Clinical trial NCT01789203: Ciprofloxacin for Prevention of BK Infection
Official title: Ciprofloxacin for Prevention of BK Infection in Renal Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: BK Virus Infection
Keywords: BK infection
BK viremia
BK nephropathy
polyomavirus
fluoroquinolone
ciprofloxacin
Lead sponsor: The Methodist Hospital Research Institute
Sponsor class: OTHER
First posted: 2013-02-12
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients Developing BK Infection at 6 Months Post-transplant
timeFrame: 6 months
Secondary outcomes:
measure: Number of Patients With Gram Negative Urinary Tract Infections at 6 Months
timeFrame: 6 months
measure: Number of Patients With Bacteremia at 6 Months
timeFrame: 6 months
measure: Number of Patients With Quinolone-resistant Infection at 6 Months
timeFrame: 6 months
measure: Clostridium Difficile at 6 Months
timeFrame: 6 months
measure: Serious Adverse Events
timeFrame: 4 months
measure: Time to BK Infection
timeFrame: 12 months
measure: BK Viremia at 1 Year
timeFrame: 12 months
measure: First Plasma Viral Loads
timeFrame: 12 months
measure: Acute Rejection at 1 Year
timeFrame: 12 months
Other outcomes:
measure: Graft Loss at 1 Year
timeFrame: 12 months
measure: Death at 1 Year
timeFrame: 12 months
Locations:
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
Study officials:
affiliation: Clinical Pharmacist
name: Samir J Patel, Pharm.D.
role: STUDY_CHAIR
affiliation: Director, Houston Methodist Transplant Center
name: Ahmed O Gaber, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brennan DC, Agha I, Bohl DL, Schnitzler MA, Hardinger KL, Lockwood M, Torrence S, Schuessler R, Roby T, Gaudreault-Keener M, Storch GA. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant. 2005 Mar;5(3):582-94. doi: 10.1111/j.1600-6143.2005.00742.x.
citation: Ali SH, Chandraker A, DeCaprio JA. Inhibition of Simian virus 40 large T antigen helicase activity by fluoroquinolones. Antivir Ther. 2007;12(1):1-6.
citation: Leung AY, Chan MT, Yuen KY, Cheng VC, Chan KH, Wong CL, Liang R, Lie AK, Kwong YL. Ciprofloxacin decreased polyoma BK virus load in patients who underwent allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2005 Feb 15;40(4):528-37. doi: 10.1086/427291. Epub 2005 Jan 21.
citation: Miller AN, Glode A, Hogan KR, Schaub C, Kramer C, Stuart RK, Costa LJ. Efficacy and safety of ciprofloxacin for prophylaxis of polyomavirus BK virus-associated hemorrhagic cystitis in allogeneic hematopoietic stem cell transplantation recipients. Biol Blood Marrow Transplant. 2011 Aug;17(8):1176-81. doi: 10.1016/j.bbmt.2010.12.700. Epub 2010 Dec 23.
citation: Gabardi S, Waikar SS, Martin S, Roberts K, Chen J, Borgi L, Sheashaa H, Dyer C, Malek SK, Tullius SG, Vadivel N, Grafals M, Abdi R, Najafian N, Milford E, Chandraker A. Evaluation of fluoroquinolones for the prevention of BK viremia after renal transplantation. Clin J Am Soc Nephrol. 2010 Jul;5(7):1298-304. doi: 10.2215/CJN.08261109. Epub 2010 May 27.
citation: Patel SJ, Knight RJ, Kuten SA, Graviss EA, Nguyen DT, Moore LW, Musick WL, Gaber AO. Ciprofloxacin for BK viremia prophylaxis in kidney transplant recipients: Results of a prospective, double-blind, randomized, placebo-controlled trial. Am J Transplant. 2019 Jun;19(6):1831-1837. doi: 10.1111/ajt.15328. Epub 2019 Apr 4.