InfectionGIVENCT02904434
Gastrointestinal Implications of Voriconazole Exposure
An observational study of Infection, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial summary
Voriconazole has better response rates, improved survival and less adverse side effects compared to other drugs for the treatment of invasive fungal infections making it a desirable therapeutic option for children. However, dosing is unpredictable in children and this leads to therapeutic failure. Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Infection
- What is being tested?
- Grapefruit Juice
- Type of treatment
- Pill or oral medicine
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2016to Jun 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
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 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Study population: Children (2-17 years old) who are being treated at The Children's Hospital of Philadelphia and receiving oral voriconazole as standard of care will be eligible to enroll in this trial.
Who may be able to join
- Children aged 2-17 years old
- Receiving oral voriconazole as standard of care and at steady-state concentrations (defined as 72 hours from first-dose or 72 hours with no dose change)
- Informed Consent/Assent when appropriate
Who cannot join
- Allergy or inability to receive the slushy solution, which will be prepared using commercially available frozen grapefruit juice concentrate, cherry syrup, and Sprite.
- Receiving tacrolimus and/or cyclosporine, which are affected by the furanocoumarins, during study period
- Suspected or known hepatic dysfunction (defined as liver function tests measured at 3x upper limit of normal within the past 1 month, when measured as standard of care)
- Receiving renal replacement therapy (example peritoneal dialysis, hemodialysis, continuous veno-venous hemofiltration, continuous veno-venous hemodialysis)
- Receiving therapy with extracorporeal membrane oxygenation (ECMO)
- Patients with documented pancytopenia, diarrhea, mucositis, or active infection
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Gastrointestinal Implications of Voriconazole Exposure: Determining Age-dependent Differences in Intestinal Metabolism Affecting Oral Bioavailability of Voriconazole in Children
Voriconazole has better response rates, improved survival and less adverse side effects compared to other drugs for the treatment of invasive fungal infections making it a desirable therapeutic option for children. However, dosing is unpredictable in children and this leads to therapeutic failure. This study aims to understand the physiological differences between children and adults that leads to therapeutic failure of voriconazole in children.
Read the detailed description
Voriconazole clearance in children (2-12 years old) is 3-fold higher and bioavailability is one half of adult values. An important gap in knowledge exists that explain the mechanisms that result in higher clearance and lower bioavailability of voriconazole and places children at a substantial risk for sub-therapeutic concentrations and treatment failures. Preliminary data suggests that intestinal first-pass metabolism is responsible for the lower bioavailability in children, but not in adults. By inhibiting intestinal metabolism with grapefruit juice, the extent of the effect of intestinal first-pass metabolism on voriconazole pharmacokinetics can be determined. Inpatient children at the Children's Hospital of Philadelphia who are receiving oral voriconazole as standard of care will be enrolled in an open label, cross-over clinical trial to monitor plasma voriconazole levels after voriconazole administration with and without grapefruit juice to inhibit intestinal metabolism of voriconazole. The proposed research will elucidate the role of intestinal metabolism in the reduced oral bioavailability of voriconazole in children, which can be incorporated into a model simulation to guide accurate dosing.
- Conditions
- Infection
- Being tested
- Grapefruit Juice
- Keywords
- voriconazole, absorption, pharmacokinetic, grapefruit juice, bioavailability, intestinal first-pass metabolism, pharmacokinetics, intestinal
- Medical subject headings
- Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Grapefruit JuiceOther
On day 1 of the study, subjects will receive their standard voriconazole dose with no grapefruit juice. On day 2 of the study, subjects will receive approximately 240mL of reconstituted grapefruit juice by mouth or via nasogastric tube 30 minutes prior to receiving a scheduled dose of voriconazole. Blood samples will be collected during the 12 hours following voriconazole dosing on both days of the study.
| Study group | Role | What they receive |
|---|---|---|
| Voriconazole | Children (2-17 years old) will receive oral voriconazole as prescribed by their physicians as standard of care for the duration of the study. Receives: Other: Grapefruit Juice |
What is being measured
The primary outcome is the main question the study is designed to answer.
