Efficacy of 7 Days Versus 14 Days of Antibiotic Therapy for Acute Pyelonephritis in Kidney Transplant Recipients, a Multicentre Randomized Non-inferiority Trial.

NCT05597540 | Recruiting Phase 3 DMC

• 1 other identifier: APHP200020
• Study Type: interventional
• Target: 470
• Locations: 1 country
• Sites: 9

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.

Conditions

Pyelonephritis Acute; Kidney Transplant Infection

Keywords

antibiotic therapy; duration of antibiotic treatment reduction

Outcome Measures

Primary Outcomes (1)

• Clinical cure day 30

  Clinical cure and no additional antibiotic treatment since the end of antibiotic treatment up to the main evaluation at day 30. Clinical cure is defined as fever \<38°C and no symptoms of Urinary Tract Infection (UTI).

  at day 30

Secondary Outcomes (14)

• Clinical cure day 90

  at day 90

• Clinical cure day 180

  at day 180

• Microbiological cure day 30

  at day 30

• Microbiological cure day 90

  at day 90

• Microbiological cure day 180

  at day 180

Study Arms (2)

7 day-duration antibiotic treatment

EXPERIMENTAL

Drug: Short antibiotic treatment

14 day-duration antibiotic treatment

ACTIVE COMPARATOR

Drug: Usual antibiotic treatment

Interventions

Short antibiotic treatment DRUG

7 day-duration antibiotic treatment. The choice of antibiotic treatment is left to the medical team in charge of the patient.

7 day-duration antibiotic treatment

Usual antibiotic treatment DRUG

14 day-duration antibiotic treatment. The choice of antibiotic treatment is left to the medical team in charge of the patient.

14 day-duration antibiotic treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (9)

CHU Bordeaux

Bordeaux, France

NOT YET RECRUITING

Hôpital Foch

Boulogne-Billancourt, France

NOT YET RECRUITING

CHU Mondor

Créteil, France

RECRUITING

CHU Lyon

Lyon, France

NOT YET RECRUITING

CHU Nantes

Nantes, France

RECRUITING

CHU Kremlin-Bicêtre

Paris, France

NOT YET RECRUITING

CHU Necker

Paris, France

RECRUITING

CHU Saint Louis

Paris, France

RECRUITING

CHU Toulouse

Toulouse, France

NOT YET RECRUITING

Central Study Contacts

Matthieu Lafaurie, MD

CONTACT

142494117; matthieu.lafaurie@aphp.fr

Jérôme Lambert, Pr

CONTACT

142499742; jerome.lambert@u-paris.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Randomized double blind trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2022
• First Posted: October 28, 2022
• Study Start: February 22, 2024
• Primary Completion (Estimated): March 22, 2027
• Study Completion (Estimated): August 22, 2027
• Last Updated: May 29, 2024

Record last verified: 2024-02

Locations

FR (9)