Ciprofloxacin for Prevention of BK Infection

NCT01789203 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: Pro00007510IRB0612-0114
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

BK Virus Infection

Keywords

BK infection; BK viremia; BK nephropathy; polyomavirus; fluoroquinolone; ciprofloxacin

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (9)

• Number of Patients With Gram Negative Urinary Tract Infections at 6 Months

  6 months

• Number of Patients With Bacteremia at 6 Months

  6 months

• Number of Patients With Quinolone-resistant Infection at 6 Months

  6 months

• Clostridium Difficile at 6 Months

  6 months

• Serious Adverse Events

  4 months

Other Outcomes (2)

• Graft Loss at 1 Year

  12 months

• Death at 1 Year

  12 months

Study Arms (2)

Ciprofloxacin

ACTIVE COMPARATOR

Ciprofloxacin will be administered as two-250 mg capsules, administered once daily for 3 months post-transplant

Drug: Ciprofloxacin

Placebo

PLACEBO COMPARATOR

Matching placebo will be administered as two-capsules given once daily for 3 months post-transplant

Drug: placebo

Interventions

Ciprofloxacin DRUG

Patients will be randomized 2:1 active comparator, Cipro, to placebo comparator.

Also known as: Cipro

Ciprofloxacin

placebo DRUG

Patients will be randomized 2:1 placebo comparator to active comparator, Cipro.

Also known as: inactive drug, innocuous medication

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Related Publications (7)

• 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.

  PMID: 15707414 BACKGROUND

• 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.

  PMID: 17503741 BACKGROUND

• 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.

  PMID: 15712075 BACKGROUND

• 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.

  PMID: 21185389 BACKGROUND

• 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.

  PMID: 20507960 BACKGROUND

• Wajih Z, Karpe KM, Walters GD. Interventions for BK virus infection in kidney transplant recipients. Cochrane Database Syst Rev. 2024 Oct 9;10(10):CD013344. doi: 10.1002/14651858.CD013344.pub2.

  PMID: 39382091 DERIVED

• 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.

  PMID: 30811872 DERIVED

MeSH Terms

Interventions

Ciprofloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Samir Patel
• Organization: Methodist Hospital

spatel2@houstonmethodist.org

267-808-0577

Study Officials

• Samir J Patel, Pharm.D.

  Clinical Pharmacist

  STUDY CHAIR

• Ahmed O Gaber, MD

  Director, Houston Methodist Transplant Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Houston Methodist Transplant Center

Study Record Dates

• First Submitted: February 7, 2013
• First Posted: February 12, 2013
• Study Start: January 1, 2013
• Primary Completion: April 1, 2017
• Study Completion: October 1, 2017
• Last Updated: November 13, 2019
• Results First Posted: November 13, 2019

Record last verified: 2019-10

Locations

US (1)