Narcotic AddictionPhase 2AIM2NASNCT01965704
Can Ondansetron Prevent Neonatal Abstinence Syndrome (NAS) in Babies Born to Narcotic-dependent Women
A Phase 2 study testing Ondansetron in people with Narcotic Addiction and Neonatal Abstinence Syndrome, run by Stanford University at 8 sites in United States.
Trial summary
The Investigators hope to learn if they can prevent or lessen the symptoms of neonatal abstinence syndrome (NAS) in babies born to narcotic-dependent mothers by using the drug ondansetron in the mothers prior to delivery and their babies after delivery. Read more about this study
- Who is it for?
- Ages Up to 45 years
- Conditions the study is for
- Narcotic Addiction, Neonatal Abstinence Syndrome
- What is being tested?
- Ondansetron
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 196 participants
- Where
- 8 sitesUnited States
- Study dates
- 9 Sep 2014to 16 Sep 2020
- Phase
- Phase 2
- 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 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- adult female, opioid-dependent for at least 3 weeks prior to delivery.
- adult female, otherwise healthy.
- adult female, age 18-45 years inclusive.
- adult female, signed consent to participate for self and neonate (maternal subject may decide not to receive the study drug but her neonate can still be included in the study).
- neonate, gestational age 37 weeks through 41 weeks and 6 days at birth.
- neonate, corrected QT interval (QTc) from 12-lead electrocardiogram (ECG) less than 480 milliseconds (ms).
Who cannot join
- adult female, any condition that, in the opinion of the investigator, would compromise the health of the participant (both mother and fetus) or the integrity of the data.
- adult female, known allergy to study drug (ondansetron).
- adult female, screening 12-lead ECG, if done, showing prolonged QTc will stop the mother from receiving any study drug but her neonate can still be included in the study.
- adult female, not dependent on opioids for at least 3 weeks prior to delivery.
- adult female, generally not healthy.
- adult female, age 17 years or less or 46 years of age and older.
Show all 9Show fewer
- adult female and neonate, the maternal ingestion or administration of ondansetron within 24 hours prior to delivery, for reasons other than study purposes, will exclude the mother and the neonate.
- neonate, preterm or post-term gestational age at delivery.
- neonate, QTc showing results greater than or equal to 480ms on any 12-lead ECG post delivery will stop the dosing of the study drug, but safety follow up will be done if the mother or baby received at least one dose of study drug.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
University of Louisville
Louisville, Kentucky, 40292
University of Tennessee Health Science Center
Memphis, Tennessee, 38163
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
The University of Utah
Salt Lake City, Utah, 84112
UCSF, San Francisco General Hospital
San Francisco, California, 94110
Santa Clara Valley Medical Center
San Jose, California, 95128
Stanford University Medical Center
Stanford, California, 94305
About this study
Official title: AIM 2- Prevention of Neonatal Abstinence Syndrome
The Investigators hope to learn if they can prevent or lessen the symptoms of neonatal abstinence syndrome (NAS) in babies born to narcotic-dependent mothers by using the drug ondansetron in the mothers prior to delivery and their babies after delivery.
The study is a randomized, double-blind, placebo-controlled study with one half the mother-baby pairs to receive ondansetron and the other half of the mother-baby pairs to receive placebo. The pregnant narcotic-dependent mothers will receive an intravenous dose of study medication prior to delivery; the neonates, after their birth, will receive the same study medication the mother received every 24 hours for up to 5 days.
The Investigators will follow up with the mother-baby pairs for 10 days after study drug has stopped and one last follow up, about 30 days after stopping study drug, to learn if the baby had any symptoms of NAS in that time period.
Read the detailed description
All neonates will have a screening 12-lead EKG prior to their first dose of study medication to determine if QTc prolongation is present. A repeat 12-lead EKG will be done after each dose of study medication, approximately 2-5 hours post dose; if a neonate has prolonged QTc the study drug will be stopped.
Investigators may obtain up to 9 pharmacokinetic (PK) blood samples from the neonates over 5 days when standard of care blood samples are drawn. These samples will consist of 1 to 2 drops of blood collected on filter paper and sent to Stanford for PK analysis.
