Efficacy of 7 days versus 14 days of antibiotic therapy for acute pyelonephritis in kidney transplant recipients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01], Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

25 Mar 2024 → ongoing

Decision date (initial)

2024-06-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ministery of Health

External identifiers

EU CT number

2024-513328-40-00

EudraCT number

2022-002319-43

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To show that a 7 day-antibiotic therapy is not inferior to a 14 day-antibiotic therapy in the treatment of acute pyelonephritis in kidney transplant recipients.

Secondary objectives 11

1. To compare between both arms:
2. Clinical cure at day 90 and day 180
3. Microbiological cure at day 30, 90 and 180
4. Tolerance and safety of antibiotics
5. Hospitalization length stay
6. Antibiotic consumption during total follow up
7. Acquisition of antibiotic resistant Enterobacteriaceae
8. Kidney graft function and transplant rejection at day 90 and day 180
9. The total costs.
10. To evaluate risk factors for failure and relapse/recurrence.
11. To evaluate efficacy of the antibiotic treatment at the end of treatment (D7 for experimental arm and D14 for control group)

Conditions and MedDRA coding

Pyelonephritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age >18 years Kidney Transplant Recipients
2. APN defined by: fever (T°≥38°C) (with or without clinical signs and/or symptoms of UTI) and pyuria (≥104 white blood cells/mL or ≥10/mm3) and positive urine culture (uropathogen ≥103 CFU/mL susceptible to the empirically administrated antibiotic)
3. No confirmed or suspected febrile non urinary bacterial infection
4. No urologic/renal complication at baseline imaging (abscess, obstruction...)
5. 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.
6. Written informed consent

Exclusion criteria 21

1. Patients with any of the following conditions
2. Severe or complicated condition
3. 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
4. Admission or stay in intensive care unit at baseline
5. Obstruction of the urinary tract
6. Renal, perinephric or prostatic abscess
7. prior inclusion in this study
8. current participation to another interventional study
9. Dual antibiotic therapy ((prophylactic antibiotic such as cotrimoxazole allowed) )(only 1 dose of aminoside is allowed before randomization)
10. First month post transplantation
11. -Current indwelling catheter (including bladder catheter, ureteral stents, percutaneous nephrostomy tubes)
12. Neurogenic bladder
13. Enterocystoplasty
14. Immunodeficiency or immunosuppressive therapy not related to kidney transplantation, including hematologic malignancy, cancer, asplenia, neutropenia<500 neutrophils/mm3,
15. Pregnancy, breastfeeding
16. Hypersensitivity or previous severe adverse drug reaction to the antibiotic therapy
17. Unable or unwilling, in the judgment of the investigator, to comply with the protocol
18. Life expectancy<1 month
19. Patient under legal guardianship or without healthcare coverage
20. Homeless patient
21. Women with childbearing potential not using adequate contraception

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 UTI.

Secondary endpoints 8

1. Clinical cure at day 90 and 180
2. Microbiological cure *at day 30, 90 and 180
3. Incidence of relapse /recurrence between day 30 and day 90
4. Incidence of adverse events imputable to antibiotic treatment
5. Kidney function assessed according to MDRD (Modification of Diet in Renal Disease) or CKD (Chronic Kidney Disease - Epidemiology Collaboration) epi
6. Hospitalization length stay defined by the delay between the date of inclusion and the date of hospital discharge
7. Antibiotic consumption
8. Rectal carriage of antibiotic resistant Enterobacteriaceae at inclusion and day 30

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr. Matthieu LAFAURIE

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr. Matthieu LAFAURIE

Locations

1 EU/EEA country · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications