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.
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.
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).
Parallel
Pivmecillinam
DrugStudy participants in the intervention arm will receive 400 mg pivmecillinam tablets once daily administered orally. Treatment will be initiated one month post-transplantation and will continue for a total duration of 5 months (months 1-6 post-transplantation).
Placebo
DrugStudy participants in the placebo arm will receive one inactive placebo tablet once daily; the timing, frequency and duration is the same as for the active study drug.
Enterobacterales Urinary Tract Infections and/or Enterobacterales Bloodstream Infections
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.
Time to Enterobacterales Bloodstream Infection
Time to first occurrence of Enterobacterales bloodstream infection during months 1-6 post-transplantation
Time to All-Cause Mortality
Time to death of any cause during months 1-6 post-transplantation
Time to First Hospital Admission
Time to first hospital admission during months 1-6 post-transplantation
Time to Graft Loss
Time to graft loss during months 1-6 post-transplantation
Exploratory: Change in Gut and Urinary Microbiome Diversity
Change in microbial alpha diversity (richness, Shannon, Simpson, and Gini) and beta diversity from baseline (1 month post-transplantation) to 6 months post-transplantation.
Exploratory: Change in Gut and Urinary Resistome Diversity
Change in diversity of antibiotic resistance genes by type and subtype from baseline (1 month post-transplantation) to 6 months post-transplantation.
Exploratory: Immunological and Metabolic Biomarkers
Exploratory analyses of immunological and metabolic biomarkers measured in blood samples collected at baseline, 3 months, and 6 months post-transplantation to investigate potential associations with systemic inflammation, immune activation, and metabolic function.
Exploratory: Long-Term All-Cause Mortality
All-cause mortality determined at the 10-year registry follow-up
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Susanne Dam Nielsen, MD, DMSc
Lead sponsor
Rigshospitalet, Denmark
Sponsor institution
This trial is not recruiting at the moment. You can still explore other options:
