Can Ondansetron Prevent Neonatal Abstinence Syndrome (NAS) in Babies Born to Narcotic-dependent Women

Neonatal Abstinence Syndrome Clinical Trial

— AIM2NAS  

Official title:

AIM 2- Prevention of Neonatal Abstinence Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01965704
• Other study ID #: Aim 2_RO1-HD-070795-01A1
• Secondary ID: NAS2
• Status: Completed
• Phase: Phase 2
• Start date: September 9, 2014
• Est. completion date: September 16, 2020

Study information

• Verified date: June 2022
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 196
• Est. completion date: September 16, 2020
• Est. primary completion date: September 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 45 Years

Eligibility

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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.

• 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.

Related Conditions & MeSH terms

• Behavior, Addictive
• Narcotic Addiction
• Neonatal Abstinence Syndrome
• Syndrome

Intervention

Drug:
• Ondansetron
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.
• Placebo
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.

Locations

Country	Name	City	State
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland
United States	University of Louisville	Louisville	Kentucky
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	The University of Utah	Salt Lake City	Utah
United States	UCSF, San Francisco General Hospital	San Francisco	California
United States	Santa Clara Valley Medical Center	San Jose	California
United States	Stanford University Medical Center	Stanford	California

Sponsors (3)

Lead Sponsor	Collaborator
Stanford University	Santa Clara Valley Medical Center, Thomas Jefferson University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	35 days
Secondary	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.	At Day 15 and up to 64 days
Secondary	Total Dose of Narcotic Required to Treat the Symptoms of NAS	Median dose of morphine required by neonates within 15 days of delivery.	15 days
Secondary	Number of Participants Requiring Adjunctive Medication to Treat NOWS	Number of neonates requiring treatment with phenobarbital or clonidine.	15 days