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NCT Number: NCT05597540

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

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.

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Key information

Conditions

Pyelonephritis Acute Kidney Transplant Infection

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

CHU Bordeaux, Bordeaux, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

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.

Primary outcomes

  1. Clinical cure day 30

    Time frame: at 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).

Secondary outcomes

  1. Clinical cure day 90

    Time frame: at day 90

    Clinical cure and no additional antibiotic treatment since the end of antibiotic treatment up to the main evaluation at day 90.

    Clinical cure is defined as fever <38°C and no symptoms of Urinary Tract Infection (UTI).

  2. Clinical cure day 180

    Time frame: at day 180

    Clinical cure and no additional antibiotic treatment since the end of antibiotic treatment up to the main evaluation at day 180.

    Clinical cure is defined as fever <38°C and no symptoms of Urinary Tract Infection (UTI).

  3. Microbiological cure day 30

    Time frame: at day 30

    Microbiological cure is defined as a sterile urine or uropathogene ≤ 10.3 CFU/mL in urine culture

  4. Microbiological cure day 90

    Time frame: at day 90

    Microbiological cure is defined as a sterile urine or uropathogene ≤ 10.3 CFU/mL in urine culture

  5. Microbiological cure day 180

    Time frame: at day 180

    Microbiological cure is defined as a sterile urine or uropathogene ≤ 10.3 CFU/mL in urine culture

  6. Incidence of relapse/recurrence day 30

    Time frame: at day 30

    Relapse or recurrence of the Urinary Tract Infection

  7. Incidence of relapse/recurrence day 90

    Time frame: at day 90

    Relapse or recurrence of the Urinary Tract Infection

  8. Incidence of adverse event

    Time frame: at day 180

    Incidence of adverse events imputable to antibiotic treatment

  9. Kidney function

    Time frame: at day 90

    Evaluated by MDRD or CKD

    MDRD : Modification of Diet in Renal Disease (MDRD) Study equation.

    Froissart M, Rossert J, Jacquot C, Paillard M, Houillier P. Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function. J Am Soc Nephrol 2005;16(3):763-73.

    CKD-EPI (Chronic Kidney Disease EPIdemiology collaboration, Levey, 2009)

    A New Equation to Estimate Glomerular Filtration Rate. Andrew S. Levey, MD; Lesley A. Stevens, MD, MS; Christopher H. Schmid, PhD; Yaping (Lucy) Zhang, MS; Alejandro F. Castro III, MPH; Harold I. Feldman, MD, MSCE; John W. Kusek, PhD; Paul Eggers, PhD; Frederick Van Lente, PhD; Tom Greene, PhD; and Josef Coresh, MD, PhD, MHS, for the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). Annals of Internal Medicine 2009;150(9):604-613

  10. Kidney function

    Time frame: at day 180

    Evaluated by MDRD or CKD

    MDRD : Modification of Diet in Renal Disease (MDRD) Study equation.

    Froissart M, Rossert J, Jacquot C, Paillard M, Houillier P. Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function. J Am Soc Nephrol 2005;16(3):763-73.

    CKD-EPI (Chronic Kidney Disease EPIdemiology collaboration, Levey, 2009)

    A New Equation to Estimate Glomerular Filtration Rate. Andrew S. Levey, MD; Lesley A. Stevens, MD, MS; Christopher H. Schmid, PhD; Yaping (Lucy) Zhang, MS; Alejandro F. Castro III, MPH; Harold I. Feldman, MD, MSCE; John W. Kusek, PhD; Paul Eggers, PhD; Frederick Van Lente, PhD; Tom Greene, PhD; and Josef Coresh, MD, PhD, MHS, for the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). Annals of Internal Medicine 2009;150(9):604-613

  11. Hospital length of stay

    Time frame: Up to day 180

    Hospitalisation length stay defined by the delay between the date of inclusion and the date of hospital discharge

  12. Antibiotic consumption

    Time frame: Up to day 180

    Antibiotic consumption (indication, dose and duration) throughout the follow-up will be recorded.

  13. Rectal carriage

    Time frame: at inclusion

    Rectal carriage of antibiotic resistant Enterobacteriaceae

  14. Rectal carriage

    Time frame: at day 30

    Rectal carriage of antibiotic resistant Enterobacteriaceae

Study contacts

Contact information is provided by the study sponsor or research team.

Jérôme Lambert, Pr

CONTACT

[email protected]

142499742 ext. +33

Matthieu Lafaurie, MD

CONTACT

[email protected]

142494117 ext. +33

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Acronym: SHORTCUT

Important dates

Study start
2024
Primary completion
2027
Study completion
2027
First posted
Oct 28, 2022
Registry last updated
May 29, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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