BK infection is an important cause of graft dysfunction and graft loss after renal transplantation. It has been widely accepted that emergence of BK virus correlates with the more potent immunosuppressive agents used to lower acute rejection rates. In contrast to other opportunistic infections after transplantation, for which routine prophylactic agents are administered, there is no effective agent for the prevention of BK infection. Some data, however, suggests that quinolone antibiotics such as ciprofloxacin may have activity against BK virus. This has led us to investigate whether routine, short-term ciprofloxacin administration post-transplant can lower the incidence of BK infection.
BK virus is a member of the virus family polyomaviridae ("polyoma"). The virus, which can manifest as a viral nephritis, was first described in a renal transplant recipient in 1971, however it was not until the past decade that infection with BK virus became known as an important contributor to graft dysfunction and graft loss after renal transplantation. It has been widely accepted that emergence of BK virus correlates with the more potent immunosuppressive agents currently used to lower acute rejection rates. In contrast to other opportunistic infections after transplantation, for which routine prophylactic agents are administered, there is no effective agent for the prevention of BK infection, nor is there an effective agent for treating BK infection once it occurs. Ciprofloxacin is a well known anti-infective agent in the fluoroquinolone class of antibiotics. It is most active against gram-negative enteric pathogens, and is commonly used for a variety of infectious indications. Though classified as antibacterial agents, fluoroquinolones have been suggested to exhibit anti-BK viral effects by interfering with helicase activity of the BK virus large T antigen. Ciprofloxacin has been shown in previous studies to reduce urine BK viral load, and BK-associated hemorrhagic cystitis in the stem cell transplant population. Ciprofloxacin has also been associated with a lower incidence of BK viremia in one retrospective study in kidney transplant recipients. Based on these reports, the investigators hope to find a reduction BK viremia and BK nephropathy using a prospective, randomized study design.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
200
Patients will be randomized 2:1 active comparator, Cipro, to placebo comparator.
Patients will be randomized 2:1 placebo comparator to active comparator, Cipro.
Houston Methodist Hospital
Houston, Texas, United States
Number of Patients Developing BK Infection at 6 Months Post-transplant
Number of patients (followed by proportion) developing BK infection at 6 months post-transplant. BK infection is defined as the presence of a detectable BK viral load in plasma by polymerase chain reaction (PCR), or the presence of BK viral inclusions on kidney biopsy specimens.
Time frame: 6 months
Number of Patients With Gram Negative Urinary Tract Infections at 6 Months
Number of patients with gram negative urinary tract infections as defined by a midstream urine sample containing 10\^4 or more colony-forming units per mL
Time frame: 6 months
Number of Patients With Bacteremia at 6 Months
Number of patients with bacteremic infection at 6 months. Bacteremia defined by a single positive blood culture that was not thought to be contaminated.
Time frame: 6 months
Number of Patients With Quinolone-resistant Infection at 6 Months
Number of patients with quinolone-resistant gram negative bacterial infections, among those with a gram-negative infection
Time frame: 6 months
Clostridium Difficile at 6 Months
Clostridium difficile infection at 6 months
Time frame: 6 months
Serious Adverse Events
Serious adverse events collected for up to 4 months (3 months on study drug plus 1 additional month)
Time frame: 4 months
Time to BK Infection
Median time to initial BK viremia episode, days
Time frame: 12 months
BK Viremia at 1 Year
Proportion of patients developing BK viremia at 1 year
Time frame: 12 months
First Plasma Viral Loads
First BK plasma viral loads
Time frame: 12 months
Acute Rejection at 1 Year
Number of patients with biopsy-proven acute rejection of the allograft at 1 year, based on Banff classification
Time frame: 12 months
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