Neonatal Abstinence SyndromePhase 2NCT01708707
Comparison of Buprenorphine to Morphine in Treatment of Neonatal Abstinence Syndrome (NAS)
A Phase 2 study testing Buprenorphine and Morphine Sulfate in people with Neonatal Abstinence Syndrome and Neonatal Withdrawal Syndrome, run by Pediatrix at 1 site in United States.
Trial summary
The purpose of the study is to determine whether buprenorphine is a beneficial, safe, cost effective treatment alternative to morphine sulfate in the treatment of Neonatal Abstinence Syndrome (NAS). Read more about this study
- Who is it for?
- Ages Up to 1 year
- Conditions the study is for
- Neonatal Abstinence Syndrome, Neonatal Withdrawal Syndrome
- What is being tested?
- Buprenorphine and Morphine Sulfate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2012to 31 Oct 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 1 year
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants of corrected gestational age ≥37 weeks
- Chronic opioid exposure in utero
- Signs and symptoms of NAS requiring treatment
- 2 consecutive Finnegan scores ≥8 or any single score ≥12
Who cannot join
- Concomitant maternal benzodiazepine or alcohol use 30 days prior to enrollment
- Life-threatening congenital malformations
- Intrauterine growth retardation
- Seizure activity or congenital neurologic abnormalities
- Concomitant neonatal use of Cytochrome P450 inhibitor or inducers prior to treatment
- Inability of mother's consent due to altered mental status or comorbid psychiatric disorder
- Neonatal administration of morphine prior to enrollment into study
Trial locations and contacts
1 site in 1 country.
United States1 site
Banner - University Medical Center Phoenix
Phoenix, Arizona, 85006
About this study
Official title: A Randomized Comparison of Sublingual Buprenorphine to Morphine Sulfate in the Treatment of Neonatal Abstinence Syndrome (NAS)
The purpose of the study is to determine whether buprenorphine is a beneficial, safe, cost effective treatment alternative to morphine sulfate in the treatment of Neonatal Abstinence Syndrome (NAS).
Read the detailed description
Neonatal abstinence syndrome is a condition that affects newborns who are exposed to chronic opioid drugs while they are in a mother's uterus (womb) prior to birth. The current standard of care treatment includes morphine sulfate. Buprenorphine is a drug used in adults to treat narcotic dependence and withdrawal, but has not yet been approved for use in newborns as a treatment alternative for Neonatal Abstinence Syndrome. This investigation is designed to measure if sublingual (under the tongue) buprenorphine is able to reduce hospital length of stay and decrease number of days of drug treatment currently required in treatment of NAS. Another goal will be to understand buprenorphine as a cost effective treatment for NAS.
- Being tested
- Buprenorphine, Morphine Sulfate
- 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.
BuprenorphineDrug
Also called Sublingual buprenorphine, Other Name: Buprenex (buprenorphine), NDC Number: 12496-0757-1, Product Code: 12496-0757
The injectable formulation of buprenorphine (Buprenex; Reckitt Benckiser) will be prepared to a final concentration of 0.075 mg/mL in 100% ethanol and simple syrup USP to create a sublingual preparation.
Infants initial dose: 15.9 µg/kg per day in 3 divided doses with escalation/weaning based upon standardized scoring of NAS symptoms, using standardized Finnegan scoring Maximum dosage: 60 µg/kg per day Duration: Infants will receive buprenorphine until they are successfully weaned off of opioids and no longer show withdrawal symptoms, evidenced by low Finnegan scores. Mean use in other investigations was 24 days.
Morphine SulfateDrug
Also called Oral Morphine Sulfate, Morphine, NDC: 0406-8003-24
Oral Morphine Sulfate Dosage: Morphine Sulfate Oral Solution 100mg/5mL Initially dosed at 0.4mg/kg per day in six daily doses Duration of medication administration dependent upon infant symptoms of neonatal withdrawal, with mean duration of use at Banner Good Samaritan Hospital currently averaging 25 days.
| Study group | Role | What they receive |
|---|---|---|
| Oral morphine sulfate | Active comparator | Oral morphine sulfate 0.4 mg/kg/day morphine every 3-4 hours as needed for Finnegan scores suggestive of Neonatal Abstinence Syndrome Other Name: morphine Receives: Drug: Morphine Sulfate |
| Buprenorphine | Experimental | Sublingual Buprenorphine 15.9 µg/kg per day in 3 divided doses, titrated up or escalated down based upon standardized scoring for neonatal abstinence syndrome Receives: Drug: Buprenorphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hospital length of stay
Number of days of hospital admission
Measured: Up to hospital discharge, an anticipated average of 4 weeks
Secondary outcomes (4)
Number of adverse or serious adverse events
Measured: Up to hospital discharge, with length of stay currently averaging approximately 4 weeks
Cost efficiency of buprenorphine
Cost of buprenorphine as a product of number of days of administration
Measured: At least 48 prior to hospital discharge, with anticipated discharge averaging to be 4 weeks
Withdrawal symptoms
Finnegan methodology to score withdrawal symptoms every four hours of medication administration
Measured: Up to hospital discharge, usually occuring on average 4 weeks
Rescue dosage administration
Number of rescue doses of additional medication
Measured: Up to hospital discharge, anticipating an average of 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2012 (estimated)
- Study startDec 2012
- Primary completionOct 2017
- Study completion31 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pediatrix
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gregory Martin, MD, Principal investigator, Banner University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01708707
- Sponsor's protocol ID
- Banner IRB 01-13-0030
- Status last verified
- Mar 2018
- First submitted
- 25 Apr 2012
- Last updated
- 15 Aug 2018
- Results posted
- No
- 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 15 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Comparison of Sublingual Buprenorphine to Morphine Sulfate in the Treatment of Neonatal Abstinence Syndrome (NAS)
- ClinicalTrials.gov ID
- NCT01708707
- Acronym / sponsor ID
- Banner IRB 01-13-0030
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- PediatrixUniversity, hospital or other
- Study start
- Dec 2012
- Primary completion
- Oct 2017 (actual)
- Study completion
- 31 Oct 2017 (actual)
- First posted
- 17 Oct 2012 (estimated)
- Results
- Not posted in the source record
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 the study is to determine whether buprenorphine is a beneficial, safe, cost effective treatment alternative to morphine sulfate in the treatment of Neonatal Abstinence Syndrome (NAS).
