Ciprofloxacin for Prevention of BK Infection in Renal Transplant Recipients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Number of Patients Developing BK Infection at 6 Months Post-transplant
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Ciprofloxacin
Ciprofloxacin will be administered as two-250 mg capsules, administered once daily for 3 months post-transplant
干预措施: Ciprofloxacin (Drug)
Placebo
Matching placebo will be administered as two-capsules given once daily for 3 months post-transplant
干预措施: placebo (Drug)
结局指标
主要结局
Number of Patients Developing BK Infection at 6 Months Post-transplant
时间窗: 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.
次要结局
- Number of Patients With Quinolone-resistant Infection at 6 Months(6 months)
- Number of Patients With Bacteremia at 6 Months(6 months)
- Clostridium Difficile at 6 Months(6 months)
- Serious Adverse Events(4 months)
- Time to BK Infection(12 months)
- BK Viremia at 1 Year(12 months)
- Acute Rejection at 1 Year(12 months)
- Number of Patients With Gram Negative Urinary Tract Infections at 6 Months(6 months)
- First Plasma Viral Loads(12 months)
研究者
Ahmed Osama Gaber, MD
Director, Houston Methodist Transplant Center
The Methodist Hospital Research Institute