Ciprofloxacin for Prevention of BK Infection

Phase 4

Completed

Conditions: BK Virus Infection

Interventions: Drug: placebo
Drug: Ciprofloxacin

Registration Number: NCT01789203

Lead Sponsor: The Methodist Hospital Research Institute

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 200

Inclusion Criteria

Male or female subjects over the age of 18 years
Recipients of a primary or repeat renal allograft either alone (from a deceased or living donor) or as a dual-kidney transplant
Signed informed consent form prior to any research assessment

Exclusion Criteria

Patients with known severe allergy to ciprofloxacin
History of tendon rupture or tendinitis
Use of antiarrythmic drugs 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)
Patients with history of previous non-renal transplantation
Recipients administered rituximab within one year prior to transplantation, or recipients expected to receive rituximab as part of desensitization strategy or for the presence of historical donor specific antibodies
QTc interval interval of greater than 500 msec on admission or post-operative EKG
BK nephropathy with previous transplant
BK viremia on admission
Any condition present during the initial transplant hospitalization that in the investigator's judgment would increase the risk associated with participation in the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Matching placebo will be administered as two-capsules given once daily for 3 months post-transplant
Ciprofloxacin	Ciprofloxacin	Ciprofloxacin will be administered as two-250 mg capsules, administered once daily for 3 months post-transplant

Primary Outcome Measures

Name	Time	Method
Number of Patients Developing BK Infection at 6 Months Post-transplant	6 months	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.

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Quinolone-resistant Infection at 6 Months	6 months	Number of patients with quinolone-resistant gram negative bacterial infections, among those with a gram-negative infection
Number of Patients With Bacteremia at 6 Months	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.
Clostridium Difficile at 6 Months	6 months	Clostridium difficile infection at 6 months
Serious Adverse Events	4 months	Serious adverse events collected for up to 4 months (3 months on study drug plus 1 additional month)
Time to BK Infection	12 months	Median time to initial BK viremia episode, days
BK Viremia at 1 Year	12 months	Proportion of patients developing BK viremia at 1 year
Acute Rejection at 1 Year	12 months	Number of patients with biopsy-proven acute rejection of the allograft at 1 year, based on Banff classification
Number of Patients With Gram Negative Urinary Tract Infections at 6 Months	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
First Plasma Viral Loads	12 months	First BK plasma viral loads