Detailed description
Neonatal abstinence syndrome is a condition that affects newborns who are exposed to chronic opioid drugs while they are in a mother's uterus (womb) prior to birth. The current standard of care treatment includes morphine sulfate. Buprenorphine is a drug used in adults to treat narcotic dependence and withdrawal, but has not yet been approved for use in newborns as a treatment alternative for Neonatal Abstinence Syndrome. This investigation is designed to measure if sublingual (under the tongue) buprenorphine is able to reduce hospital length of stay and decrease number of days of drug treatment currently required in treatment of NAS. Another goal will be to understand buprenorphine as a cost effective treatment for NAS.
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 |
|---|---|---|
| Oral morphine sulfate | Active comparator | Drug: Morphine SulfateOral morphine sulfate 0.4 mg/kg/day morphine every 3-4 hours as needed for Finnegan scores suggestive of Neonatal Abstinence Syndrome Other Name: morphine |
| Buprenorphine | Experimental | Drug: BuprenorphineSublingual Buprenorphine 15.9 µg/kg per day in 3 divided doses, titrated up or escalated down based upon standardized scoring for neonatal abstinence syndrome |
Who may qualify
- Ages
- Up to 1 year
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Infants of corrected gestational age ≥37 weeks
- Chronic opioid exposure in utero
- Signs and symptoms of NAS requiring treatment
- 2 consecutive Finnegan scores ≥8 or any single score ≥12
Key exclusion criteria (7 listed)
- Concomitant maternal benzodiazepine or alcohol use 30 days prior to enrollment
- Life-threatening congenital malformations
- Intrauterine growth retardation
- Seizure activity or congenital neurologic abnormalities
- Concomitant neonatal use of Cytochrome P450 inhibitor or inducers prior to treatment
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 |
|---|---|---|
| BuprenorphineAlso: Sublingual buprenorphine, Other Name: Buprenex (buprenorphine), NDC Number: 12496-0757-1, Product Code: 12496-0757The injectable formulation of buprenorphine (Buprenex; Reckitt Benckiser) will be prepared to a final concentration of 0.075 mg/mL in 100% ethanol and simple syrup USP to create a sublingual preparation. Infants initial dose: 15.9 µg/kg per day in 3 divided doses with escalation/weaning based upon standardized scoring of NAS symptoms, using standardized Finnegan scoring Maximum dosage: 60 µg/kg per day Duration: Infants will receive buprenorphine until they are successfully weaned off of opioids and no longer show withdrawal symptoms, evidenced by low Finnegan scores. Mean use in other investigations was 24 days. | Drug | Buprenorphine |
| Morphine SulfateAlso: Oral Morphine Sulfate, Morphine, NDC: 0406-8003-24Oral Morphine Sulfate Dosage: Morphine Sulfate Oral Solution 100mg/5mL Initially dosed at 0.4mg/kg per day in six daily doses Duration of medication administration dependent upon infant symptoms of neonatal withdrawal, with mean duration of use at Banner Good Samaritan Hospital currently averaging 25 days. | Drug | Oral morphine sulfate |
Primary outcome
Hospital length of stay
Time frame: Up to hospital discharge, an anticipated average of 4 weeks
Number of days of hospital admission
4 secondary outcomes
Number of adverse or serious adverse events
Time frame: Up to hospital discharge, with length of stay currently averaging approximately 4 weeks
Cost efficiency of buprenorphine
Time frame: At least 48 prior to hospital discharge, with anticipated discharge averaging to be 4 weeks
Withdrawal symptoms
Time frame: Up to hospital discharge, usually occuring on average 4 weeks
Rescue dosage administration
Time frame: Up to hospital discharge, anticipating an average of 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2018.
- 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.
Gregory Martin, MD principal investigator
Banner University 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 2 study testing Buprenorphine and Morphine Sulfate in people with Neonatal Abstinence Syndrome and Neonatal Withdrawal Syndrome, run by Pediatrix 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 4 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: finished, as of the sponsor's last update on 15 Aug 2018. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Hospital length of stay (time frame: Up to hospital discharge, an anticipated average of 4 weeks). 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 NCT01708707, 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 15 Aug 2018.