Metabolic Pattern of Cyclosporine A and Acute Renal Failure
Information source: University of Oslo School of Pharmacy
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Heart Transplantation; Acute Renal Failure
Intervention: cyclosporine A (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: University of Oslo School of Pharmacy Official(s) and/or principal investigator(s):
Anders Åsberg, Ph.D., Study Director, Affiliation: University of Oslo School of Pharmacy
Arnt Fiane, MD, Ph.D., Principal Investigator, Affiliation: Rikshospitalet, Department of Thoracic surgery
Summary
Following heart transplantation many patients develop acute renal failure in the early
posttransplant phase and some are in need of renal replacement therapy for shorter or longer
time. The cause of this acute renal failure is most probably multi factorial but many reports
indicate that cyclosporine has a central role in the pathophysiology and it is generally
recommended to lower the cyclosporine load to patients developing acute renal failure in this
population.
Several in vitro studies on renal cells in culture indicate that the primary metabolites of
cyclosporine (AM1, AM9, AM4N) are less toxic to the kidney than cyclosporine itself. However,
the secondary metabolite AM19 as well as the cyclic metabolites AM1c and AM1c9 has been
associated with decreased renal function and nephrotoxicity renal transplant recipients.
The primary objective of this pilot study is to investigate if the concentrations of
secondary- and cyclic metabolites of cyclosporine (AM19, AM1c, AM1c9) is related to
development of acute renal failure in the early posttransplant phase following heart
transplantation.
Secondary objectives are to investigate associations between genotypes of P-glycoprotein and
CYP3A5 and the metabolic pattern of cyclosporine.
Clinical Details
Official title: Metabolic Pattern of Cyclosporine A - Association of Secondary- and Cyclic Metabolites With Acute Renal Failure in Heart Transplant Recipients
Study design: Diagnostic, Non-Randomized, Open Label, Active Control, Parallel Assignment, Pharmacokinetics Study
Primary outcome: The primary analysis of cyclosporine and metabolite concentrations and ratios will be compared between the patients developing acute renal failure and those who do not
Secondary outcome: Regression analysis comparing concentrations/ratios and actual renal function (continuously parameter)Descriptive listing of cyclosporine and metabolites concentrations in CYP3A5*3/*3 patients compared to the other patients. It is anticipated that an exploratory analysis will be performed to compare the two groups. Descriptive listing of CsA and metabolites concentrations in patients with different combinations of MDR-1 genotypes compared to the other patients. It is anticipated that an exploratory analysis will be performed to compare the two groups.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Heart transplant recipients receiving CsA as part of their immunosuppressive therapy.
- 18 years of age or older.
- Signed informed consent.
Exclusion Criteria:
- None
Locations and Contacts
Rikshospitalet, Department of Thoracic surgery, Oslo Oslo, Norway
Additional Information
Starting date: December 2005
Ending date: June 2007
Last updated: September 5, 2007
|