The modified Finnegan scoring system will be used to evaluate neonates for symptoms of NAS at each site and it is considered standard-of-care for babies at risk of NAS. Morphine will be the first treatment choice before other treatment medication choices (opioid or non-opioid) for NAS symptoms. Each site involved has established guidelines for starting, advancing and weaning treatment for NAS. Any medication used to treat NAS will be recorded.
Interim analysis: will be performed after the first 20 pregnant women and their neonates have been enrolled and dosed with study drug. (Interim Analysis was done on first 21 mother/baby pairs in May 2016).
To protect the confidentiality of the patients (study subjects), the lead site, Stanford University, received a Certificate of Confidentiality from the NIH.
- Conditions
- Narcotic Addiction, Neonatal Abstinence Syndrome
- Being tested
- Ondansetron, Placebo
- Keywords
- Narcotic addiction during pregnancy, Neonatal abstinence syndrome, NAS
- Medical subject headings
- Narcotic-Related Disorders, Neonatal Abstinence Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OndansetronDrug
Also called Zofran
Pregnant women may receive a second dose of IV ondansetron if they have not delivered within 4 hours of receiving the IV study medication. 50% of the 90 mother/baby pairs will receive ondansetron; the baby will always get the same study medication as the mother.
PlaceboDrug
Also called IV Normal saline; oral simple syrup
All doses of placebo, whether IV or oral, will mimic the same volume as the ondansetron group to maintain the blind. Pregnant women may receive a second dose of IV placebo if they have not delivered within 4 hours of being given the IV study medication. 50% of the 90 mother/baby pairs will receive placebo; the baby will always receive the same study medication as the mother.
| Study group | Role | What they receive |
|---|---|---|
| Ondansetron | Experimental | Pregnant Women: ondansetron 8mg intravenously (IV) within 4 hours of delivery. Neonates: ondansetron 0.07 mg/kg given orally every 24 hours starting 4-8 hours after delivery, for up to 5 days (if IV line available in neonate, ondansetron 0.04 mg/kg IV every 24 hours for up to 5 days). Receives: Drug: Ondansetron |
| Placebo | Placebo comparator | Pregnant Women: placebo given intravenously prior to delivery (volume to mimic the IV volume of the ondansetron group).
Neonates: placebo given orally every 24 hours, starting 4-8 hours after delivery, for up to 5 days with volume to mimic the oral volume of the ondansetron group (if IV line available, placebo may be given IV). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Neonatal Abstinence Syndrome
The incidence of neonatal abstinence syndrome (NAS) measured as the number of neonates who need for morphine treatment for the symptoms of neonatal opioid withdrawal syndrome (NOWS) while the neonates received study medication and for the 30 days after stopping the study medication.
Measured: 35 days
Secondary outcomes (3)
Length of Hospital Stay
Severity of NAS will be measured by neonates' length of hospital stay (birth to discharge). Length of stay was calculated with 1) no maximum length, and 2) maximum length of stay capped at 15 days. All participants were included in both analyses.
Measured: At Day 15 and up to 64 days
Total Dose of Narcotic Required to Treat the Symptoms of NAS
Median dose of morphine required by neonates within 15 days of delivery.
Measured: 15 days
Number of Participants Requiring Adjunctive Medication to Treat NOWS
Number of neonates requiring treatment with phenobarbital or clonidine.
Measured: 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2013 (estimated)
- Study start9 Sep 2014
- Primary completion3 Sep 2020
- Study completion16 Sep 2020
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 Narcotic AddictionStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 196 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Santa Clara Valley Medical Center, Thomas Jefferson University
- Responsible party
- Principal investigator, David R. Drover, Stanford University
- Investigators
- David R Drover, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01965704
- Sponsor's protocol ID
- Aim 2_RO1-HD-070795-01A1
- Other IDs
- NAS2
- Acronym
- AIM2NAS
- Status last verified
- Jun 2022
- First submitted
- 15 Oct 2013
- Last updated
- 7 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- Individual data sharing
- No: We will not share any individual participant data with other researchers.
