Terminal Renal FailureNCT00684372
BK Viremia After Renal Transplantation
A study testing leflunomide in people with Terminal Renal Failure and BK Virus Infection, run by Karolinska University Hospital at 1 site in Sweden.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Terminal Renal Failure, BK Virus Infection
- What is being tested?
- leflunomide
- How many people
- 100 participants
- Where
- 1 siteSweden
- Study dates
- May 2007to May 2009
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All adult patients undergoing kidney transplantation at Karolinska University Hospital
Who cannot join
- Absence of informed consent
- Allergy to leflunomide
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read more
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.
- Conditions
- Terminal Renal Failure, BK Virus Infection
- Being tested
- leflunomide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
leflunomideDrug
Screening: If BK viremia (BK PCR >10 000 copies/ml in serum) i. Reduced immunosuppression
- MMF / AZA withdrawal
- CNI reduction
- Tacrolimus 5 ng/ml in serum
- Cyclosporin 100 ng/ml in serum
- 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)
- Starting at 20 mgx1 PO daily
- 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
What is being measured
The primary outcome is the main question the study is designed to answer.
Renal function (serum creatinine)
Measured: 1 year after diagnosis of BK viremia
Secondary outcomes (1)
Incidence of BK virus associated nephropathy
Measured: 1 year after diagnosis of BK viremia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2008 (estimated)
- Study startMay 2007
- Primary completionMay 2009 (estimated)
- Study completionMay 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Terminal Renal FailureStudies of the same condition, open and under way.
- More trials run by Karolinska University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Uppsala University Hospital
- Investigators
- Lars Wennberg, MD, PhD, Principal investigator, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00684372
- Sponsor's protocol ID
- BK study
- Status last verified
- Feb 2009
- First submitted
- 21 May 2008
- Last updated
- 6 Feb 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BK Viremia After Renal Transplantation: Screening, Early Diagnosis, Early Reduction in Immunosuppression and Treatment With Leflunomide (Arava)
- ClinicalTrials.gov ID
- NCT00684372
- Acronym / sponsor ID
- BK study
- Conditions
- Terminal Renal Failure, BK Virus Infection
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Karolinska University HospitalUniversity, hospital or other
- Collaborators
- Uppsala University Hospital
- Study start
- May 2007
- Primary completion
- May 2009 (estimated)
- Study completion
- May 2009 (estimated)
- First posted
- 26 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All adult patients undergoing kidney transplantation at Karolinska University Hospital
Key exclusion criteria (3 listed)
- Absence of informed consent
- Allergy to leflunomide
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| leflunomideScreening: 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 | Drug | – |
Primary outcome
Renal function (serum creatinine)
Time frame: 1 year after diagnosis of BK viremia
1 secondary outcome
Incidence of BK virus associated nephropathy
Time frame: 1 year after diagnosis of BK viremia
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lars Wennberg, MD, PhD principal investigator
Karolinska University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing leflunomide in people with Terminal Renal Failure and BK Virus Infection, run by Karolinska University Hospital at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Feb 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Renal function (serum creatinine) (time frame: 1 year after diagnosis of BK viremia). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2009.