Ciprofloxacin for Prevention of BK Infection

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by The Methodist Hospital System
Sponsor:
Information provided by (Responsible Party):
Samir J. Patel, The Methodist Hospital System
ClinicalTrials.gov Identifier:
NCT01789203
First received: February 7, 2013
Last updated: June 24, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
BK Virus Infection
Drug: Ciprofloxacin
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Ciprofloxacin for Prevention of BK Infection in Renal Transplant Recipients

Resource links provided by NLM:


Further study details as provided by The Methodist Hospital System:

Primary Outcome Measures:
  • BK infection at 6 months post-transplant [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Proportion of patients 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:
  • Incidence of urinary tract infections as defined by a midstream urine sample containing 10^4 or more colony-forming units per mL [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Incidence of bacteremic infections at 6 months. Incidence of bacteremia as defined by a single positive blood culture that was not thought to be contaminated. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Incidence of quinolone-resistant bacterial infections [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Incidence of clostridium difficile infection [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Serious adverse events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Time to BK infection [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Proportion of patients developing BK infection at 1 year [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • First and peak plasma viral loads [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Incidence of acute rejection at 1 year [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Incidence and severity of BK nephropathy, as defined by positive staining of histopathological specimen, at 1 year [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Dose discontinuation due to adverse event related to therapy [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Serum creatinine concentrations at 1, 3, 6, 9, and 12 months post-transplant [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Graft loss at 1 year [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Death at 1 year [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 180
Study Start Date: January 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ciprofloxacin
Ciprofloxacin will be administered as two-250 mg capsules, administered once daily for 3 months post-transplant
Drug: Ciprofloxacin
Patients will be randomized 2:1 active comparator to placebo comparator.
Other Name: Cipro
Placebo Comparator: Placebo
Matching placebo will be administered as two-capsules given once daily for 3 months post-transplant
Drug: placebo

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects over the age of 18 years
  • Recipients of a primary renal allograft alone
  • 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 of pediatric en bloc kidney
  • 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
  • Any condition present during the initial transplant hospitalization that in the investigator's judgment would increase the risk associated with participation in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01789203

Contacts
Contact: Samir J Patel, Pharm.D. 713-441-2168 spatel2@houstonmethodist.org
Contact: Mary E Kueser, RN, BSN 713-441-6311 mekueser@houstonmethodist.org

Locations
United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Mary E Kueser, RN, BSN    713-441-6311    mekueser@houstonmethodist.org   
Sub-Investigator: A. Osama Gaber, MD         
Sub-Investigator: Richard J Knight, MD         
Sub-Investigator: Hemangshu Podder, MD         
Sub-Investigator: Jenny M DeVos, Pharm.D.         
Principal Investigator: Samir J Patel, Pharm.D.         
Sub-Investigator: Samantha Kuten, Pharm.D.         
Sub-Investigator: Jill Krisl, Pharm.D.         
Sponsors and Collaborators
The Methodist Hospital System
Investigators
Principal Investigator: Samir J Patel, Pharm.D. Clinical Pharmacist
  More Information

Publications:
Responsible Party: Samir J. Patel, Clinical Specialist II - Solid Organ Transplantation, The Methodist Hospital System
ClinicalTrials.gov Identifier: NCT01789203     History of Changes
Other Study ID Numbers: 0612-0114
Study First Received: February 7, 2013
Last Updated: June 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by The Methodist Hospital System:
BK infection
BK viremia
BK nephropathy
polyomavirus
fluoroquinolone
ciprofloxacin

Additional relevant MeSH terms:
Virus Diseases
Ciprofloxacin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 26, 2014