Voriconazole Pharmacokinetics in Children With Gastrointestinal Graft Versus Host Disease

NCT ID: NCT00792246

Last Updated: 2018-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2012-07-31

Brief Summary

Determine how much voriconazole is absorbed when the product is given by mouth to children with extensive graft versus host disease after a stem cell transplantation and determine the correct dosing of voriconazole in this population.

Hypothesis: Children with gastrointestinal graft versus host disease will have decreased absorption of oral voriconazole and require higher doses of voriconazole in order to prevent or treat fungal infections.

Detailed Description

Disseminated fungal infections are a leading cause of mortality in children who receive hematopoietic stem cell transplantation (SCT). Therefore, children routinely receive prophylactic and empirical antifungal therapy after SCT. The most commonly used antifungal agent in this population is voriconazole. Voriconazole can be given via intravenous or oral routes and children who are post SCT are routinely switched from the intravenous to oral formulation at the time of hospital discharge. However, the absorption and systemic exposure of oral voriconazole has not been well-described in children. Furthermore, many children who undergo transplantation develop gastrointestinal graft versus host disease and this likely impacts oral absorption. The magnitude of effect resulting from graft versus host disease on absorption of voriconazole and subsequent blood concentrations in children is unknown. Thus children with graft versus host disease are at a particularly high risk of inadequate absorption with subsequent sub-therapeutic levels of voriconazole. They may need higher or more frequent dosing to achieve therapeutic levels. The purpose of my research project is to define the pharmacokinetics of oral voriconazole and establish dosing guidelines in children following SCT.

Conditions

Graft Versus Host Disease; Stem Cell Transplantation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

graft versus host disease

Patients receiving oral voriconazole will be switched to intravenous voriconazole. Pharmacokinetics will be determined after each formulation.

Group Type: EXPERIMENTAL

voriconazole

Intervention Type: DRUG

Voriconazole formulation will be changed from oral to intravenous at the same dose the subject is currently receiving per standard of care.

No graft versus host disease

Patients receiving oral voriconazole will be switched to intravenous voriconazole. Pharmacokinetics will be determined after each formulation.

Group Type: EXPERIMENTAL

voriconazole

Intervention Type: DRUG

Voriconazole formulation will be changed from oral to intravenous at the same dose the subject is currently receiving per standard of care.

Interventions

voriconazole

Voriconazole formulation will be changed from oral to intravenous at the same dose the subject is currently receiving per standard of care.

Intervention Type: DRUG

voriconazole

Voriconazole formulation will be changed from oral to intravenous at the same dose the subject is currently receiving per standard of care.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age ≤ 18 years, sufficient venous access to permit administration of voriconazole, ability to take oral medications, written informed consent provided by the parent or legally authorized representative, and Grade II or higher (extensive) gastrointestinal graft versus host disease for those patients in the graft versus host disease patient subset.

Exclusion Criteria

• History of anaphylaxis attributed to voriconazole or other triazole compounds, any concomitant condition, which in the opinion of the investigator would preclude a patient's participation in the study, or previous participation in this study.

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Phillip Brian Smith

OTHER

Sponsor Role: lead

Responsible Party

Phillip Brian Smith

Associate Professor of Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

P Brian Smith, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Unviersity Medical Center

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Other Identifiers

Pro00004318

Identifier Type: -

Identifier Source: org_study_id