3-day IV Antibiotic Treatment Versus 3-day IV Followed by 7-day Oral Antibiotic Treatment for AP in Children

NCT05544565 | Recruiting Phase 4 DMC

• 2 other identifiers: APHP2110432021-005627-21
• Study Type: interventional
• Target: 480
• Locations: 1 country
• Sites: 15

Brief Summary

Antibiotic therapies currently recommended for the treatment of acute pyelonephritis (AP) in children, whether fully by the oral route or initially intravenous (IV, 3 days) followed by the oral route, have a duration of 7 to 14 days (10 days in France). In children with no prior urological malformation, the global clinical and microbiological cure rate after antibiotic treatment completion is around 95%. Recurrence occurs in less than 5% of cases in the 3 months following AP. Renal scarring, when documented, concerns 15% of children 6 months after treatment. Renal scarring can be associated with chronic renal disease. The investigators hypothesize that 3 days of IV treatment is equivalent to extending to 10 days with an oral to treat AP in children. The investigators also hypothesize that while achieving equivalent clinical and prevention of re-infections in the following 3 months, 3 days of IV treatment reduces the risk of acquisition of resistant strains of Enterobacteriaceae and increases the gut microbotia diversity compared to extending to 10 days with an oral therapy.

Conditions

Pyelonephritis Acute

Keywords

Pyelonephritis acute; Antibiotic therapies; Renal scar; Paediatric

Outcome Measures

Primary Outcomes (1)

• Recurrence of febrile urinary tract infection

  Demonstrate the non-inferiority of a 3-day intravenous (IV) antibiotic therapy versus a 3-day IV therapy followed by a 7-day oral antibiotic therapy for the treatment of AP in children in term of the is recurrence of febrile urinary tract infection within a 28 -days period after the completion of antibiotic treatment respectively at D31 (+/- 3 days) for the experimental group and D38 (+/- 3 days) for the control group.. The recurrence will be defined as: fever ≥ 38°C associated with a positive urinalysis (white cell counts ≥ 10\^4/mL) with a positive urine culture with one Gram-negative bacillus ≥ 10\^4 UFC/mL

  28 days (± 3 days) after the completion of antibiotic treatment.

Secondary Outcomes (4)

• Clinical cure

  D10 (+/- 3 days) for the experimental group and D17 (+/- 3 days) for the control group.

• Recurrence of AP

  90 days after the beginning of therapy

• Colonization with antimicriobial-resistant Enterobacteriaceae

  days of randomization and at D10 (+/- 3 days) for the experimental group and D17 (+/- 3 days) for the control group

• Bacterial diversity of the intestinal microbiota

  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.

Study Arms (2)

Experimental group: Discontinuation of treatment

EXPERIMENTAL

For patients randomized in the experimental group, the patient receives 3-day IV therapy and the treatment is interrupted.

Drug: IV Antibacterial Agents; Procedure: Fecal/Rectal Swab; Procedure: PCT assay

Control group: Usual practice

OTHER

For patients randomized in the control group, the treatment for acute pyelonephritis is based on the attending clinician's practice and according to the usual practice: 3-day IV therapy followed by a 7-day oral antibiotic therapy.

Drug: IV Antibacterial Agents; Drug: Orally antibacterial agents; Procedure: Fecal/Rectal Swab; Procedure: PCT assay

Interventions

IV Antibacterial Agents DRUG

Ceftriaxone (50 mg/kg once a day by intravenous/intramuscular route) AND/OR Amikacin (20 mg/kg once a day by intravenous/intramuscular route) during 3 days. .

Control group: Usual practice; Experimental group: Discontinuation of treatment

Orally antibacterial agents DRUG

Cotrimoxazole (sulfamethoxazole/trimethoprime) 30mg/kg/day (2 divided doses) OR Cefixime 8mg/kg/day (2 divided doses) during 7 days

Control group: Usual practice

Fecal/Rectal Swab PROCEDURE

Collected by the nurse or the physician (D0,D3,D10 or 17 and D31 or D38), either by a rectal swab, either by fecal swab (dip of the swab in fresh stools \< 4 hours, which will occur frequently in our population of children aged 1 month to 3 years, and will in particular be possible for hospitalized children) using a FecalSwabTM, that contains a transport medium.

