Quinolone Prophylaxis for the Prevention of BK Virus Infection in Kidney Transplantation: A Pilot Study

Study Overview
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Brief Summary
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Primary Research Questions: Efficacy, safety and feasibility of a 3-month course of levofloxacin in a pilot study will be assessed. Under efficacy, this pilot will determine whether levofloxacin can decrease the incidence of BK viruria and peak urine BK viral load. Under safety, this pilot will determine the incidence of adverse events with levofloxacin. Under feasibility, this pilot will determine the number of kidney transplant patients randomized over an eight month enrolment period, adherence to the levofloxacin and frequency of patient drop-out and loss to follow-up

Detailed Description
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BK virus infection has emerged as a major complication in renal transplantation leading to a significant reduction in graft survival. There are currently no proven strategies to prevent or treat BK virus infection. Quinolone antibiotics, such as levofloxacin, have demonstrated activity against BK virus. The investigators hypothesize that administration of a quinolone antibiotic, when given early post-transplantation, will prevent the establishment of BK viral replication in the urine and thus prevent systemic BK virus infection. A non-randomized study in kidney transplant recipients found that patients given levofloxacin or ciprofloxacin had a significantly lower incidence of BK viremia compared to those not receiving a quinolone (4% versus 24.5%, P=0.02). Objective: The primary objective of the full trial will be to determine if the quinolone levofloxacin decreases the occurrence of doubling creatinine, transplant failure or death in kidney transplant recipients. The aim of this pilot trial is to assess the efficacy, safety and feasibility of a 3-month course of levofloxacin in the kidney transplant population. Results from this pilot study will provide vital information to design and conduct a large, multi-centre trial to determine if quinolone therapy decreases meaningful clinical outcomes in kidney transplantation. If levofloxacin significantly reduces BK viruria and urine viral loads in kidney transplantation it will provide important justification of biologic effect to progress to the larger trial. If the full trial shows that levofloxacin significantly reduces BK infection and improves outcomes, its use in renal transplantation will be strongly endorsed given the lack of proven therapies for this condition.

Official Title
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Quinolone Prophylaxis for the Prevention of BK Virus Infection in Kidney Transplantation: A Pilot Study

Conditions
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Disease Due to BK Polyomavirus, Kidney Transplant Infection

Intervention / Treatment
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* Drug: Levofloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a primary or repeat kidney transplant recipient (deceased or living donor) age greater or equal to 18 years Exclusion Criteria: Unable to provide informed consent Greater than 5 days post-transplantation BK virus nephropathy with a previous transplant History of allergic reaction to any quinolone antibiotic History of quinolone associated tendonitis or tendon rupture Corrected QT interval prolongation on EKG as defined by Al-Khatib Concomitant use of medication known to prolong the QT interval such as class IA antiarrhythmic drugs (e.g. quinidine, procainamide, disopyramide), class III antiarrhythmic drugs (e.g. amiodarone, sotalol), azole antifungals (e.g. fluconazole) or macrolide antibiotics (e.g. erythromycin) Pregnant or breastfeeding as safety of levofloxacin not established Requires quinolone antibiotic for more than 14 days (e.g. for UTI prophylaxis) Recipient of a multi-organ transplant (e.g. kidney-pancreas) Currently enrolled in another interventional trial Previously enrolled in this study History of rhabdomyolysis Significant allergic reaction to ≥ 3 classes of antibiotics as these patients may have no other option other than quinolones for routine infection.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: sugar pill<br> | Drug: Levofloxacin<br>* 500mg, PO, once daily for 3 months<br>* Other names: DIN 02284707;|
| Active Comparator: levofloxacin<br> | Drug: Levofloxacin<br>* 500mg, PO, once daily for 3 months<br>* Other names: DIN 02284707;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: The time to occurence of BK viruria | BK viruria will be defined as ≥1000 copies/mL ok BK virus DNA in the urine. | 12 months post-transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Incidence and type of all adverse events | 12 months | 
| Acute rejection | Incidence of Acute rejection | 12 months | 
| Clostridium difficile associated diarrhea | Incidence of microbiologically confirmed clostridium difficile associated diarrhea | 12 months | 
| Infections | Incidence of other infections (viral, bacterial and fungal) based on established guidelines | 12 months | 
| Quinolone resistance | Incidence of quinolone resistance where a quinolone would have been a therapeutic option | 12 months | 
| Effect of levofloxacin on immunosuppressive drug doses and blood levels |  | 12 months | 
| Transplant failure |  | 12 months | 
| Mortality |  | 12 months | 
| Number of patients transplanted | Number of patients transplanted during the 8 month recruitment period who are randomized into the trial | 12 months | 
| Adherence | Proportion of randomized participants who are adherent to the protocol. | 12 months | 
| Use of quinolones | Use of quinolones outside of the protocol | 12 months | 
| Proportion of patient drop-out and loss to follow-up |  | 12 months | 
| Quantitative BK urine viral load |  | 12 months | 
| BK viremia | Time to occurence of BK viremia, defined as ≥250 copies/mL of BK virus DNA in the plasma | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Transplant, BK Polyomavirus Infection