Publications
Peltz G, Jansson LM, Adeniyi-Jones S, Cohane C, Drover D, Shafer S, Wang M, Wu M, Govindaswami B, Jegatheesan P, Argani C, Khan S, Kraft WK. Ondansetron to reduce neonatal opioid withdrawal severity a randomized clinical trial. J Perinatol. 2023 Mar;43(3):271-276. doi: 10.1038/s41372-022-01487-2. Epub 2022 Aug 27.
PubMed 36030327
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AIM 2- Prevention of Neonatal Abstinence Syndrome
- ClinicalTrials.gov ID
- NCT01965704
- Acronym / sponsor ID
- AIM2NAS / Aim 2_RO1-HD-070795-01A1
- Conditions
- Narcotic Addiction, Neonatal Abstinence Syndrome
- Keywords
- Narcotic addiction during pregnancy, Neonatal abstinence syndrome, NAS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 196 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Santa Clara Valley Medical Center, Thomas Jefferson University
- Study start
- 9 Sep 2014 (actual)
- Primary completion
- 3 Sep 2020 (actual)
- Study completion
- 16 Sep 2020 (actual)
- First posted
- 18 Oct 2013 (estimated)
- Results
- Posted 10 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Investigators hope to learn if they can prevent or lessen the symptoms of neonatal abstinence syndrome (NAS) in babies born to narcotic-dependent mothers by using the drug ondansetron in the mothers prior to delivery and their babies after delivery.
The study is a randomized, double-blind, placebo-controlled study with one half the mother-baby pairs to receive ondansetron and the other half of the mother-baby pairs to receive placebo. The pregnant narcotic-dependent mothers will receive an intravenous dose of study medication prior to delivery; the neonates, after their birth, will receive the same study medication the mother received every 24 hours for up to 5 days.
The Investigators will follow up with the mother-baby pairs for 10 days after study drug has stopped and one last follow up, about 30 days after stopping study drug, to learn if the baby had any symptoms of NAS in that time period.
Detailed description
All neonates will have a screening 12-lead EKG prior to their first dose of study medication to determine if QTc prolongation is present. A repeat 12-lead EKG will be done after each dose of study medication, approximately 2-5 hours post dose; if a neonate has prolonged QTc the study drug will be stopped.
Investigators may obtain up to 9 pharmacokinetic (PK) blood samples from the neonates over 5 days when standard of care blood samples are drawn. These samples will consist of 1 to 2 drops of blood collected on filter paper and sent to Stanford for PK analysis.
The modified Finnegan scoring system will be used to evaluate neonates for symptoms of NAS at each site and it is considered standard-of-care for babies at risk of NAS. Morphine will be the first treatment choice before other treatment medication choices (opioid or non-opioid) for NAS symptoms. Each site involved has established guidelines for starting, advancing and weaning treatment for NAS. Any medication used to treat NAS will be recorded.
Interim analysis: will be performed after the first 20 pregnant women and their neonates have been enrolled and dosed with study drug. (Interim Analysis was done on first 21 mother/baby pairs in May 2016).
To protect the confidentiality of the patients (study subjects), the lead site, Stanford University, received a Certificate of Confidentiality from the NIH.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ondansetron | Experimental | Drug: OndansetronPregnant Women: ondansetron 8mg intravenously (IV) within 4 hours of delivery. Neonates: ondansetron 0.07 mg/kg given orally every 24 hours starting 4-8 hours after delivery, for up to 5 days (if IV line available in neonate, ondansetron 0.04 mg/kg IV every 24 hours for up to 5 days). |
| Placebo | Placebo comparator | Drug: PlaceboPregnant Women: placebo given intravenously prior to delivery (volume to mimic the IV volume of the ondansetron group). Neonates: placebo given orally every 24 hours, starting 4-8 hours after delivery, for up to 5 days with volume to mimic the oral volume of the ondansetron group (if IV line available, placebo may be given IV). |
Who may qualify
- Ages
- Up to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- adult female, opioid-dependent for at least 3 weeks prior to delivery.
- adult female, otherwise healthy.
