Metabolic Pattern of Cyclosporine A and Acute Renal Failure

Acute Renal Failure Clinical Trial

Official title:

Metabolic Pattern of Cyclosporine A - Association of Secondary- and Cyclic Metabolites With Acute Renal Failure in Heart Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00264355
• Other study ID #: HeartTx-ARF
• Status: Completed
• Phase: Phase 4
• First received: December 9, 2005
• Last updated: September 5, 2007
• Start date: December 2005
• Est. completion date: June 2007

Study information

• Verified date: September 2007
• Source: University of Oslo School of Pharmacy
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway: Norwegian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Heart transplant recipients receiving CsA as part of their immunosuppressive therapy.

• 18 years of age or older.

• Signed informed consent.

Exclusion Criteria:

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Acute Kidney Injury
• Acute Renal Failure
• Heart Transplantation
• Renal Insufficiency

Intervention

Drug:
• cyclosporine A

Locations

Country	Name	City	State
Norway	Rikshospitalet, Department of Thoracic surgery	Oslo

Sponsors (1)

Lead Sponsor	Collaborator
University of Oslo School of Pharmacy

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Regression analysis comparing concentrations/ratios and actual renal function (continuously parameter)
Secondary	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.
Secondary	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.