Postoperative NauseaPhase 1/2Zofran_PKNCT01801475
How Pregnant Women and Their Babies Metabolize Ondansetron Compared to a Group of Non-pregnant Women
A Phase 1/2 study testing Ondansetron in people with Postoperative Nausea, run by Stanford University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Postoperative Nausea
- What is being tested?
- Ondansetron
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2013to May 2013
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- For Non-pregnant Females (Group #1)
- Age 18-45 yrs inclusive
- Generally healthy
- Undergoing any scheduled surgical procedure deemed suitable by the Investigator MD
- Planned to receive the drug Ondansetron for the surgery
- Able and willing to sign the informed consent
Show all 19Show fewer
- For Pregnant Females (Group #2)
- Age 18-45 yrs inclusive
- Term pregnancy (37 weeks through 41 wks + 6 days)
- Generally healthy (not morbidly obese)
- Undergoing a planned C-section or by an unplanned, non-urgent C-section
- Planned to receive the drug Ondansetron for the surgery
- Single birth
- Able and willing to sign the informed consent for herself \& the baby
- For the Neonatal Participant (Group #3)
- Male or female
- Viable birth
- Gestational age of 37 weeks through 41 weeks + 6 days
- Mother gave written consent for baby to participate
Who cannot join
- Medical condition that would effect the metabolism of ondansetron
- Known allergy to ondansetron
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Lucile Packard Children's Hospital & Stanford Hospital
Palo Alto, California, 94305
About this study
Official title: Prevention of Neonatal Abstinence Syndrome
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.
Read the 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.
- Conditions
- Postoperative Nausea
- Being tested
- Ondansetron
- Keywords
- Pharmacokinetics of ondansetron in women, Pharmacokinetics of ondansetron in neonates, Term pregnancy, Cesarean section
- Medical subject headings
- Postoperative Nausea and Vomiting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OndansetronDrug
Also called Zofran
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.
| Study group | Role | What they receive |
|---|---|---|
| Pregnant women | Active comparator | Full term pregnant women scheduled for Cesarean section and will be given Ondansetron as standard-of-care prior to surgery. Receives: Drug: Ondansetron |
| Non-pregnant women | Active comparator | Non-pregnant women scheduled for surgery at Stanford who will be given Ondansetron prior to their surgery as standard-of-care. Receives: Drug: Ondansetron |
| Neonates | No intervention | Babies of the pregnant women enrolled in the study; no ondansetron is given to babies in this "Aim 1" of the study. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Volume of Distribution Estimated Pharmacokinetic Parameter
This is an estimated pharmacokinetic parameter as calculated by NONMEM.
Measured: 8 hours for women; 48 hours for neonate.
Metabolic Clearance of Ondasetron
This is a mathematical estimation of the clearance for ondasetron as calculated by NONMEM.
Measured: 8 hours for women; 48 hours for neonate.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2013 (estimated)
- Study startJan 2013
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Postoperative NauseaStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David R. Drover, Stanford University
- Investigators
- David R. Drover, MD, Principal investigator, Stanford University School of Medicine, Department of Anesthesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01801475
- Sponsor's protocol ID
- 1R01HD070795-01A1
- Other IDs
- NAS Aim 1
- Acronym
- Zofran_PK
- Status last verified
- May 2015
- First submitted
- 28 Jan 2013
- Last updated
- 1 Jun 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 25670522
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Neonatal Abstinence Syndrome
- ClinicalTrials.gov ID
- NCT01801475
- Acronym / sponsor ID
- Zofran_PK / 1R01HD070795-01A1
- Conditions
- Postoperative Nausea
- Keywords
- Pharmacokinetics of ondansetron in women, Pharmacokinetics of ondansetron in neonates, Term pregnancy, Cesarean section
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 28 Feb 2013 (estimated)
- Results
- Posted 1 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Pregnant women | Active comparator | Drug: OndansetronFull term pregnant women scheduled for Cesarean section and will be given Ondansetron as standard-of-care prior to surgery. |
| Non-pregnant women | Active comparator | Drug: OndansetronNon-pregnant women scheduled for surgery at Stanford who will be given Ondansetron prior to their surgery as standard-of-care. |
| Neonates | No intervention | –Babies of the pregnant women enrolled in the study; no ondansetron is given to babies in this "Aim 1" of the study. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- For Non-pregnant Females (Group #1)
- Age 18-45 yrs inclusive
- Generally healthy
- Undergoing any scheduled surgical procedure deemed suitable by the Investigator MD
- Planned to receive the drug Ondansetron for the surgery
Key exclusion criteria (3 listed)
- Medical condition that would effect the metabolism of ondansetron
- Known allergy to ondansetron
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OndansetronAlso: ZofranPregnant \& 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. | Drug | Non-pregnant women, Pregnant women |
Primary outcome
Volume of Distribution Estimated Pharmacokinetic Parameter
Time frame: 8 hours for women; 48 hours for neonate.
This is an estimated pharmacokinetic parameter as calculated by NONMEM.
Metabolic Clearance of Ondasetron
Time frame: 8 hours for women; 48 hours for neonate.
This is a mathematical estimation of the clearance for ondasetron as calculated by NONMEM.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25670522Elkomy 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David R. Drover, MD principal investigator
Stanford University School of Medicine, Department of Anesthesia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ondansetron in people with Postoperative Nausea, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Volume of Distribution Estimated Pharmacokinetic Parameter (time frame: 8 hours for women; 48 hours for neonate.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01801475, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2015.