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Voriconazole Pharmacokinetics in Children With Gastrointestinal Graft Versus Host Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00792246
Recruitment Status : Completed
First Posted : November 17, 2008
Last Update Posted : September 4, 2018
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Phillip Brian Smith, Duke University

Tracking Information
First Submitted Date  ICMJE November 13, 2008
First Posted Date  ICMJE November 17, 2008
Last Update Posted Date September 4, 2018
Study Start Date  ICMJE December 2008
Actual Primary Completion Date July 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2008)
Reduced bioavailability of oral voriconazole in pediatric patients status post stem cell transplantation with gastrointestinal graft versus host disease [ Time Frame: one year ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2008)
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. [ Time Frame: one year ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Voriconazole Pharmacokinetics in Children With Gastrointestinal Graft Versus Host Disease
Official Title  ICMJE Define the Pharmacokinetics of Oral Voriconazole in Children With Extensive Gastrointestinal Graft Versus Host Disease
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Graft Versus Host Disease
  • Stem Cell Transplantation
Intervention  ICMJE Drug: voriconazole
Voriconazole formulation will be changed from oral to intravenous at the same dose the subject is currently receiving per standard of care.
Study Arms  ICMJE
  • Experimental: graft versus host disease
    Patients receiving oral voriconazole will be switched to intravenous voriconazole. Pharmacokinetics will be determined after each formulation.
    Intervention: Drug: voriconazole
  • Experimental: No graft versus host disease
    Patients receiving oral voriconazole will be switched to intravenous voriconazole. Pharmacokinetics will be determined after each formulation.
    Intervention: Drug: voriconazole
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 14, 2012)
5
Original Estimated Enrollment  ICMJE
 (submitted: November 13, 2008)
36
Actual Study Completion Date  ICMJE July 2012
Actual Primary Completion Date July 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00792246
Other Study ID Numbers  ICMJE Pro00004318
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Phillip Brian Smith, Duke University
Study Sponsor  ICMJE Phillip Brian Smith
Collaborators  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
Principal Investigator: P Brian Smith, MD Duke Unviersity Medical Center
PRS Account Duke University
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP