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INterest of the Negative Predictive Value of Integrons in Choosing a Narrow-spectrum Empirical anTibiotic Treatment vs Usual Empirical Antibiotic Treatment for Urinary Tract infectionS in the PEDiatric Emergency Department (INVICTUS PED)

Primary Purpose

Urinary Tract Infections in Children

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
integron research
usual practice
Sponsored by
University Hospital, Limoges
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Urinary Tract Infections in Children focused on measuring empirical antibiotic treatment, biomarker, urinary tract infection, antibiotic resistance, pediatric emergency department

Eligibility Criteria

3 Months - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Children above 3 months old and under 18 years old
  • Consultation in a participating pediatric emergency department
  • Suspicion of UTI with fever (Fever ≥ 38°C and urine dipstick test positive for leukocytes and/or nitrites)
  • First episode of UTI with fever
  • Written informed consent of the holders of parental authority
  • Affiliated to Social Security

Exclusion Criteria:

  • Criteria of severity:

    • Severe infection with severe sepsis or septic shock
    • Dehydration ≥ 10%
    • Fever ≥ 38°C > 4 days (96h)
    • Indication of surgical or interventional drainage
  • Complication risk factors:

    • Any anatomic or functional defect of the urinary tract
    • Pregnancy
    • Severely immunocompromised patient
    • Severe chronic renal failure defined as a clearance < 30 mL/min/1.73 m2
    • Severe liver failure
  • 3GC allergy
  • Contra-indication to SXT:

    • G6PD deficiency
    • Treatment with methotrexate
    • Allergy to sulfonamide
  • Antibiotic treatment within 48h before admission
  • Empirical antibiotic treatment not recommended

Sites / Locations

  • Bordeaux university HospitalRecruiting
  • Limoges university HospitalRecruiting
  • Montpellier university HospitalRecruiting
  • Toulouse university HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Integron research

Usual practice

Arm Description

Empirical antibiotic treatment chosen based on the results of the integron search: when PCR is negative, patients will receive SXT (30 mg/kg/j of sulfamethoxazole and 6 mg/kg/j of trimethoprim) when PCR is positive or uninterpretable for integrons, patients will receive an empirical antibiotic treatment based on the usual practice of each center according to the GPIP guidelines.

Empirical antibiotic treatment based on the usual practice of each center according to the GPIG guidelines.

Outcomes

Primary Outcome Measures

Recovery
Recovery defined as, apyrexia obtained within less than 72h and no persistence or repetition of UTI with fever and no change of empirical antibiotic therapy required because of resistance and no treatment interruption for adverse effects

Secondary Outcome Measures

patients treated
Number of patients treated with 3GC in both groups, during the participation of each patient
Duration treatment
Duration of treatment with 3GC in both groups for patient treated, during the participation of each patient
Antibiotic treatment changes
In both groups, description of antibiotic treatment changes based on the AST results, according to 4 criteria: Change because of resistance Narrowing of the antibiotic spectrum Interruption because the diagnosis of UTI was ruled out Antibiotics used
Adaptation of antibiotherapy with the AST result
Proportion of patients in both groups for whom empirical antibiotic treatment was adapted to the AST results and did not require any change (because of resistance, or to narrow the antibiotic spectrum)
Resistance of enterobacteria
In the study population, percentage of resistance of enterobacteria to the different antibiotic classes
Predictive values of the integrons
Negative and positive predictive values of the integrons depending on the main antibiotic classes used in the experimental group.
Apyrexia
Time to apyrexia from the start of the antibiotic therapy compared between both groups.
Early repetition of urinary tract infection
Proportion of early repetition of urinary tract infection with fever in both groups.
Treatment interruption for adverse effects
Proportion of treatment interruption for adverse effects in both groups.
Time spent in the pediatric emergency department
Time spent in the pediatric emergency department in both groups

Full Information

First Posted
September 16, 2021
Last Updated
September 13, 2023
Sponsor
University Hospital, Limoges
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1. Study Identification

