Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

BK Viremia After Renal Transplantation

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2009 by Karolinska University Hospital.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Uppsala University Hospital
Information provided by:
Karolinska University Hospital
ClinicalTrials.gov Identifier:
NCT00684372
First received: May 21, 2008
Last updated: February 5, 2009
Last verified: February 2009

May 21, 2008
February 5, 2009
May 2007
May 2009   (final data collection date for primary outcome measure)
Renal function (serum creatinine) [ Time Frame: 1 year after diagnosis of BK viremia ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00684372 on ClinicalTrials.gov Archive Site
Incidence of BK virus associated nephropathy [ Time Frame: 1 year after diagnosis of BK viremia ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
BK Viremia After Renal Transplantation
BK Viremia After Renal Transplantation: Screening, Early Diagnosis, Early Reduction in Immunosuppression and Treatment With Leflunomide (Arava)

Hypothesis: Early detection, and treatment, of BK virus infection after kidney transplantation will prevent BK virus associated kidney transplant injury.

BK virus associated nephropathy (BKVN) is estimated to cause a progressive kidney transplant injury in 1-10% of renal transplant recipients. Diagnostic and monitoring strategies for BKVN is still being developed. Detectable virus in the blood by polymerase change reaction-test (PCR) is predictive of BKVN. Additionally, PCR provides a objective estimate of the degree of infection.

If early detection and treatment of BK virus infection is effective in preventing subsequent kidney transplant injury has not been studied. However, renal injury and dysfunction develops late in the natural course of BKVN and it seems likely that screening in combination with early treatment would be beneficial for long-term transplant survival.

There is no established treatment for BK virus infection. Nevertheless, in kidney transplanted patients diagnosed with BK virus infection, immunosuppression is reduced to allow the patients own immune system to handle the virus. However, reduction of immunosuppression has not been associated with rejection. This indicate that these patients were over-immunosuppressed, predisposing them to BKVN. Therefore, to compare the degree of immunosuppression in BKVN patients (over-immunosuppressed) to other patients (not over-immunosuppressed) could yield interesting information. One possibility would be to quantify these patients specific cellular immune response to BK virus but also to other viruses (T cell reactivity).

Leflunomide (Arava) is an immunosuppressive drug, approved for the treatment of rheumatoid arthritis, and has been used in more than 300,000 patients worldwide. Furthermore, leflunomide has been used safely in humans after clinical kidney and liver transplantation for more than 300 days. In addition to leflunomide's value in preventing rejection, it has been shown to exert inhibitory effects on different viruses. Recently published pilot studies suggest that leflunomide treatment of patients with BKVN significantly reduces the amount of BK virus in blood and prevents recurrence of kidney transplant injury. At Karolinska University Hospital, leflunomide has been used for treatment of BKVN and, in some of the patients, renal function has stabilized and BK virus load has decreased significantly.

Not Provided
Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Terminal Renal Failure
  • BK Virus Infection
Drug: leflunomide

Screening: If BK viremia (BK PCR >10 000 copies/ml in serum) i. Reduced immunosuppression

  1. MMF / AZA withdrawal
  2. CNI reduction

    1. Tacrolimus 5 ng/ml in serum
    2. Cyclosporin 100 ng/ml in serum
  3. Prednisolone to maintenance level

If effective => continue

  • Stable renal function (P-Krea)
  • >50% reduction in PCR (copies/ml) at 4 weeks after diagnosis
  • Negative PCR at > 3 months after diagnosis

If failure => add leflunomide

  • Deteriorating renal function (P-Krea) and positive PAD = BK nephropathy
  • <50% reduction in PCR at 4 weeks after diagnosis
  • Positive PCR at >3 months after diagnosis

Leflunomide dosing:

ii. Loading dose of 100 mgx1 PO daily for 5 days can be used or the patient can be directly started on iii. Maintenance dose (from day 1 or day 6)

  1. Starting at 20 mgx1 PO daily
  2. Thereafter adjusted between approximately 20-60 mgx1 PO daily according to serum levels of A77 1726 and the clinical situation a. Recommended level of A77 1726 >40 ug/ml
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
100
May 2009
May 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • All adult patients undergoing kidney transplantation at Karolinska University Hospital

Exclusion Criteria:

  • Absence of informed consent
  • Allergy to leflunomide
  • Pregnancy
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Sweden
 
NCT00684372
BK study
Yes
Lars Wennberg, Associate Professor, Karolinska University Hospital
Karolinska University Hospital
Uppsala University Hospital
Principal Investigator: Lars Wennberg, MD, PhD Karolinska University Hospital
Karolinska University Hospital
February 2009

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