How Pregnant Women and Their Babies Metabolize Ondansetron Compared to a Group of Non-pregnant Women (Zofran_PK)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
David R. Drover, Stanford University
ClinicalTrials.gov Identifier:
NCT01801475
First received: January 28, 2013
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Postoperative Nausea
Drug: Ondansetron
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Prevention of Neonatal Abstinence Syndrome

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Amount of Ondansetron, in ng/ml, in the blood or plasma [ Time Frame: 8 hours for women; 48 hours for neonate. ] [ Designated as safety issue: No ]

    From the women the blood samples are taken up to 6 times from an intravenous line, or from a needle stick if the woman agrees, in the first 8 hours after receiving ondansetron.

    The neonates blood samples are taken any time a standard-of-care heel stick is done (only a few drops of blood are needed) in first 48 hours after birth. If the parents agree, heel sticks may be done for research purposes only, within the first 48 hours of life.



Enrollment: 100
Study Start Date: January 2013
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Pregnant women
Full term pregnant women scheduled for Cesarean section and will be given Ondansetron as standard-of-care prior to surgery.
Drug: Ondansetron
Pregnant & non-pregnant women will receive either 4mg or 8mg of Ondansetron (IV) once prior to surgical procedure (open-label). Women are in the study for 8 hours. Babies of pregnant women are not given Ondansetron but are in the study for 24-48 hours.
Other Name: Zofran
Active Comparator: Non-pregnant women
Non-pregnant women scheduled for surgery at Stanford who will be given Ondansetron prior to their surgery as standard-of-care.
Drug: Ondansetron
Pregnant & non-pregnant women will receive either 4mg or 8mg of Ondansetron (IV) once prior to surgical procedure (open-label). Women are in the study for 8 hours. Babies of pregnant women are not given Ondansetron but are in the study for 24-48 hours.
Other Name: Zofran
No Intervention: Neonates
Babies of the pregnant women enrolled in the study; no ondansetron is given to babies in this "Aim 1" of the 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

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01801475

Locations
United States, California
Lucile Packard Children's Hospital & Stanford Hospital
Palo Alto, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: David R. Drover, MD Stanford University School of Medicine, Department of Anesthesia
  More Information

No publications provided

Responsible Party: David R. Drover, Associate Professor of Anesthesia, Stanford School of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT01801475     History of Changes
Other Study ID Numbers: 1R01HD070795-01A1, NAS Aim 1
Study First Received: January 28, 2013
Last Updated: May 14, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Stanford University:
Pharmacokinetics of ondansetron in women
Pharmacokinetics of ondansetron in neonates
Term pregnancy
Cesarean section

Additional relevant MeSH terms:
Neonatal Abstinence Syndrome
Infant, Newborn, Diseases
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Ondansetron
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Antipruritics
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

ClinicalTrials.gov processed this record on September 18, 2014