Pyelonephritis AcutePhase 3SHORTCUTNCT05597540
Efficacy of 7 Days Versus 14 Days of Antibiotic Therapy for Acute Pyelonephritis in Kidney Transplant Recipients, a Multicentre Randomized Non-inferiority Trial.
A Phase 3 study testing Short antibiotic treatment and Usual antibiotic treatment in people with Pyelonephritis Acute and Kidney Transplant Infection, run by Assistance Publique - Hôpitaux de Paris at 9 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pyelonephritis Acute, Kidney Transplant Infection
- What is being tested?
- Short antibiotic treatment and Usual antibiotic treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 470 participants
- Where
- 9 sitesFrance
- Study dates
- 22 Feb 2024to 22 Aug 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
France9 sites, 9 recruiting
- Not yet recruiting
CHU Bordeaux
Bordeaux
Hannah Kaminski, Dr
- Not yet recruiting
Hôpital Foch
Boulogne-Billancourt
Michel Delahousse, Dr
- Recruiting
CHU Mondor
Créteil
Marie Matignon, Dr
- Not yet recruiting
CHU Lyon
Lyon
Charlene Levi, Dr
- Recruiting
CHU Nantes
Nantes
Clément Deltombe, Dr
- Not yet recruiting
CHU Kremlin-Bicêtre
Paris
Renaud Snanoudj, Pr
- Recruiting
CHU Necker
Paris
Carole Burger, Dr
- Recruiting
CHU Saint Louis
Paris
Gillian Divard, Dr
- Not yet recruiting
CHU Toulouse
Toulouse
Nassim Kamar, Pr
About this study
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
- Being tested
- Short antibiotic treatment, Usual antibiotic treatment
- Keywords
- antibiotic therapy, duration of antibiotic treatment reduction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Short antibiotic treatmentDrug
7 day-duration antibiotic treatment. The choice of antibiotic treatment is left to the medical team in charge of the patient.
Usual antibiotic treatmentDrug
14 day-duration antibiotic treatment. The choice of antibiotic treatment is left to the medical team in charge of the patient.
| Study group | Role | What they receive |
|---|---|---|
| 7 day-duration antibiotic treatment | Experimental | Not described Receives: Drug: Short antibiotic treatment |
| 14 day-duration antibiotic treatment | Active comparator | Not described Receives: Drug: Usual antibiotic treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: at day 30
Secondary outcomes (14)
Clinical cure 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).
Measured: at day 90
Clinical cure 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).
Measured: at day 180
Microbiological cure day 30
Microbiological cure is defined as a sterile urine or uropathogene ≤ 10.3 CFU/mL in urine culture
Measured: at day 30
Microbiological cure day 90
Microbiological cure is defined as a sterile urine or uropathogene ≤ 10.3 CFU/mL in urine culture
Measured: at day 90
Microbiological cure day 180
Microbiological cure is defined as a sterile urine or uropathogene ≤ 10.3 CFU/mL in urine culture
Measured: at day 180
Incidence of relapse/recurrence day 30
Relapse or recurrence of the Urinary Tract Infection
Measured: at day 30
Incidence of relapse/recurrence day 90
Relapse or recurrence of the Urinary Tract Infection
Measured: at day 90
Incidence of adverse event
Incidence of adverse events imputable to antibiotic treatment
Measured: at day 180
Kidney function
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
Measured: at day 90
Kidney function
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
Measured: at day 180
Hospital length of stay
Hospitalisation length stay defined by the delay between the date of inclusion and the date of hospital discharge
Measured: Up to day 180
Antibiotic consumption
Antibiotic consumption (indication, dose and duration) throughout the follow-up will be recorded.
Measured: Up to day 180
Rectal carriage
Rectal carriage of antibiotic resistant Enterobacteriaceae
Measured: at inclusion
Rectal carriage
Rectal carriage of antibiotic resistant Enterobacteriaceae
Measured: at day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2022
- Study start22 Feb 2024
- Primary completion22 Mar 2027 (estimated)
- Study completion22 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pyelonephritis AcuteStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 470 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05597540
- Sponsor's protocol ID
- APHP200020
- Acronym
- SHORTCUT
- Status last verified
- Feb 2024
- First submitted
- 24 Oct 2022
- Last updated
- 29 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT05597540
- Acronym / sponsor ID
- SHORTCUT / APHP200020
- Conditions
- Pyelonephritis Acute, Kidney Transplant Infection
- Keywords
- antibiotic therapy, duration of antibiotic treatment reduction
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 470 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 22 Feb 2024 (actual)
- Primary completion
- 22 Mar 2027 (estimated)
- Study completion
- 22 Aug 2027 (estimated)
- First posted
- 28 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 7 day-duration antibiotic treatment | Experimental | Drug: Short antibiotic treatment |
| 14 day-duration antibiotic treatment | Active comparator | Drug: Usual antibiotic treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (20 listed)
- Severe or complicated condition
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Short antibiotic treatment7 day-duration antibiotic treatment. The choice of antibiotic treatment is left to the medical team in charge of the patient. | Drug | 7 day-duration antibiotic treatment |
| Usual antibiotic treatment14 day-duration antibiotic treatment. The choice of antibiotic treatment is left to the medical team in charge of the patient. | Drug | 14 day-duration antibiotic treatment |
Primary outcome
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).
14 secondary outcomes
Clinical cure day 90
Time frame: at day 90
Clinical cure day 180
Time frame: at day 180
Microbiological cure day 30
Time frame: at day 30
Microbiological cure day 90
Time frame: at day 90
Microbiological cure day 180
Time frame: at day 180
Incidence of relapse/recurrence day 30
Time frame: at day 30
Incidence of relapse/recurrence day 90
Time frame: at day 90
Incidence of adverse event
Time frame: at day 180
Kidney function
Time frame: at day 90
Kidney function
Time frame: at day 180
Hospital length of stay
Time frame: Up to day 180
Antibiotic consumption
Time frame: Up to day 180
Rectal carriage
Time frame: at inclusion
Rectal carriage
Time frame: at day 30
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Short antibiotic treatment and Usual antibiotic treatment in people with Pyelonephritis Acute and Kidney Transplant Infection, run by Assistance Publique - Hôpitaux de Paris at 9 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Matthieu Lafaurie, MD (142494117 ext. +33, matthieu.lafaurie@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical cure day 30 (time frame: at day 30). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2024.