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

NCT ID: NCT01965704

Last Updated: 2022-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 196 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-09
• Study Completion Date: 2020-09-16

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.

Conditions

Narcotic Addiction; Neonatal Abstinence Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Ondansetron

Intervention Type: 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.

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Zofran; IV Normal saline; oral simple syrup

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.

• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Santa Clara Valley Medical Center

OTHER

Sponsor Role: collaborator

Thomas Jefferson University

OTHER

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

David R. Drover

Professor of Anesthesiology, Perioperative and Pain Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David R Drover, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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, United States

University of Louisville

Louisville, Kentucky, United States

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

University of Tennessee Health Science Center

Memphis, Tennessee, United States

The University of Utah

Salt Lake City, Utah, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36030327 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: Parental Permission

View Document

Document Type: Informed Consent Form: Maternal ICF

View Document

Other Identifiers

NAS2

Identifier Type: OTHER

Identifier Source: secondary_id

Aim 2_RO1-HD-070795-01A1

Identifier Type: -

Identifier Source: org_study_id