Quinolone prophylaxis for the prevention of BK virus infection in kidney transplantation: study protocol for a randomized controlled trial

Abstract

BackgroundBK virus infection has emerged as a major complication in kidney 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. We 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.Methods/designThe 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. This is a multicenter, randomized, double-blind, placebo-controlled trial with two parallel arms conducted in 11 Canadian kidney transplant centers. A total of 154 patients with end-stage renal disease undergoing kidney transplantation will be randomized to receive a 3-month course of levofloxacin or placebo starting in the early post-transplant period. Levofloxacin will be administered at 500 mg po daily with dose adjustments based on kidney function. The primary outcome will be the time to occurrence of BK viruria within the first year post-transplantation. Secondary outcomes include BK viremia, measures of safety (adverse events, resistant infections,Clostridium difficile-associated diarrhea), measures of feasibility (proportion of transplanted patients recruited into the trial), proportion of patients adherent to the protocol, patient drop-out and loss to follow-up,and use of quinolone antibiotics outside of the trial protocol.DiscussionResults from this pilot study will provide vital information to design and conduct a large, multicenter trial to determine if quinolone therapy decreases clinically meaningful outcomes in kidney transplantation. If levofloxacin significantly reduces BK viruria and urine viral loads in kidney transplantation, it will provide important justification to progress to the larger trial. If the full trial shows that levofloxacin significantly reduces BK infection and improves outcomes, its use in kidney transplantation will be strongly endorsed given the lack of proven therapies for this condition.Trial registrationThis trial was funded by the Canadian Institutes of Health Research (grant number:222493) and is registered at ClinicalTrials.gov ( NCT01353339).

Levofloxacin for BK Virus Prophylaxis Following Kidney Transplantation

“…22 BK viruria was defined as 500 copies/mL or more of BK virus DNA in the urine. 16 BK virus infection was determined at each study visit by testing urine samples using quantitative real-time polymerase chain reaction for the detection of BK virus DNA at a central laboratory at the ary safety outcomes included the incidence and type of all adverse events including acute rejection, microbiologically confirmed Clostridium difficile-associated diarrhea, other infections (viral, bacterial, fungal), positive cultures with quinolone resistance, transplant failure, and mortality. Secondary clinical outcomes included quantitative BK viral load in urine and the occurrence of BK viremia (defined as ≥25 copies/mL of BK virus DNA in the plasma).…”

“…A detailed version of the trial design and methods has been published. 16 Eligible patients providing written informed consent were randomly assigned to receive either levofloxacin or placebo in a 1:1 fashion. Allocation was achieved through web-based central randomization in variable blocks stratified by center.…”

European perspective on human polyomavirus infection, replication and disease in solid organ transplantation

“…Interventions for BKPyV replication and PyVAN potentially encompass prophylactic, preemptive and therapeutic modalities. There are no BKPyV‐specific antiviral drugs for prophylaxis or treatment, but the use of fluoroquinolones such as ciprofloxacin and levofloxacin after kidney transplantation has been associated with a reduced frequency of BKPyV replication in limited retrospective studies and case series . The use of mTOR inhibitors has been associated with reduced BKPyV events in registry studies and in retrospective analyses, but a general recommendation must be balanced against the overall graft function and outcome .…”

Antiviral, antifungal, and antiparasitic activities of fluoroquinolones optimized for treatment of bacterial infections: a puzzling paradox or a logical consequence of their mode of action?

“…Therefore, a study protocol for a randomized controlled clinical trial evaluating the prophylactic efficacy of fluoroquinolones has been designed and is registered at ClinicalTrials.gov under NCT01353339; levofloxacin at a dose of 500 mg q.d. will be administered for 3 months and will be compared to placebo [66]. Another clinical study on the use of ciprofloxacin (250 mg q.d.…”