Prediction and Prevention of Bloodstream Infections After Kidney Transplantation

ConditionsKidney Transplant Infection Bloodstream Infection

Trial statusNot yet recruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorSusanne Dam Nielsen, MD, DMSc

About this trial

Background: Kidney transplant (KTx) recipients receive life-long immunosuppression, which increases the risk of severe infections. Bloodstream infections (BSI) are common after transplantation and are associated with high mortality and morbidity. Prophylactic antibiotic treatment of all KTx recipients does not provide overall benefit, but a personalized strategy of prophylactic treatment of KTx recipients at high risk of BSI with targeted antibiotics has not been assessed.

Primary aim: To determine if prophylactic pivmecillinam in high-risk KTx recipients decreases the incidence of Enterobacterales BSI in the first 1-6 months post-transplantation.

Secondary aim: To assess if prophylactic pivmecillinam reduces all-cause mortality, hospital admissions, graft loss, changes in the gut and urine resistome and microbiome, and increases quality of life in high-risk KTx recipients.

Design and target group: Multi-center double-blinded randomized controlled trial of 150 KTx recipients at high risk of BSI who will be randomized 1:1 to either pivmecillinam 400 mg once daily or placebo from months 1-6 post-transplantation. KTx recipients will be included from Rigshospitalet, Aarhus University Hospital and Odense University Hospital. 60 participants in each study arm will provide urine and stool samples at randomization and at the end of intervention for metagenomic sequencing of the bacterial microbiome and resistome.

Perspectives: This trial will provide evidence necessary to assess if KTx recipients at high risk of BSI benefit from targeted prophylactic antibiotics and address a critical knowledge gap of how to reduce mortality and morbidity due to BSI after KTx. The study will also serve as proof-of-concept for a personalized approach to infection prevention in other populations at high risk of severe infections.

Results from the study may easily be implemented since there is already a clinical set-up for prevention of viral infections in KTx recipients.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Adult (>18 years) KTx recipients at high risk of BSI in the first year post-KTx.

Disqualifiers

Recipients who cannot give informed consent or have contraindications for pivmecillinam treatment, including allergy to beta-lactamase antibiotics.

Trial design

Design model

Parallel

Treatments tested in this trial

Pivmecillinam
Drug
The intervention group will receive pivmecillinam 400 mg once daily from months 1-6 post-transplantation.
Placebo
Drug
The control group (n=75) will receive placebo once daily from months 1-6 post-transplantation.

Treatment groups

150 Participants

are divided into 2 treatment groups

Group A: InterventionActive comparator 1 intervention

Group B: ControlPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

Enterobacterales bloodstream infections

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)

Time frame