Control group: Usual practice; Experimental group: Discontinuation of treatment

PCT assay PROCEDURE

Dosage of procalcitonin (if not performed in standard care) at D0

Control group: Usual practice; Experimental group: Discontinuation of treatment

Eligibility Criteria

• Age: 1 Month - 3 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age ≥ 1 month and \< 3 years
• For children younger than 3 months, gestational age \> 34 WA
• First episode of urinary tract infection
• AP defined by temperature ≥ 38°C on day of diagnosis AND positive urinalysis (white cell counts ≥ 10\^4/mL) with a positive urine culture with one Gram- negative bacillus ≥ 104 UFC/mL. The child temperature will have to be measured with a thermometer according to the French national recommendations \[Health Insurance website (AMELI ;see: - https://www.ameli. fr/assure/sante/bons-gestes/soins/prendre-temperature); HAS (see: https://www.has-sante. fr/jcms/c\_2674284/fr/prise-en-charge-de-la-fievre-chez-l-enfant)\].
• Initial treatment by either ceftriaxone AND/OR amikacin
• Outpatient or hospitalised
• Urine collected by bag
• Urine culture growing more than one dominant bacterium (cf section 6.2 of the protocol)
• Catheter-associated acute pyelonephritis
• Known congenital anomalies of the kidney and genitourinary tract (other than vesicoureteral reflux and pyelocaliceal dilatation \< 10 mm)
• Previous surgery of the genitourinary tract (except circumcision in male children)
• 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)
• Known immunocompromising condition (e.g., HIV, primary immunodeficiency, sickle cell disease, use of chronic corticosteroids or other immunosuppressive agents)
• Antibiotic prophylaxis for any reason OR antibiotic treatment in the last 7 days (except treatment administered for the AP)
• Known hypersensitivity to at least one of the active substances /excipients: ceftriaxone (including other cephalosporins and other beta-lactams) and amikacin (including other aminoglycosids).

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (15)

CH Sud Francilien

Corbeil-Essonnes, Essonne, 91100, France

NOT YET RECRUITING

Paris-Saclay hospital

Orsay, Essonne, 91400, France

RECRUITING

Antoine Beclère Hospital

Clamart, Haut de Seine, 92140, France

NOT YET RECRUITING

Ambroise Paré hospital

Boulogne, Hauts de Seine, 92100, France

RECRUITING

Children-Teenager hospital

Nantes, Loire Atlantique, 44000, France

NOT YET RECRUITING

Jeanne Flandre Hospital

Lille, Nord, 59000, France

NOT YET RECRUITING

Robert Debré Hospital

Paris, Paris, 75019, France

NOT YET RECRUITING

Robert Debré Hospital

Paris, Paris, 75019, France

NOT YET RECRUITING

Meaux Hospital

Meaux, Seine et Marne, 77100, France

NOT YET RECRUITING

Jean Verdier Hospital

Bondy, Seine St Denis, 93140, France

NOT YET RECRUITING

Intercomunal Créteil Hospital

Créteil, Val de Marne, 94000, France

NOT YET RECRUITING

Kremlin Bicêtre Hospital

Le Kremlin-Bicêtre, Val de Marne, 94270, France

NOT YET RECRUITING

Andre mignot hospital

Le Chesnay, Yvelines, 78150, France

RECRUITING

GHEF Site Marne la vallée

Jossigny, France

NOT YET RECRUITING

CHU Toulouse

Toulouse, France

NOT YET RECRUITING

MeSH Terms

Interventions

Anti-Bacterial Agents; Defecation

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Digestive System Physiological Phenomena; Digestive System and Oral Physiological Phenomena

Study Officials

• Jean GASCHIGNARD, PhD

  Hôpital Paris-Saclay

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jean GASCHIGNARD, PhD

CONTACT

+33 1 69 15 96 00; j.gaschignard@ghne.fr

Romain BASMACI, PhD

CONTACT

+33 1 47 60 63 58; romain.basmaci@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open, multicentric, parallel group non-inferiority clinical trial with 1:1 randomization

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: September 16, 2022
• Study Start: March 22, 2023
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: January 7, 2026

Record last verified: 2025-09

Locations

FR (15)