- adult female, age 18-45 years inclusive.
- adult female, signed consent to participate for self and neonate (maternal subject may decide not to receive the study drug but her neonate can still be included in the study).
- neonate, gestational age 37 weeks through 41 weeks and 6 days at birth.
Key exclusion criteria (9 listed)
- adult female, any condition that, in the opinion of the investigator, would compromise the health of the participant (both mother and fetus) or the integrity of the data.
- adult female, known allergy to study drug (ondansetron).
- adult female, screening 12-lead ECG, if done, showing prolonged QTc will stop the mother from receiving any study drug but her neonate can still be included in the study.
- adult female, not dependent on opioids for at least 3 weeks prior to delivery.
- adult female, generally not healthy.
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 |
|---|---|---|
| OndansetronAlso: ZofranPregnant women may receive a second dose of IV ondansetron if they have not delivered within 4 hours of receiving the IV study medication. 50% of the 90 mother/baby pairs will receive ondansetron; the baby will always get the same study medication as the mother. | Drug | Ondansetron |
| PlaceboAlso: IV Normal saline; oral simple syrupAll doses of placebo, whether IV or oral, will mimic the same volume as the ondansetron group to maintain the blind. Pregnant women may receive a second dose of IV placebo if they have not delivered within 4 hours of being given the IV study medication. 50% of the 90 mother/baby pairs will receive placebo; the baby will always receive the same study medication as the mother. | Drug | Placebo |
Primary outcome
Number of Participants With Neonatal Abstinence Syndrome
Time frame: 35 days
The incidence of neonatal abstinence syndrome (NAS) measured as the number of neonates who need for morphine treatment for the symptoms of neonatal opioid withdrawal syndrome (NOWS) while the neonates received study medication and for the 30 days after stopping the study medication.
3 secondary outcomes
Length of Hospital Stay
Time frame: At Day 15 and up to 64 days
Total Dose of Narcotic Required to Treat the Symptoms of NAS
Time frame: 15 days
Number of Participants Requiring Adjunctive Medication to Treat NOWS
Time frame: 15 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36030327Peltz G, Jansson LM, Adeniyi-Jones S, Cohane C, Drover D, Shafer S, Wang M, Wu M, Govindaswami B, Jegatheesan P, Argani C, Khan S, Kraft WK. Ondansetron to reduce neonatal opioid withdrawal severity a randomized clinical trial. J Perinatol. 2023 Mar;43(3):271-276. doi: 10.1038/s41372-022-01487-2. Epub 2022 Aug 27.
- Individual participant dataSharing planned: No. We will not share any individual participant data with other researchers.
Related trials for Narcotic Addiction
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Active, not recruiting
Pain Self-Management and Treatment Engagement for Patients Taking Opioids
Chronic Pain, Opioid Use Disorder
Not yet recruiting
QAIAx - SGI/SI Smart Health Cities: Microcity Enclave Program (Quantum SI/AGI Agency a/k/a AI City Hall Project - UPSTO App Nos. 64/074,526, 64/063,557, 64/105,164, 63/903,181, 63/729,428, 64/125,360; USPTO EO 9424 Assignment ID: 2101042 / ARN: REEL/FRAME: 76481/0026 - OUSD-R&E, Department of War)
Asperger's Disorder, Asperger Disorder
RecruitingObservational study
Outcome Inference in the Sensory Preconditioning Task in Opioid-Use Disorder
Opioid-Related Disorders, Drug Addiction
Active, not recruiting
The MOUD Plus Pilot: Counseling and Peer Support to Support Retention for Medically Complex Patients With Opioid Use Disorder Seen In Primary Care
Opioid Dependence, Substance Abuse Disorders
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.
David R Drover, MD principal investigator
Stanford University
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ondansetron in people with Narcotic Addiction and Neonatal Abstinence Syndrome, run by Stanford University at 8 sites 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 6 inclusion and 9 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 7 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 10 May 2022). 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?
Number of Participants With Neonatal Abstinence Syndrome (time frame: 35 days). 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 NCT01965704, 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 7 Jun 2022.