Clinical trial NCT05597540: Efficacy of 7 Days Versus 14 Days of Antibiotic Therapy for Acute Pyelonephritis in Kidney Transplant Recipients, a Multicentre Randomized Non-inferiority Trial.
Official title: Efficacy of 7 Days Versus 14 Days of Antibiotic Therapy for Acute Pyelonephritis in Kidney Transplant Recipients, a Multicentre Randomized Non-inferiority Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Pyelonephritis Acute
Kidney Transplant Infection
Keywords: antibiotic therapy
duration of antibiotic treatment reduction
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2022-10-28
Enrollment: 470
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Infections are a major cause of morbidity and mortality in solid organ transplant recipients. In kidney transplant recipients (KTR) urinary tract infection (UTI) represent 45-72% of all infections, and 30% of all hospitalizations for sepsis. Acute transplant pyelonephritis are the most common complications occurring in more than 20% of patients, mainly in the first year after transplantation. They are associated with an increased risk of acute kidney rejection and long-term kidney graft dysfunction. Gram-negative bacteria, mainly E. coli, account for more than 70% of UTI in KTR. As those infections are favoured by urinary tract modifications/defects and immunosuppression, they are often recurrent and necessitate repeated courses of antibiotics. Selective pressure due to antibiotic consumption, along with frequent hospital admissions and immunosuppression, are well known risk factors for the development of antibiotic resistant infections. Multidrug (MDR)- or extensively (XDR)- drug resistant Enterobacteriaceae including ESBL- or carbapenemase-producing organisms, are thus increasingly observed in transplant units and represent a global threat as very few new antibiotics are expected in the next decade.

One main strategy to limit antimicrobial resistance is to reduce the duration of antibiotic treatment. A 7 day-course is recommended for simple acute pyelonephritis (APN) treated with fluoroquinolones or parenteral B-lactams, prolonged up to 10 or 14 days in the presence of underlying disease at risk of complications. Most KT teams treat patients between 14-21 days as recommended by American guidelines. However, the need to extend treatment duration in immunosuppressed patients is a poorly defined concept and the optimal duration of treatment for APN in KTR is not known as these patients are excluded from most studies.

As there is an urgent need to reduce antibiotic consumption in this population at high risk of developing infections due to resistant pathogens, the hypothesis is that a 7 day-treatment is sufficient to cure APN with good clinical response after 48h of treatment in KTR and is as effective as 14 days.


Eligibility criteria: Inclusion Criteria:

* Age \>18 years KTR
* APN defined by: fever (T°≥38°C) (with or without clinical signs and/or symptoms of UTI) and pyuria (≥10\^4 white blood cells/mL or ≥10/mm3) and positive urine culture (uropathogen ≥10\^3 CFU/mL susceptible to the empirically administrated antibiotic)
* No confirmed or suspected febrile non urinary bacterial infection
* No urologic/renal complication at baseline imaging (abscess, obstruction...)
* Favourable early response to antibiotic treatment:48 to 60 hours after the first dose of antibiotic effective against the causative uropathogen) defined by: T°\<38°C and improvement (or resolution) of signs and/or symptoms of urinary tract infection if present at diagnosis
* Written informed consent

Exclusion Criteria:

* Severe or complicated condition

  * Any rapidly progressing disease or immediately life-threatening illness, including, but not limited to, septic shock, current or impeding respiratory failure, acute heart or liver failure
  * Admission or stay in intensive care unit at baseline
  * Obstruction of the urinary tract
  * Renal, perinephric or prostatic abscess
* Prior inclusion in this study
* Current participation to another interventional study
* Dual antibiotic therapy (prophylactic antibiotic such as cotrimoxazole allowed) (only 1 dose of aminoside is allowed before randomization)
* First month post transplantation
* Current indwelling catheter (including bladder catheter, ureteral stents, percutaneous nephrostomy tubes)
* Neurogenic bladder
* Enterocystoplasty
* Immunodeficiency or immunosuppressive therapy not related to kidney transplantation including hematologic malignancy, cancer, asplenia, neutropenia\<500 neutrophils/mm3
* Pregnancy, breastfeeding
* Hypersensitivity or previous severe adverse drug reaction to the antibiotic therapy
* Unable or unwilling, in the judgment of the investigator, to comply with the protocol
* Life expectancy\<1 month
* Patient under legal guardianship or without healthcare coverage
* Homeless patient
* Women with childbearing potential not using adequate contraception

Primary outcomes:
measure: Clinical cure day 30
timeFrame: at day 30
Secondary outcomes:
measure: Clinical cure day 90
timeFrame: at day 90
measure: Clinical cure day 180
timeFrame: at day 180
measure: Microbiological cure day 30
timeFrame: at day 30
measure: Microbiological cure day 90
timeFrame: at day 90
measure: Microbiological cure day 180
timeFrame: at day 180
measure: Incidence of relapse/recurrence day 30
timeFrame: at day 30
measure: Incidence of relapse/recurrence day 90
timeFrame: at day 90
measure: Incidence of adverse event
timeFrame: at day 180
measure: Kidney function
timeFrame: at day 90
measure: Kidney function
timeFrame: at day 180
measure: Hospital length of stay
timeFrame: Up to day 180
measure: Antibiotic consumption
timeFrame: Up to day 180
measure: Rectal carriage
timeFrame: at inclusion
measure: Rectal carriage
timeFrame: at day 30
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Boulogne-Billancourt
country: France
facility: Hôpital Foch
city: Créteil
country: France
facility: CHU Mondor
city: Lyon
country: France
facility: CHU Lyon
city: Nantes
country: France
facility: CHU Nantes
city: Paris
country: France
facility: CHU Kremlin-Bicêtre
city: Paris
country: France
facility: CHU Necker
city: Paris
country: France
facility: CHU Saint Louis
city: Toulouse
country: France
facility: CHU Toulouse
Study officials:
References: