1 NAS score >12 over a 4 to 8 hour time period, AND
- Gestation >=35 weeks at entry defined by best obstetrical and physical exam criteria, AND
- Medically stable condition, other than in opioid withdrawal, in the opinion of the attending neonatologist, AND EITHER,
- Meconium or urine drug screen positive for opioids on mother or newborn, OR
- Known maternal prescription of opioids for chronic pain management during at least the last trimester of pregnancy, OR
Key exclusion criteria (4 listed)
- Gestation <35 weeks at entry defined by best obstetrical and physical exam criteria.
- Hypoglycemia, hypomagnesaemia, or hypocalcaemia until corrected.
- Serious medical illness such as sepsis, pneumonia, hyperthyroidism, 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.
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: DolophineConcentration is 1mg/mL administered every 12 hours given on sliding scale in response to last NAS score. | Drug | 1 (Phenobarbital and Methadone) |
| Diluted Deodorized Tincture of OpiumAlso: LaudanumConcentration is 1:24 dilution for a concentration of 0.4% | Drug | 2 (Phenobarbital and Diluted Deodorized Tincture of Opium) |
Primary outcome
Length of Treatment With Opioid Medication
Time frame: Up to 12 months
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 27 Nov 2013.
- 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.
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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 S. Brown, MD principal investigator
Eastern Maine Medical Center
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 Methadone and Diluted Deodorized Tincture of Opium in people with Neonatal Abstinence Syndrome, run by Eastern Maine 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 8 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 27 Nov 2013. 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 27 Nov 2013). 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 Opioid Medication (time frame: Up to 12 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 NCT01723722, 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 27 Nov 2013.