Clinical trial NCT01801475: How Pregnant Women and Their Babies Metabolize Ondansetron Compared to a Group of Non-pregnant Women
Official title: Prevention of Neonatal Abstinence Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Postoperative Nausea
Keywords: Pharmacokinetics of ondansetron in women
Pharmacokinetics of ondansetron in neonates
Term pregnancy
Cesarean section
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2013-02-28
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: This is called "Aim 1" of the investigators' NIH grant. Ondansetron (Zofran) is a safe and effective drug used in pregnant women to prevent nausea but the investigators do not know what effect pregnancy may have on the metabolism of Zofran in pregnant women or their babies. Therefore the investigators will enroll approximately 40 pregnant women and their babies and draw blood samples from the mother, the baby and the cord, to determine how much Zofran is in each sample of blood (called the pharmacokinetics or PK of Zofran). The pregnant women will receive Zofran, as a standard-of-care drug, for their scheduled Cesarean Section.

The investigators will also enroll about 20 non-pregnant women undergoing surgery who will receive Zofran as standard-of-care during surgery. In both the pregnant \& the non-pregnant women, the investigators will draw blood samples at the same time points based on number of minutes from the time the Zofran is given. The blood data (PK of Zofran) will help the investigators move into Aim 2 of the study, which will be done in pregnant, narcotic-addicted mothers and their babies who are born addicted to narcotics. Aim 2 will be listed separately as it will be an interventional study.

Detailed description: This phase of the study is Aim 1 and it will lead to Aim 2, which specifically will address the Prevention of Neonatal Abstinence Syndrome (NAS).

NAS is a constellation of narcotic drug withdrawal symptoms that develops in 42-94% of the infants born to narcotic dependent mothers. This severe syndrome, of which there are no preventative treatments, can result in prolonged hospitalization, some of which may be in the neonatal intensive care unit (NICU). The investigators have shown that ondansetron can eliminate or alleviate the symptoms of narcotic drug withdrawal in experimental studies in mice and in humans. Based upon these results, it is quite possible that ondansetron administration to pregnant narcotic-using mothers just prior to delivery, followed by a 3-day period of ondansetron administration to the neonate, could reduce the incidence or severity of NAS symptoms.

AIM 1 is a pharmacokinetic (PK) study of intravenous (IV) ondansetron in three different groups of participants: Study Group #1 = non-pregnant women undergoing surgery; Study Group #2 = pregnant women scheduled for cesarean section delivery; Study Group #3 = viable, full term, singleton neonates born to study group #2 mothers. Group #1 will be given IV ondansetron prior to their surgery and up to 5 PK blood samples will be drawn from an indwelling IV line or by IV stick. The PK samples will be 2-5 ml each and will be drawn at baseline (prior to ondansetron) and then at 7, 15, and 40 min and 8 hours after the ondansetron. Group #2 will be given IV ondansetron prior to their cesarean section and up to 6 PK blood samples will be drawn from an indwelling IV line or by IV stick. The PK samples will be 2-5 ml each and will be drawn at baseline, 7, 15, 40 min and prior to delivery and 8 hours after the ondansetron is given. The Group #3 neonates will provide a section of the umbilical cord from which arterial and venous blood samples will be drawn (this section of cord would normally be thrown out and the parents are consenting to allow the Investigators to take these two samples). Each time the baby has a "Standard-of-Care" lab test ordered by heel stick or needle stick, the investigators will obtain a few drops of blood to place on the special research filter paper to determine how much ondansetron is in the baby's blood. If the parents will allow any extra heel sticks, the Investigators will try to obtain 1-2 samples of blood in the first 6 hours of life. If the parents only want their baby's blood taken at the standard-of-care lab draws, then the first scheduled lab draw is at 24 hours of life for the newborn screening which is a mandated by state law. All blood samples taken for this study are being processed by the investigator, not the Stanford Lab. Also, the investigators are doing the PK analysis of the dried blood spots on the filter paper and the analysis of the frozen plasma samples.

Aim 2 of this NIH grant will be entered separately into ClinicalTrials.gov. It will be a multi-center, randomized, double-blind, placebo-controlled trial to determine whether ondansetron treatment will reduce the incidence or severity of NAS in babies born to narcotic-using mothers.

Eligibility criteria: Inclusion Criteria:

For Non-pregnant Females (Group #1)

1. Age 18-45 yrs inclusive
2. Generally healthy
3. Undergoing any scheduled surgical procedure deemed suitable by the Investigator MD
4. Planned to receive the drug Ondansetron for the surgery
5. Able and willing to sign the informed consent

For Pregnant Females (Group #2)

1. Age 18-45 yrs inclusive
2. Term pregnancy (37 weeks through 41 wks + 6 days)
3. Generally healthy (not morbidly obese)
4. Undergoing a planned C-section or by an unplanned, non-urgent C-section
5. Planned to receive the drug Ondansetron for the surgery
6. Single birth
7. Able and willing to sign the informed consent for herself \& the baby

For the Neonatal Participant (Group #3)

1. Male or female
2. Viable birth
3. Gestational age of 37 weeks through 41 weeks + 6 days
4. Mother gave written consent for baby to participate

Exclusion Criteria:

1. Medical condition that would effect the metabolism of ondansetron
2. Known allergy to ondansetron
3. Use of medications in the last 48 hours, by the pregnant or non-pregnant subjects, that might induce or inhibit the metabolism of ondansetron (such as CYP3A4 inhibitors or inducers)

Primary outcomes:
measure: Volume of Distribution Estimated Pharmacokinetic Parameter
timeFrame: 8 hours for women; 48 hours for neonate.
measure: Metabolic Clearance of Ondasetron
timeFrame: 8 hours for women; 48 hours for neonate.
Secondary outcomes:
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital & Stanford Hospital
state: California
Study officials:
affiliation: Stanford University School of Medicine, Department of Anesthesia
name: David R. Drover, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Elkomy MH, Sultan P, Carvalho B, Peltz G, Wu M, Clavijo C, Galinkin JL, Drover DR. Ondansetron pharmacokinetics in pregnant women and neonates: towards a new treatment for neonatal abstinence syndrome. Clin Pharmacol Ther. 2015 Feb;97(2):167-76. doi: 10.1002/cpt.5. Epub 2014 Dec 4.