Unique Protocol Identification Number
NCT05066854
Brief Title
INterest of the Negative Predictive Value of Integrons in Choosing a Narrow-spectrum Empirical anTibiotic Treatment vs Usual Empirical Antibiotic Treatment for Urinary Tract infectionS in the PEDiatric Emergency Department
Acronym
INVICTUS PED
Official Title
INterest of the Negative Predictive Value of Integrons in Choosing a Narrow-spectrum Empirical anTibiotic Treatment vs Usual Empirical Antibiotic Treatment for Urinary Tract infectionS in the PEDiatric Emergency Department
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 18, 2022 (Actual)
Primary Completion Date
November 18, 2025 (Anticipated)
Study Completion Date
November 18, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Limoges

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
INVICTUS PED primary objective is to show the non-inferiority of an empirical antibiotic therapeutic management guided by the early detection of integrons in the urine, compared to a usual empirical antibiotic treatment, for the recovery of children admitted to the pediatric emergency department (ED) with a non-severe urinary tract infection (UTI) with fever
Detailed Description
Urinary tract infections with fever are common in children and require primary health care management. Because of the risk of immediate evolution to a systemic infection with long-term renal scars, empirical antibiotic treatment is recommended. The French Group for Pediatric Infectious Diseases (GPIP) recommends the use of third-generation cephalosporins (3GC) targeting enterobacteria, which are mainly involved in UTI and increasingly resistant to antibiotics through the production of extended-spectrum β-lactamases. However, use of 3GC is a well-known risk factor for resistant germs selection and one of the main guideline to fight antibiotic resistance, which is an important public health issue, is to reduce their use. Integrons are genetic elements involved in the spread of antibiotic resistance in enterobacteria. Preliminary studies showed that integron search using polymerase chain reaction (PCR) directly on urine samples had a great NPV (>98%) for trimethoprim-sulfamethoxazole (SXT). The hypothesis is that, in children presenting to the pediatric ED with non-severe UTI with fever, absence of integron in their urine could allow prescribing an empirical antibiotic treatment with SXT without decreasing the chance of recovery, thus decreasing the use of 3GC. Two strategies is compare: i) In the control group: empirical antibiotic treatment according to the usual practice of each center, in line with the GPIP guidelines, ii) in the experimental group: empirical antibiotic treatment chosen depending on the results of the integron search with PCR. When PCR is positive, treatment according to usual practice; when PCR is negative, treatment with SXT. Two follow-up visits, by phone, will be planned: at H48 (+ 24h), when the empirical antibiotic treatment is assessed based on the urine culture and antimicrobial susceptibility test (AST) results, and on D30 (+/- 2 days) at the end of the follow-up.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urinary Tract Infections in Children
Keywords
empirical antibiotic treatment, biomarker, urinary tract infection, antibiotic resistance, pediatric emergency department

