GIVE: Gastrointestinal Implications of Voriconazole Exposure

Sponsor
Children's Hospital of Philadelphia (Other)
Overall Status
Withdrawn
CT.gov ID
NCT02904434
Collaborator
(none)
0
1
45
0

Study Details

Study Description

Brief 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. This study aims to understand the physiological differences between children and adults that leads to therapeutic failure of voriconazole in children.

Condition or Disease Intervention/Treatment Phase
  • Other: Grapefruit Juice

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

Study Type:
Observational
Actual Enrollment :
0 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Gastrointestinal Implications of Voriconazole Exposure: Determining Age-dependent Differences in Intestinal Metabolism Affecting Oral Bioavailability of Voriconazole in Children
Study Start Date :
Sep 1, 2016
Anticipated Primary Completion Date :
Jun 1, 2020
Anticipated Study Completion Date :
Jun 1, 2020

Arms and Interventions

Arm Intervention/Treatment
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.

Other: Grapefruit Juice
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.

Outcome Measures

Primary Outcome Measures

  1. VoriconazoleArea Under the Curve (AUC) [Two days]

    Pharmacokinetic samples will be collected

Secondary Outcome Measures

  1. Voriconazole Apparent Bioavailability [Two days]

    Pharmacokinetic samples will be collected

  2. Voriconazole Apparent Clearance [Two days]

    Pharmacokinetic samples will be collected

Eligibility Criteria

Criteria

Ages Eligible for Study:
2 Years to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Children aged 2-17 years old

  2. 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)

  3. Informed Consent/Assent when appropriate

Exclusion Criteria:
  1. Allergy or inability to receive the slushy solution, which will be prepared using commercially available frozen grapefruit juice concentrate, cherry syrup, and Sprite.

  2. Receiving tacrolimus and/or cyclosporine, which are affected by the furanocoumarins, during study period

  3. 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)

  4. Receiving renal replacement therapy (example peritoneal dialysis, hemodialysis, continuous veno-venous hemofiltration, continuous veno-venous hemodialysis)

  5. Receiving therapy with extracorporeal membrane oxygenation (ECMO)

  6. Patients with documented pancytopenia, diarrhea, mucositis, or active infection

Contacts and Locations

Locations

Site City State Country Postal Code
1 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104

Sponsors and Collaborators

  • Children's Hospital of Philadelphia

Investigators

  • Principal Investigator: Athena Zuppa, MD, Children's Hospital of Philadelphia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT02904434
Other Study ID Numbers:
  • 16-012970
First Posted:
Sep 19, 2016
Last Update Posted:
Apr 9, 2020
Last Verified:
Apr 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Children's Hospital of Philadelphia

Study Results

No Results Posted as of Apr 9, 2020