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

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ClinicalTrials.gov Identifier: NCT01965704
Recruitment Status : Recruiting
First Posted : October 18, 2013
Last Update Posted : January 1, 2018
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Narcotic Addiction Neonatal Abstinence Syndrome Drug: Ondansetron Drug: Placebo Phase 2

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: AIM 2- Prevention of Neonatal Abstinence Syndrome
Study Start Date : December 2013
Estimated Primary Completion Date : April 2018
Estimated Study Completion Date : June 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Ondansetron
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).
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.
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).

Drug: 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.
Other Name: IV Normal saline; oral simple syrup

Outcome Measures

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01965704

Contact: Carol A Cohane, RN 650-736-8231 cohane@stanford.edu

United States, California
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305
Contact: Carol A Cohane, RN       cohane@stanford.edu   
Principal Investigator: David R Drover, MD         
Sponsors and Collaborators
Stanford University
Santa Clara Valley Medical Center
University of California, San Francisco
University of Utah
Johns Hopkins University
University of Tennessee Health Science Center
University of Louisville
Thomas Jefferson University
Principal Investigator: David R Drover, MD Stanford University
More Information

Responsible Party: David R. Drover, Associate Professor of Anesthesia, Stanford School of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT01965704     History of Changes
Other Study ID Numbers: Aim 2_RO1-HD-070795-01A1
NAS2 ( Other Identifier: Stanford )
First Posted: October 18, 2013    Key Record Dates
Last Update Posted: January 1, 2018
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: We will not share any individual participant data with other researchers.

Keywords provided by David R. Drover, Stanford University:
Narcotic addiction during pregnancy
Neonatal abstinence syndrome

Additional relevant MeSH terms:
Opioid-Related Disorders
Behavior, Addictive
Neonatal Abstinence Syndrome
Pathologic Processes
Compulsive Behavior
Impulsive Behavior
Infant, Newborn, Diseases
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Dermatologic Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Anti-Anxiety Agents