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
232 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Integron research
Arm Type
Experimental
Arm Description
Empirical antibiotic treatment chosen based on the results of the integron search: when PCR is negative, patients will receive SXT (30 mg/kg/j of sulfamethoxazole and 6 mg/kg/j of trimethoprim) when PCR is positive or uninterpretable for integrons, patients will receive an empirical antibiotic treatment based on the usual practice of each center according to the GPIP guidelines.
Arm Title
Usual practice
Arm Type
Other
Arm Description
Empirical antibiotic treatment based on the usual practice of each center according to the GPIG guidelines.
Intervention Type
Procedure
Intervention Name(s)
integron research
Intervention Description
Patients with suspected UTI with fever will be screened at their admission to the pediatric ED. Urine samples will be sent to the laboratory for culture and integron PCR according to routine practice. Results of the integron search will be given to the investigator. Patients in the experimental group with a positive or uninterpretable PCR will also receive an empirical antibiotic treatment based on the usual practice of each center according to the GPIP guidelines. Patients in the experimental group with a negative PCR will receive a treatment with SXT at the recommended dose.
Intervention Type
Procedure
Intervention Name(s)
usual practice
Intervention Description
Patients with suspected UTI with fever will be screened at their admission to the pediatric ED. Patients in the control group will receive an empirical antibiotic treatment based on the usual practice of each center according to the GPIP guidelines.
Primary Outcome Measure Information:
Title
Recovery
Description
Recovery defined as, apyrexia obtained within less than 72h and no persistence or repetition of UTI with fever and no change of empirical antibiotic therapy required because of resistance and no treatment interruption for adverse effects
Time Frame
Day 30
Secondary Outcome Measure Information:
Title
patients treated
Description
Number of patients treated with 3GC in both groups, during the participation of each patient
Time Frame
Day 30
Title
Duration treatment
Description
Duration of treatment with 3GC in both groups for patient treated, during the participation of each patient
Time Frame
Day 30
Title
Antibiotic treatment changes
Description
In both groups, description of antibiotic treatment changes based on the AST results, according to 4 criteria: Change because of resistance Narrowing of the antibiotic spectrum Interruption because the diagnosis of UTI was ruled out Antibiotics used
Time Frame
Hour 48
Title
Adaptation of antibiotherapy with the AST result
Description
Proportion of patients in both groups for whom empirical antibiotic treatment was adapted to the AST results and did not require any change (because of resistance, or to narrow the antibiotic spectrum)
Time Frame
Hour 48
Title
Resistance of enterobacteria
Description
In the study population, percentage of resistance of enterobacteria to the different antibiotic classes
Time Frame
Hour 48
Title
Predictive values of the integrons
Description
Negative and positive predictive values of the integrons depending on the main antibiotic classes used in the experimental group.
Time Frame
Hour 48
Title
Apyrexia
Description
Time to apyrexia from the start of the antibiotic therapy compared between both groups.
Time Frame
Hour 48
Title
Early repetition of urinary tract infection
Description
Proportion of early repetition of urinary tract infection with fever in both groups.
Time Frame
Day 30
Title
Treatment interruption for adverse effects
Description
Proportion of treatment interruption for adverse effects in both groups.
Time Frame
Day 30
Title
Time spent in the pediatric emergency department
Description
Time spent in the pediatric emergency department in both groups
Time Frame
Day 30

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Children above 3 months old and under 18 years old Consultation in a participating pediatric emergency department Suspicion of UTI with fever (Fever ≥ 38°C and urine dipstick test positive for leukocytes and/or nitrites) First episode of UTI with fever Written informed consent of the holders of parental authority Affiliated to Social Security Exclusion Criteria: Criteria of severity: Severe infection with severe sepsis or septic shock Dehydration ≥ 10% Fever ≥ 38°C > 4 days (96h) Indication of surgical or interventional drainage Complication risk factors: Any anatomic or functional defect of the urinary tract (other than low-grade VUR and calyceal dilation < 10 mm) Repetition of UTI with fever ≤ than 6 months since the previous episode Repetition of UTI with fever and anatomic or functional defect of the urinary tract Pregnancy Severely immunocompromised patient Severe chronic renal failure defined as a clearance < 30 mL/min/1.73 m2 Severe liver failure 3GC allergy Contra-indication to SXT: G6PD deficiency Treatment with methotrexate Allergy to sulfonamide Antibiotic treatment within 48h before admission Empirical antibiotic treatment not recommended
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christine LAGUILLE, MD
Phone
0555058664
Ext
+33
Email
christine.laguille@chu-limoges.fr
Facility Information:
Facility Name
Bordeaux university Hospital
City
Bordeaux
ZIP/Postal Code
33000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marion FAVIER, MD
First Name & Middle Initial & Last Name & Degree
Marion FAVIER, MD
Facility Name
Limoges university Hospital
City
Limoges
ZIP/Postal Code
87042
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christine LAGUILLE, MD
Phone
0555058664
Ext
+33
Email
christine.laguille@chu-limoges.fr
First Name & Middle Initial & Last Name & Degree
Christine LAGUILLE, MD
Facility Name
Montpellier university Hospital
City
Montpellier
ZIP/Postal Code
34000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brigitte BLANC, MD
First Name & Middle Initial & Last Name & Degree
Brigitte BLANC, MD
Facility Name
Toulouse university Hospital
City
Toulouse
ZIP/Postal Code
31000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Camille BREHIN, MD
First Name & Middle Initial & Last Name & Degree
Camille BREHIN, MD

12. IPD Sharing Statement

Learn more about this trial

INterest of the Negative Predictive Value of Integrons in Choosing a Narrow-spectrum Empirical anTibiotic Treatment vs Usual Empirical Antibiotic Treatment for Urinary Tract infectionS in the PEDiatric Emergency Department

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