search
Back to results

Can Ondansetron Prevent Neonatal Abstinence Syndrome (NAS) in Babies Born to Narcotic-dependent Women (AIM2NAS)

Primary Purpose

Narcotic Addiction, Neonatal Abstinence Syndrome

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ondansetron
Placebo
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Narcotic Addiction focused on measuring Narcotic addiction during pregnancy, Neonatal abstinence syndrome, NAS

Eligibility Criteria

undefined - 45 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UCSF, San Francisco General Hospital
  • Santa Clara Valley Medical Center
  • Stanford University Medical Center
  • University of Louisville
  • Johns Hopkins Bayview Medical Center
  • Thomas Jefferson University Hospital
  • University of Tennessee Health Science Center
  • The University of Utah

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ondansetron

Placebo

Arm Description

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: 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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Total Dose of Narcotic Required to Treat the Symptoms of NAS
Median dose of morphine required by neonates within 15 days of delivery.
Number of Participants Requiring Adjunctive Medication to Treat NOWS
Number of neonates requiring treatment with phenobarbital or clonidine.

Full Information

First Posted
October 15, 2013
Last Updated
June 6, 2022
Sponsor
Stanford University
Collaborators
Santa Clara Valley Medical Center, Thomas Jefferson University
search

1. Study Identification

Unique Protocol Identification Number
NCT01965704
Brief Title
Can Ondansetron Prevent Neonatal Abstinence Syndrome (NAS) in Babies Born to Narcotic-dependent Women
Acronym
AIM2NAS
Official Title
AIM 2- Prevention of Neonatal Abstinence Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
September 9, 2014 (Actual)
Primary Completion Date
September 3, 2020 (Actual)
Study Completion Date
September 16, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
Collaborators
Santa Clara Valley Medical Center, Thomas Jefferson University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Narcotic Addiction, Neonatal Abstinence Syndrome
Keywords
Narcotic addiction during pregnancy, Neonatal abstinence syndrome, NAS

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
196 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ondansetron
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Ondansetron
Other Intervention Name(s)
Zofran
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
IV Normal saline; oral simple syrup
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants With Neonatal Abstinence Syndrome
Description
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.
Time Frame
35 days
Secondary Outcome Measure Information:
Title
Length of Hospital Stay
Description
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.
Time Frame
At Day 15 and up to 64 days
Title
Total Dose of Narcotic Required to Treat the Symptoms of NAS
Description
Median dose of morphine required by neonates within 15 days of delivery.
Time Frame
15 days
Title
Number of Participants Requiring Adjunctive Medication to Treat NOWS
Description
Number of neonates requiring treatment with phenobarbital or clonidine.
Time Frame
15 days

10. Eligibility

Sex
All
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David R Drover, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCSF, San Francisco General Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
Santa Clara Valley Medical Center
City
San Jose
State/Province
California
ZIP/Postal Code
95128
Country
United States
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40292
Country
United States
Facility Name
Johns Hopkins Bayview Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Tennessee Health Science Center
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38163
Country
United States
Facility Name
The University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
We will not share any individual participant data with other researchers.
Citations:
PubMed Identifier
36030327
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs