Efficacy and safety of circumcision alone on risk of febrile urinary tract infections in boys with posterior urethral valves: a prospective randomized open-label multicentric trial enriched with historic controls

2024-519166-48-01 Protocol CHUBX 2023/52 Therapeutic exploratory (Phase II) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 13 sites · Protocol CHUBX 2023/52

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Authorised, recruitment pending
Participants planned 163
Countries 1
Sites 13

Posterior Urethral Valves

To assess the effect of circumcision alone on risk of fUTIs at 2-years, in children with PUV, as well as the effect of the combination of circumcision and antibiotic prophylaxis; and of antibiotic prophylaxis alone by enrichment with historic controls.

Key facts

Sponsor
Centre Hospitalier Universitaire De Bordeaux
Participant type
Pediatric, Patients
Age range
0-17 years
Gender
Male
Therapeutic area
Diseases [C] - Male Urogenital Diseases [C12]
Decision date (initial)
2025-06-06
Transition trial
No
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
Yes
Funding sources
Ministère de la Santé AAP DGOS PHRC-N 2022 (PHRC-22-0045)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess the effect of circumcision alone on risk of fUTIs at 2-years, in children with PUV, as well as the effect of the combination of circumcision and antibiotic prophylaxis; and of antibiotic prophylaxis alone by enrichment with historic controls.

Secondary objectives 7

  1. To assess the median number of fUTIs at 2 years in children with at least 1 fUTI during follow-up
  2. To assess the proportion of children with worsening renal scans on DMSA scan between baseline and 2-years between children with and without fUTIs
  3. To describe the bacteria responsible for the fUTIs
  4. To explore potential risk factors for presenting fUTIs
  5. To explore the effects of the strategies under evaluation in participants with and without urinary reflux at baseline
  6. To describe adherence to antibiotic prophylaxis in control group
  7. To explore comparatively the differences in risk of fUTI according to preventive strategy (circumcision alone, circumcision and antibiotic prophylaxis, antibiotic prophylaxis alone)

Conditions and MedDRA coding

Posterior Urethral Valves

Study design 2 periods

#TitleAllocationBlindingRoles blindedArms
1 Prospective strategies
Prospective research procedures in CIRCUP2: Randomization at baseline (J0) Follow-up visits at M1, M3, M6, M12, M18 and M24 DMSA scan at M1 and M24.
 Randomised Controlled None Research Strategy: Prospective strategy administered to participants of CIRCUP 2: Antibiotics-sparing strategy: Circumcision alone, performed at the time of valve resection
Reference/comparative strategy: Circumcision, performed at the time of valve resection, plus daily antibiotic prophylaxis up to two years
2 Retrospective researches in CIRCUP2
Use of data from historical controls from CIRCUP trial
 Not Applicable None Use of data from CIRCUP Circumcision + antibiotic prophylaxis group: Use of data from patients of CIRCUP with Circumcision plus daily antibiotic prophylaxis up to two years
Use of data from CIRCUP antibiotic prophylaxis group: Use od data from patients of CIRCUP with daily antibiotic prophylaxis up to two years

Regulatory references

Plan to share IPD
No
EU CT numberTitleSponsor
2024-519166-48-00 Efficacy and safety of circumcision alone on risk of febrile urinary tract infections in boys with posterior urethral valves: a prospective randomized open-label multicentric trial enriched with historic controls. CIRCUP 2 Centre Hospitalier Universitaire De Bordeaux

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

  1. For prospective groups: Male child aged 1 to 31 days
  2. For prospective groups: Valve resection and circumcision performed before 1 month of life.
  3. For prospective groups: Adult guardians (>18 years)
  4. For prospective groups: Posterior urethral valves diagnosed by cystography within the first 28 days of life
  5. For prospective groups: Parental guardians affiliated with a social security system
  6. For prospective groups: Parental guardians who have signed an informed consent allowing their child to participate in the study
  7. For retrospective groups from CIRCUP : Parental guardians who are not opposed to their child's participation in the trial
  8. For prospective groups: Parental guardians giving consent must be able to understand the trial in its entirety

Exclusion criteria 4

  1. Long-term antibiotics use indicated for other reasons than PUV
  2. Mental state rendering the person giving consent incapable of understanding the trial
  3. Parents being a relative of the investigator or a relative of someone from the team directly involved in the trial, including assistant doctors, pharmacists, nurses, and trial coordinators
  4. Known contra-indication to all antibiotics used in the study (Alfatil®, Bactrim®, Augmentin®)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Time to first fUTI between baseline and 2 years. The diagnosis of fUTI is defined as fever (>38.5° Celsius) with evidence of pyuria and culture-proven infection on urinalysis, obtained by urethral catheterization or suprapubic aspiration, as well as biological signs of inflammation.

Secondary endpoints 7

  1. Median number of fUTIs at 2 years in children with at least 1 fUTI during follow-up
  2. The proportion of children with worsening renal scans (defined as an increase in heterogeneity and number of cortical defects) between baseline and 2-years between children with and without fUTIs
  3. The types of germs responsible for fUTIs
  4. Baseline risk factors for fUTIs from regression models (exploratory)
  5. Exploratory sub-group analyses in children with and without urinary reflux at baseline
  6. Adherence to antibiotic prophylaxis in the control group
  7. Absolute risk difference of first fUTI with circumcision alone versus circumcision and antibiotic prophylaxis;and antibiotic prophylaxis alone respectively.

