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

• Efficacy: The time to occurence of BK viruria [ Time Frame: 12 months post-transplantation ] [ Designated as safety issue: No ]
  BK viruria will be defined as ≥1000 copies/mL ok BK virus DNA in the urine.
  
  

• Adverse Events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  Incidence and type of all adverse events
  
  
• Acute rejection [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  Incidence of Acute rejection
  
  
• Clostridium difficile associated diarrhea [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  Incidence of microbiologically confirmed clostridium difficile associated diarrhea
  
  
• Infections [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  Incidence of other infections (viral, bacterial and fungal) based on established guidelines
  
  
• Quinolone resistance [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  Incidence of quinolone resistance where a quinolone would have been a therapeutic option
  
  
• Effect of levofloxacin on immunosuppressive drug doses and blood levels [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  
• Transplant failure [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  
• Mortality [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  
• Number of patients transplanted [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Number of patients transplanted during the 8 month recruitment period who are randomized into the trial
  
  
• Adherence [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Proportion of randomized participants who are adherent to the protocol.
  
  
• Use of quinolones [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Use of quinolones outside of the protocol
  
  
• Proportion of patient drop-out and loss to follow-up [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  
• Quantitative BK urine viral load [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  
• BK viremia [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Time to occurence of BK viremia, defined as ≥250 copies/mL of BK virus DNA in the plasma
  
  

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.