Prediction and Prevention of Bloodstream Infections After Kidney Transplantation - The PREDICT Study
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 180
- 试验地点
- 3
- 主要终点
- Enterobacterales Urinary Tract Infections and/or Enterobacterales Bloodstream Infections
研究概览
简要总结
Kidney transplant recipients take medicines that suppress the immune system to prevent rejection of the transplanted kidney. As a result, they have a high risk of infections, especially urinary tract infections (UTIs). Some of these infections can spread to the bloodstream and cause serious illness, hospitalization, loss of kidney function, or death. Currently, there is no established strategy to prevent these serious bacterial infections in kidney transplant recipients who are at highest risk.
The PREDICT study is investigating whether a low daily dose of the antibiotic pivmecillinam can reduce the risk of bacterial urinary tract infections and bloodstream infections after kidney transplantation. The study focuses on kidney transplant recipients who have bacteria detected in their urine during the first month after transplantation, as previous research suggests that these patients have a particularly high risk of developing serious infections later.
In this randomized, double-blind, placebo-controlled trial, 180 adult kidney transplant recipients will be assigned by chance to receive either pivmecillinam or a matching placebo from 1 to 6 months after transplantation. Neither participants nor study staff will know which treatment has been assigned during the study. All participants will continue to receive standard post-transplant care and monitoring.
The main goal of the study is to determine whether prophylactic pivmecillinam can reduce the occurrence of infections caused by Enterobacterales bacteria, including urinary tract infections and bloodstream infections, during the first 6 months after transplantation. The study will also evaluate the effects of treatment on serious clinical outcomes, safety, quality of life, antimicrobial resistance, and long-term kidney transplant outcomes.
The study hypothesis is that targeted antibiotic prophylaxis with pivmecillinam in kidney transplant recipients at increased risk of infection will reduce the incidence of Enterobacterales urinary tract infections and bloodstream infections during the high-risk period after transplantation compared with placebo.
详细描述
Background:
Kidney transplant recipients are at increased risk of infectious complications because immunosuppressive treatment is required to prevent rejection of the transplanted kidney. Urinary tract infections are among the most common infectious complications after transplantation and may lead to bloodstream infections, which are associated with substantial morbidity, mortality, and risk of graft loss. Despite this burden, there is currently no established targeted strategy to prevent serious bacterial infections in kidney transplant recipients at highest risk of infection.
Previous work by the investigators demonstrated that bacteriuria during the first month after kidney transplantation is an important predictor of subsequent urinary tract infections and bloodstream infections. Early bacteriuria therefore represents a clinically useful marker for identifying a high-risk subgroup that may benefit from preventive interventions.
Study rationale:
The PREDICT study evaluates a risk-stratified prophylactic strategy using pivmecillinam in kidney transplant recipients with early bacteriuria. Pivmecillinam is a narrow-spectrum oral antibiotic with activity against Enterobacterales, which are the predominant causes of urinary tract infections and bloodstream infections after kidney transplantation. Its pharmacological profile and extensive clinical experience make it a potential candidate for targeted prevention during the period of highest infection risk after transplantation.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age ≥18 years.
- •Kidney transplant recipient.
- •Able to provide written informed consent.
- •≥1 urine sample with bacteriuria ≥10^5 CFU/mL (excluding fungi) within first month post-transplantation.
排除标准
- •Known strictures in the esophagus and/or obstructions in the gastrointestinal tract including diabetes gastroparesis.
- •Known hypersensitivity or allergy to β-lactam antibiotics.
- •Known or suspected genetic metabolism anomalies in the carnitine metabolism, including carnitine transporter defect or organic acidurias such as methylmalonic aciduria or propionic acidaemia.
- •Individuals of Faroese descent (defined as both biological parents born in the Faroe Islands).
- •Current treatment with valproic acid, valproate or other medications liberating pivalic acid.
- •Current treatment with probenecid.
- •Current treatment with methotrexate.
- •Ongoing dialysis one month post-transplantation.
- •Pregnancy or breastfeeding.
研究组 & 干预措施
Placebo
The placebo group (n = 90) will receive inactive placebo once daily from months 1-6 post-transplantation.
干预措施: Placebo (Drug)
Pivmecillinam
The intervention group (n = 90) will receive pivmecillinam 400 mg once daily from months 1-6 post-transplantation
干预措施: Pivmecillinam (Drug)
结局指标
主要结局
Enterobacterales Urinary Tract Infections and/or Enterobacterales Bloodstream Infections
时间窗: Months 1-6 post-transplantation
Cumulative incidence of participants experiencing at least one Enterobacterales urinary tract infection and/or Enterobacterales bloodstream infection during months 1-6 post-transplantation, i.e., composite endpoint.
Enterobacterales bloodstream infections
时间窗: The first 1-6 months post-transplantation
Proportion of participants with one or more Enterobacterales bloodstream infections during the first 6-12 month post-transplantation in the treatment arm vs. the placebo arm. Scale numeric from 0-100% (higher proportion is worser)
次要结局
- Time to Enterobacterales Bloodstream Infection(Months 1-6 post-transplantation)
- Time to All-Cause Mortality(Months 1-6 post-transplantation)
- Time to First Hospital Admission(Months 1-6 post-transplantation)
- Time to Graft Loss(Months 1-6 post-transplantation)
- Time to ≥50% Decrease in eGFR From Baseline(Months 1-6 post-transplantation)
- Number of Enterobacterales Urinary Tract Infections(Months 1-6 post-transplantation)
- Number of All Urinary Tract Infections(Months 1-6 post-transplantation)
- Number of All Bloodstream Infections(Months 1-6 post-transplantation)
- Participants Experiencing at Least One Serious Adverse Event and/or Adverse Event of Interest(Months 1-6 post-transplantation)
- Participants Experiencing at Least One Multidrug-Resistant Organism Infection(Months 1-6 post-transplantation)
- Number of Multidrug-Resistant Organism Infections(Months 1-6 post-transplantation)
- Participants Experiencing at Least One Clostridioides difficile Infection(Months 1-6 post-transplantation)
- Patient-reported quality of life(Months 1-6 post-transplantation)
- Severe outcome(The first 1-6 months post-transplantation)
- Infectious outcomes(The first 1-6 months post-transplantation)
- Outcomes related to the use of antibiotics(The first 1-6 months post-transplantation)
- Serious adverse events(The first 1-6 months post-transplantation)
- Patient-related outcomes(The first 1-6 months post-transplantation)
研究者
Susanne Dam Nielsen, MD, DMSc
Professor, Chief Physician
Rigshospitalet, Denmark