Investigational products

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

Test 3

AUGMENTIN 100 mg/12,50 mg par ml NOURRISSONS, poudre pour suspension buvable en flacon (rapport amoxicilline/acide clavulanique : 8/1)

PRD11464168 · Product

Active substance
Amoxicillin
Substance synonyms
AMOXICILLINE, AMOXICILLINUM
Pharmaceutical form
ORAL SUSPENSION
Route of administration
ORAL
Max daily dose
20 mg/kg milligram(s)/kilogram
Max total dose
14600 mg/kg milligram(s)/kilogram
Max treatment duration
24 Month(s)
Authorisation status
Authorised
ATC code
J01CR02 — AMOXICILLIN AND ENZYME INHIBITOR
Marketing authorisation
6 997 824 6
MA holder
LABORATOIRE GLAXOSMITHKLINE
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

ALFATIL 125 mg/5 ml poudre pour suspension buvable

PRD1167506 · Product

Active substance
Cefaclor
Pharmaceutical form
ORAL SUSPENSION
Route of administration
ORAL
Max daily dose
10 mg/kg milligram(s)/kilogram
Max total dose
280 mg/kg milligram(s)/kilogram
Max treatment duration
28 Day(s)
Authorisation status
Authorised
ATC code
J01DC04 — -
Marketing authorisation
34009 323 324 2 7
MA holder
LABORATOIRES ETHYPHARM
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Bactrim 40 mg/ml + 8 mg/ml mikstur, suspensjon

PRD8059132 · Product

Active substance
Sulfamethoxazole
Pharmaceutical form
ORAL SUSPENSION
Route of administration
ORAL
Max daily dose
15 mg/kg milligram(s)/kilogram
Max total dose
10950 mg/kg milligram(s)/kilogram
Max treatment duration
24 Month(s)
Authorisation status
Authorised
ATC code
J01EE01 — SULFAMETHOXAZOLE AND TRIMETHOPRIM
Marketing authorisation
5668
MA holder
EUMEDICA PHARMACEUTICALS GMBH
MA country
Norway
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Bordeaux

27 Total trials 14 Recruiting 6 Ended
Academic / Non-commercial
Sponsor organisation
Centre Hospitalier Universitaire De Bordeaux
Address
12 Rue Dubernat, Cs 91286 Cs 91286
City
Talence
Postcode
33400
Country
France

Scientific contact point

Organisation
Centre Hospitalier Universitaire De Bordeaux
Contact name
Investigateur coordonnateur

Public contact point

Organisation
Centre Hospitalier Universitaire De Bordeaux
Contact name
Investigateur coordonnateur

Locations

1 EU/EEA country · 13 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Authorised, recruitment pending 163 13
Rest of world — 0 —

Investigational sites

France

13 sites · Authorised, recruitment pending
CHU Besancon
chirurgie infantile, 3 Boulevard Alexander Fleming, Cs 81816, Besancon Cedex
Centre Hospitalier Universitaire De Rennes
chirurgie infantile, 16 Boulevard De Bulgarie, Bp 90349, Rennes
Centre Hospitalier Universitaire De Montpellier
chirurgie infantile, 191 Avenue Du Doyen Gaston Giraud, 34295, Montpellier Cedex 5
Assistance Publique Hopitaux De Paris
chirurgie infantile, 26 Avenue Du Docteur Arnold Netter, 75012, Paris
Centre Hospitalier Universitaire De Toulouse
chirurgie infantile, 330 Avenue De Grande Bretagne, 31059, Toulouse Cedex 9
Centre Hospitalier Universitaire Reims
chirurgie infantile, 45 Rue Cognacq Jay, 51092, Reims Cedex
Centre Hospitalier Universitaire De La Reunion
Chirurgie infantile, Allee Des Topazes, Cs 11021, St Denis
Assistance Publique Hopitaux De Paris
chirurgie infantile, 149 Rue De Sevres, 75015, Paris
Centre Hospitalier Et Universitaire De Limoges
chirurgie infantile, 2 Avenue Martin Luther King, 87042, Limoges Cedex 1
Centre Hospitalier Universitaire De Nantes
chirurgie infantile, 38 Boulevard Jean Monnet, 44000, Nantes
Centre Hospitalier Universitaire De Bordeaux
chirurgie infantile, 12 Rue Dubernat, Cs 91286, Talence
Centre Hospitalier Regional De Marseille
chirurgie infantile, 264 Rue Saint Pierre, 13005, Marseille
Assistance Publique Hopitaux De Paris
chirurgie infantile, 48 Boulevard Serurier, 75019, Paris

Results and documents

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

Documents 12 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol 2024-519166-48-01_public 2.00
Protocol (for publication) D2_Protocol modification n1_2024-519166-48-01 1.00
Recruitment arrangements (for publication) K1_Recruitment Arrangements 2024-519166-48-01 1.1
Recruitment arrangements (for publication) K1_Recruitment Arrangements 2024-519166-48-01_TC 1.1
Recruitment arrangements (for publication) K2_Document additionnel 2024-519166-48-01 1.00
Subject information and informed consent form (for publication) L1_SIS and ICF_Prospective-Parental authorities 1.2
Subject information and informed consent form (for publication) L1_SIS and ICF_Retrospective-Parental authorities 1.2
Subject information and informed consent form (for publication) L2_Other subject information material_Memorandum 1.00
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_ALFATIL_125mg-5ml 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_AUGMENTIN_100mg-12-5ml 1.00
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_BACTRIM_40mg-ml 1.00
Synopsis of the protocol (for publication) D1_Protocol synopsis FR 2024-519166-48-01_public 1.2

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-02-11 France Acceptable with conditions
2025-06-02
 2025-06-06
2 SUBSTANTIAL MODIFICATION SM-1 2025-07-02 France Acceptable
2025-08-13
 2025-08-18