Gastrointestinal Implications of Voriconazole Exposure

NCT02904434 | Withdrawn

• 1 other identifier: 16-012970
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Infection

Keywords

voriconazole; absorption; pharmacokinetic; grapefruit juice; bioavailability; intestinal first-pass metabolism; pharmacokinetics; intestinal

Outcome Measures

Primary Outcomes (1)

• VoriconazoleArea Under the Curve (AUC)

  Pharmacokinetic samples will be collected

  Two days

Secondary Outcomes (2)

• Voriconazole Apparent Bioavailability

  Two days

• Voriconazole Apparent Clearance

  Two days

Study Arms (1)

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

Interventions

Grapefruit Juice OTHER

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.

Voriconazole

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood will be drawn during 12 hours following voriconazole administration. Samples will be analyzed for voriconazole concentrations.

MeSH Terms

Conditions

Infections

Study Officials

• Athena Zuppa, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2016
• First Posted: September 19, 2016
• Study Start: September 1, 2016
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: April 9, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)