A Randomized Non-Inferiority Study Comparing 7-Day versus 14-Day Antibiotic Treatment with Ciprofloxacin or Ceftriaxone for Graft Pyelonephritis in Kidney Transplant Recipients

The primary objective of this study is to demonstrate the non-inferiority of a 7-day antibiotic treatment regimen compared to the standard 14-day regimen in patients presenting with graft pyelonephritis. This evaluation aims to determine if a shorter therapeutic duration provides equivalent clinical efficacy for kidney transplant recipients.

Secondary objectives include the assessment of the following outcomes:

• Mortality rates.
• Recurrence of infection.
• Readmission rates.
• Total duration of hospitalization, intravenous therapy, and overall antibiotic treatment.
• Safety parameters, including potential interactions with immunosuppression, catheter-related adverse effects such as phlebitis, and episodes of Clostridioides difficile infection.
• Evolution of renal function.
• Incidence of graft rejection or graft loss.
• Antibiotic susceptibility of microorganisms identified via urinary tract infection episodes and follow-up urine cultures.

The sponsor did not provide information regarding the total number of participants. The study population consists of adult kidney transplant recipients of both sexes. Inclusion requires a diagnosis of acute graft pyelonephritis occurring between the time of transplantation and 48 hours after the initiation of antibiotic treatment. Participants must be able to provide written informed consent.

This prospective, multicenter, randomized, non-inferiority study compares a 7-day antibiotic treatment regimen against a 14-day regimen for the management of graft pyelonephritis in kidney transplant recipients. The trial design involves the administration of either ciprofloxacin or ceftriaxone as test or comparator treatments. Following a screening period to identify eligible adult patients experiencing an acute episode, participants are assigned to a treatment group. The primary endpoint is evaluated at 90 days post-inclusion and includes all-cause mortality, recurrence of infection, or hospital readmission. Secondary endpoints involve the assessment of renal function, adverse events, Clostridioides difficile episodes, and graft loss. Monitoring occurs through follow-up assessments at 30 and 90 days to evaluate renal evolution and urine cultures. The total duration of participant involvement is centered around a 90-day follow-up period following inclusion.

The investigational treatment involving ciprofloxacin hydrochloride and ciprofloxacin is administered in the pharmaceutical form PHF00134MIG. The dosage is 1 g via the intravenous route.

The investigational treatment involving ceftriaxone sodium and lidocaine hydrochloride is administered in the pharmaceutical form PHF00231MIG. The dosage is 1 g via the intravenous route.

The comparator treatment involving ceftriaxone is administered at a dosage of 1 g via the intravenous route.

The comparator treatment involving ciprofloxacin is administered at a dosage of 500 mg via the oral route.

The primary efficacy assessment is based on a composite endpoint evaluated at 90 days following inclusion. This endpoint includes all-cause mortality, recurrence of graft pyelonephritis, or hospital readmission for any cause following discharge related to the pyelonephritis episode.

Secondary efficacy and safety parameters include:

• Total duration of antibiotic therapy and total duration of intravenous antibiotic administration from the time of diagnosis.
• Total length of hospitalization from the time of diagnosis.
• Incidence of adverse events and interactions with concomitant treatments during hospitalization and up to 90 days post-inclusion.
• Frequency of catheter-related adverse events during admission and up to 90 days post-inclusion.
• Episodes of Clostridioides difficile at 90 days post-inclusion.
• Evolution of renal function at 90 days post-inclusion.
• Incidence of rejection and graft loss within 90 days post-inclusion.
• Identification of isolated microorganisms and antibiotic sensitivity via urine cultures at 30 and 90 days post-inclusion.