Short Therapy for Febrile UTI in Childhood

Shortened Antibiotic Therapy for Febrile Urinary Tract Infection (UTI) in Childhood: a Multicenter Randomized Controlled Trial

Febrile urinary tract infections (UTIs) are common in children, but there is no consensus concerning the duration of the antibiotic treatment. Current recommendations include the use of an oral antibiotic, chosen between amoxicillin and clavulanic acid or a third-generation cephalosporin (ceftibuten), for a minimum of seven to a maximum of 14 days. In an antibiotic overuse-sparing model, proper evaluation of a shorter therapy in the treatment of febrile UTI in childhood is lacking.

The objective of this randomized controlled trial is to assess the non inferiority of a five days oral course of amoxicillin and clavulanic acid vs the standard 10-day regimen in the treatment of febrile UTIs in children.

The trial results might provide evidence of the non-inferiority of a short duration of the antibiotic course for the treatment of febrile UTI in childhood, contributing to a reduction in the over-use of antibiotics and consequently limiting the emergence of antibiotic resistance.

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infections
• Intervention / Treatment: Drug: Amoxicillin and Clavulanic Acid in Oral Dose Form

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Emilia Romagna
    • Bologna, Emilia Romagna, Italy, 40138
      • Policlinico S.Orsola-Malpighi
    • Ravenna, Emilia Romagna, Italy, 48121
      • Santa Maria delle Croci Hospital
  • Friuli Venezia Giulia
    • Monfalcone, Friuli Venezia Giulia, Italy, 34074
      • Ospedale San Polo
    • Pordenone, Friuli Venezia Giulia, Italy, 33170
      • Pediatric Department, Santa Maria degli Angeli Hospital
    • Trieste, Friuli Venezia Giulia, Italy, 34137
      • Institute for Maternal and Child Health IRCCS Burlo Garofolo
    • Udine, Friuli Venezia Giulia, Italy, 33100
      • ASUIUD Azienda sanitaria universitaria integrata di Udine
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Fondazione Policlinico Agostino Gemelli - IRCCS City Rome
  • Lombardia
    • Milano, Lombardia, Italy, 20122
      • Fondazione IRCSS Ca Granda, Policlinico di Milano
  • Marche
    • Ancona, Marche, Italy, 60123
      • Ospedali Riuniti di Ancona - Ospedale Salesi
  • Sicilia
    • Messina, Sicilia, Italy, 98124
      • A.O.U.G. Martino
  • Veneto
    • Belluno, Veneto, Italy, 32100
      • San Martino Hospital
    • Padua, Veneto, Italy, 35128
      • Department of Woman and Child Health, University of Padua City
    • Treviso, Veneto, Italy, 31100
      • UOC Pediatria Ospedale Ca' Foncello

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age from 3 months to 5 years;
2. Clinical diagnosis of febrile UTI, defined by fever ≥38°C and positive result of urinalysis (nitrite and/or leukocyte esterase positivity) in two consecutive urine samples collected by bladder catheterization or clean catch (19). The diagnosis of UTI will be then confirmed by positive urine culture for a single type of bacterium with a charge> 105 CFU /ml as per the Recommendations of the Italian Society of Pediatric Nephrology (SINePe) (19).

Exclusion Criteria:

1. "Complicated" febrile UTI (septic appearance, repeated vomiting impeding oral administration of the antibiotic, severe-moderate dehydration with the need for intravenous antibiotic therapy)
2. Presence of an inserted urinary catheter
3. Immunodeficiency
4. Hypersensitivity to the active substance or other beta-lactam antibiotics
5. Any antibiotic treatment received in the previous 15 days.
6. Presence of another poorly controlled chronic medical condition (diabetes, inflammatory bowel disease, etc.)
7. Presence of neurological bladder
8. Presence of phenylketonuria or glucose-galactose malabsorption
9. Intestinal malabsorption
10. Poor compliance
11. History of jaundice or liver failure positive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Short treatment group; Amoxicillin and clavulanic acid 50 mg/kg three times daily administered orally for 5 consecutive days	Drug: Amoxicillin and Clavulanic Acid in Oral Dose Form; 50 mg/kg three times daily administered orally
Active Comparator: Standard treatment group; amoxicillin and clavulanic acid 50 mg/kg three times daily administered orally for 10 consecutive days	Drug: Amoxicillin and Clavulanic Acid in Oral Dose Form; 50 mg/kg three times daily administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of infection recurrence	Infection recurrence rate is defined as the reappearance of signs and symptoms of febrile UTI by the first day after the end of antibiotic therapy	within 30 days after the end of the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of complete resolution of signs and symptoms	The complete resolution of the signs and symptoms (clinical assessment and urinalysis) related to the infection evaluated at the end of the treatment, without the need for additional or alternative antibiotic therapy (short term clinical efficacy)	within 30 days after the end of the intervention
Rate of antibiotic-resistant or of opportunistic strains in relapses	Antibiotic resistance is defined as the presence of positive urinalysis and positive urine culture for a single type of bacterium resistant to amoxicillin and clavulanic acid, after treatment in case of relapse. The bacterial growth will be considered significant if >105 colony-forming unit/ml (CFU/ml) (>104 CFU/ml for urine samples collected by bladder catheterization). Urine cultures containing more than one bacterial species will be considered contaminated.	within 30 days after the end of the intervention

Collaborators and Investigators

• Sponsor: IRCCS Burlo Garofolo
• Investigators: Study Chair: Egidio Barbi, MD Prof, Institute for maternal and child health Burlo Garofolo; Principal Investigator: Marco Pennesi, MD, Institute for maternal and child health Burlo Garofolo

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2020
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: May 19, 2020
• First Submitted That Met QC Criteria: May 19, 2020
• First Posted (Actual): May 22, 2020

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 28, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: children; urinary tract infection; short antibiotic therapy
• Additional Relevant MeSH Terms: Urologic Diseases; Infections; Urinary Tract Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Amoxicillin; Clavulanic Acid; Clavulanic Acids
• Other Study ID Numbers: RC 10/18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No