Voriconazole Pharmacokinetics in Children With Gastrointestinal Graft Versus Host Disease

Graft Versus Host Disease Clinical Trial

Official title:

Define the Pharmacokinetics of Oral Voriconazole in Children With Extensive Gastrointestinal Graft Versus Host Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00792246
• Other study ID #: Pro00004318
• Status: Completed
• Phase: Phase 1
• Start date: December 2008
• Est. completion date: July 2012

Study information

• Verified date: August 2018
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease
• Stem Cell Transplantation

Intervention

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

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Phillip Brian Smith	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduced bioavailability of oral voriconazole in pediatric patients status post stem cell transplantation with gastrointestinal graft versus host disease		one year
Secondary	Pharmacokinetics(including clearance, maximum concentration, area under the time concentration curve, and half life) of voriconazole in pediatric patients status post hematopoietic stem cell transplantation.		one year