VoriconazoleArea Under the Curve (AUC)
Pharmacokinetic samples will be collected
Measured: Two days
Secondary outcomes (2)
Voriconazole Apparent Bioavailability
Pharmacokinetic samples will be collected
Measured: Two days
Voriconazole Apparent Clearance
Pharmacokinetic samples will be collected
Measured: Two days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2016 (estimated)
- Study startSep 2016
- Primary completionJun 2020 (estimated)
- Study completionJun 2020 (estimated)
Why it stopped: IRB terminated the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfectionStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Athena Zuppa, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02904434
- Sponsor's protocol ID
- 16-012970
- Acronym
- GIVE
- Status last verified
- Apr 2020
- First submitted
- 7 Sep 2016
- Last updated
- 9 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gastrointestinal Implications of Voriconazole Exposure: Determining Age-dependent Differences in Intestinal Metabolism Affecting Oral Bioavailability of Voriconazole in Children
- ClinicalTrials.gov ID
- NCT02904434
- Acronym / sponsor ID
- GIVE / 16-012970
- Conditions
- Infection
- Keywords
- voriconazole, absorption, pharmacokinetic, grapefruit juice, bioavailability, intestinal first-pass metabolism, pharmacokinetics, intestinal
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: IRB terminated the study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Study start
- Sep 2016
- Primary completion
- Jun 2020 (estimated)
- Study completion
- Jun 2020 (estimated)
- First posted
- 19 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Voriconazole has better response rates, improved survival and less adverse side effects compared to other drugs for the treatment of invasive fungal infections making it a desirable therapeutic option for children. However, dosing is unpredictable in children and this leads to therapeutic failure. This study aims to understand the physiological differences between children and adults that leads to therapeutic failure of voriconazole in children.
Detailed description
Voriconazole clearance in children (2-12 years old) is 3-fold higher and bioavailability is one half of adult values. An important gap in knowledge exists that explain the mechanisms that result in higher clearance and lower bioavailability of voriconazole and places children at a substantial risk for sub-therapeutic concentrations and treatment failures. Preliminary data suggests that intestinal first-pass metabolism is responsible for the lower bioavailability in children, but not in adults. By inhibiting intestinal metabolism with grapefruit juice, the extent of the effect of intestinal first-pass metabolism on voriconazole pharmacokinetics can be determined. Inpatient children at the Children's Hospital of Philadelphia who are receiving oral voriconazole as standard of care will be enrolled in an open label, cross-over clinical trial to monitor plasma voriconazole levels after voriconazole administration with and without grapefruit juice to inhibit intestinal metabolism of voriconazole. The proposed research will elucidate the role of intestinal metabolism in the reduced oral bioavailability of voriconazole in children, which can be incorporated into a model simulation to guide accurate dosing.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Voriconazole | – | Other: Grapefruit JuiceChildren (2-17 years old) will receive oral voriconazole as prescribed by their physicians as standard of care for the duration of the study. |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Children (2-17 years old) who are being treated at The Children's Hospital of Philadelphia and receiving oral voriconazole as standard of care will be eligible to enroll in this trial.
Key inclusion criteria (3 listed)
- Children aged 2-17 years old
- Receiving oral voriconazole as standard of care and at steady-state concentrations (defined as 72 hours from first-dose or 72 hours with no dose change)
- Informed Consent/Assent when appropriate
Key exclusion criteria (6 listed)
- Allergy or inability to receive the slushy solution, which will be prepared using commercially available frozen grapefruit juice concentrate, cherry syrup, and Sprite.
- Receiving tacrolimus and/or cyclosporine, which are affected by the furanocoumarins, during study period
- Suspected or known hepatic dysfunction (defined as liver function tests measured at 3x upper limit of normal within the past 1 month, when measured as standard of care)
- Receiving renal replacement therapy (example peritoneal dialysis, hemodialysis, continuous veno-venous hemofiltration, continuous veno-venous hemodialysis)
- Receiving therapy with extracorporeal membrane oxygenation (ECMO)
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 |
|---|---|---|
| Grapefruit JuiceOn day 1 of the study, subjects will receive their standard voriconazole dose with no grapefruit juice. On day 2 of the study, subjects will receive approximately 240mL of reconstituted grapefruit juice by mouth or via nasogastric tube 30 minutes prior to receiving a scheduled dose of voriconazole. Blood samples will be collected during the 12 hours following voriconazole dosing on both days of the study. | Other | Voriconazole |
Primary outcome
VoriconazoleArea Under the Curve (AUC)
Time frame: Two days
Pharmacokinetic samples will be collected
2 secondary outcomes
Voriconazole Apparent Bioavailability
Time frame: Two days
Voriconazole Apparent Clearance
Time frame: Two days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2020.
- Individual participant dataSharing planned: No
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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.
Athena Zuppa, MD principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Infection, run by Children's Hospital of Philadelphia 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 3 inclusion and 6 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: withdrawn, as of the sponsor's last update on 9 Apr 2020. 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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
VoriconazoleArea Under the Curve (AUC) (time frame: Two days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Apr 2020.