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

NCT01965704 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: Aim 2_RO1-HD-070795-01A1NAS2
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 8

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.

Conditions

Narcotic Addiction; Neonatal Abstinence Syndrome

Keywords

Narcotic addiction during pregnancy; Neonatal abstinence syndrome; NAS

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Length of Hospital Stay

  At Day 15 and up to 64 days

• Total Dose of Narcotic Required to Treat the Symptoms of NAS

  15 days

• Number of Participants Requiring Adjunctive Medication to Treat NOWS

  15 days

Study Arms (2)

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).

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).

Drug: Placebo

Interventions

Ondansetron DRUG

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.

Also known as: Zofran

Ondansetron

Placebo DRUG

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.

Also known as: IV Normal saline; oral simple syrup

Placebo

Eligibility Criteria

• Age: Up to 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stanford University: lead
• Santa Clara Valley Medical Center: collaborator
• Thomas Jefferson University: collaborator

Study Sites (8)

UCSF, San Francisco General Hospital

San Francisco, California, 94110, United States

Location

Santa Clara Valley Medical Center

San Jose, California, 95128, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

University of Louisville

Louisville, Kentucky, 40292, United States

Location

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Tennessee Health Science Center

Memphis, Tennessee, 38163, United States

Location

The University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• 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.

  PMID: 36030327 DERIVED

MeSH Terms

Conditions

Narcotic-Related Disorders; Neonatal Abstinence Syndrome

Interventions

Ondansetron; Saline Solution

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: David Drover
• Organization: Stanford University

ddrover@stanford.edu

650-725-0364

Study Officials

• David R Drover, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesiology, Perioperative and Pain Medicine

Study Record Dates

• First Submitted: October 15, 2013
• First Posted: October 18, 2013
• Study Start: September 9, 2014
• Primary Completion: September 3, 2020
• Study Completion: September 16, 2020
• Last Updated: June 7, 2022
• Results First Posted: May 10, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)