Can Ondansetron Prevent Neonatal Abstinence Syndrome (NAS) in Babies Born to Narcotic-dependent Women (AIM2NAS)
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.
|Narcotic Addiction Neonatal Abstinence Syndrome||Drug: Ondansetron Drug: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Prevention
|Official Title:||AIM 2- Prevention of Neonatal Abstinence Syndrome|
- Incidence of neonatal abstinence syndrome [ Time Frame: 35 days ]The incidence of neonatal abstinence syndrome (NAS) will be measured by the need for pharmacologic treatment for the symptoms of NAS while the neonates are receiving study medication and for the 30 days after stopping the study medication.
- Severity of neonatal abstinence syndrome [ Time Frame: 35 days ]Severity of NAS will be measured by: the length of hospital stay (birth to discharge); the total dose of narcotic required to treat the symptoms of NAS; and the need to include barbiturates in the treatment of the symptoms of NAS.
|Study Start Date:||December 2013|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
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).
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.
Other Name: Zofran
Placebo Comparator: Placebo
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).
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.
Other Name: IV Normal saline; oral simple syrup
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01965704
|Contact: Carol A Cohane, RNemail@example.com|
|United States, California|
|Stanford University Medical Center||Recruiting|
|Stanford, California, United States, 94305|
|Contact: Carol A Cohane, RN firstname.lastname@example.org|
|Principal Investigator: David R Drover, MD|
|Principal Investigator:||David R Drover, MD||Stanford University|