3-day intravenous antibiotic treatment versus 3-day intravenous followed by 7-day oral antibiotic treatment for acute pyelonephritis in children 1 month to 3 years old: a non-inferiority open randomized multicentric clinical trial PYELOCOURT

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Decision date (initial)

2024-11-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

French Ministry of Health (DGOS)

External identifiers

EU CT number

2024-518930-10-00

EudraCT number

2021-005627-21

ClinicalTrials.gov

NCT05544565

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The main objective is to demonstrate the non-inferiority of treating AP in
children by a 3-day intravenous (IV) antibiotic therapy versus a 3-day IV
therapy followed by a 7-day oral antibiotic therapy, comparing the rate of
recurrence of febrile urinary tract infection within the 28-day period after
the completion of antibiotic treatment.

Secondary objectives 2

1. To demonstrate the non-inferiority of a 3-day IVantibiotic treatment versus a 3-day IV followed by 7-day oral antibiotic treatment for AP in children 1 month to 3 years old in terms of: 1. Clinical cure at day 14 2. Recurrence of AP within the 90 days after the beginning of therapy.
2. - To compare between the two treatment arms: 3. The rate of colonization with antimicrobial-resistant Enterobacteriaceae 4. The bacterial diversity of the intestinal microbiota.

Conditions and MedDRA coding

acute pyelonephritis (AP) in children

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. - Age ≥ 1 month and < 3 years o For children younger than 3 months, gestational age > 34 WA
2. First episode of urinary tract infection
3. AP defined by temperature ≥ 38°C on day of diagnosis AND positive urinalysis (white cell counts ≥ 104/mL).The child temperature will have to be measured with a thermometer according to the French national recommendations [Health Insurance website (AMELI ;see: - https://www.ameli. fr/assure/sante/bons-gestes/soins/prendretemperature); HAS (see: https://www.has-sante. fr/jcms/c_2674284/fr/prise-en-charge-de-la-fievre-chez-l-enfant)].
4. Initial treatment by either ceftriaxone AND/OR amikacin
5. - Outpatient or hospitalised

Exclusion criteria 16

1. - Urine collected by bag
2. - Urine culture growing more than one dominant bacterium (cf section 6.2 of the protocol) Catheter-associated acute pyelonephritis
3. - Known congenital anomalies of the kidney and genitourinary tract (other than vesicoureteral reflux and pyelocaliceal dilatation < 10 mm)
4. - Previous surgery of the genitourinary tract (except circumcision in male children)
5. - Abnormal renal function for age and weight (defined by a serum creatinine >40µmol/L before 1 year and >75µmol between 1 year et 3 years)
6. - Known immunocompromising condition (e.g., HIV, primary immunodeficiency, sickle cell disease, use of chronic corticosteroids or other immunosuppressive agents)
7. - Antibiotic prophylaxis for any reason OR antibiotic treatment in the last 7 days (except treatment administered for the AP)
8. - Known hypersensitivity to at least one of the active substances /excipients: ceftriaxone (including cephalosporin and beta-lactams) and amikacin (including aminoside)
9. - Known hypersensitivity to at least one of the active substances /excipients: cotrimoxazole (=sulfamethoxazole/trimethoprim) (including sulfonamide) and cefixime (including cephalosporin)
10. - Known hypersensitivity to 99mTc-DMSA (medicinal product used for renal scintigraphy)
11. - Known severe hepatic insufficiency
12. - Known complete G6PD deficiency
13. - No written consent from holders of parental authority
14. - Non-affiliation to a social security system (as beneficiary or entitled person)
15. - Children whose follow-up is not carried out in the centre
16. - Participation in another interventional or minimal risk trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint isrecurrence of febrile urinary tract infection within a 28 days period after the end completion of antibiotic treatment respectively at D31 (+/- 3 days) for the experimental group and D38 (+/- 3 days) for the control group.

Secondary endpoints 4

1. Clinical cure 7 days after end of treatment, defined by apyrexia AND absence of signs suggestive of urinary infection (abdominal pain, urinary function signs) AND no feeding problem collected during a medical visit, respectively at D10 (+/- 3 days) for the experimental group and D17 (+/- 3 days) for the control group.
2. Recurrent of AP within 90 days after the beginning of therapy (day 90 ± 15 days) collected during a phone call.
3. Colonization with antimicrobial resistant Enterobacteriaceae in the gastrointestinal tract at days of randomization and at D10 (+/- 3 days) for the experimental group and D17 (+/- 3 days) for the control group
4. Alpha-diversity measured by Shannon’s index at inclusion, randomization, and at D10 (+/- 3 days) and D31 (+/- 3 days) for the experimental group, and D17 (+/- 3 days) and D38 (+/- 3 days) for the control group .

Investigational products

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

Test 4

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 Jean GASCHIGNARD

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Jean GASCHIGNARD

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

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

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