Antibiotic Prophylaxis and Renal Damage In Congenital Abnormalities of the Kidney and Urinary Tract

NCT02021006 | Unknown Phase 3 DMC

• 1 other identifier: PREDICT trial
• Study Type: interventional
• Target: 292
• Locations: 1 country
• Sites: 1

Brief Summary

The exact role of urinary tract infection in the appearance of chronic kidney disease is unclear. Children with congenital malformations of kidney and urinary tract have the higher risk of impairment of renal function. To understand if the use of antibiotic prophylaxis can reduce the risk of urinary tract infection in children with these malformations, this study will randomize children in two groups. Group A will not take antibiotic prophylaxis, Group B will take antibiotic prophylaxis for 2 years. This study will assess if antibiotic prophylaxis reduce the risk of urinary tract infections in these children and if urinary tract infections influence the appearance of renal damage. Our hypothesis is that prophylaxis reduce the risk of infection in severe vesicoureteral reflux and that urinary tract infections, in morphologically normal kidneys, will not result in chronic renal failure.

Conditions

Vesicoureteral Reflux; Renal Hypodysplasia, Nonsyndromic, 1; Chronic Kidney Disease

Keywords

antibiotic prophylaxis; vesicoureteral reflux; congenital abnormalities of kidney; renal hypodysplasia; chronic kidney disease

Outcome Measures

Primary Outcomes (1)

• urinary tract infections rate

  Urinary tract infections will be strictly monitored in all enrolled patients (both group A and group B). The rate of urinary tract infections in the first 24 months from the enrolment will be compared between 2 groups

  during the first 24 months from enrolment

Secondary Outcomes (8)

• febrile urinary tract infections

  during the first 24 months from enrolment

• renal scars

  at 2 years and 5 years from enrolment

• serum creatinine (renal function)

  at the enrolment,1 year, 2 years, 3 years, 4 years, 5 years

• hypertension

  at 4, 8, 12, 18, 24, 36, 48, 60 months from enrolment

• proteinuria

  at 4, 8, 12, 18, 24, 36, 48, 60 months from enrolment

Study Arms (2)

ANTIBIOTIC PROPHYLAXIS

ACTIVE COMPARATOR

Children in this arm will take antibiotic prophylaxis for 2 years. Patients in this arm will do clinical/instrumental follow-up for 5 years. The antibiotic for prophylaxis will be chosen by Physicians according to the local resistance spectrum of bacteria responsible of UTIs Physicians can chose one the following schedules: * nitrofurantoin 1.5-2 mg/kg per day * Amoxicillin-Potassium Clavulanate Combination 15 mg/kg per day (dose expressed in units equivalent to amoxicilline) * cefixime 2 mg/kg per day * trimethoprim/sulfamethoxazole 2.5 mg/kg per day (dose expressed in units equivalent to trimethoprim)

Drug: nitrofurantoin; Drug: Amoxicillin-Potassium Clavulanate Combination; Drug: Trimethoprim/sulfamethoxazole; Drug: Cefixime

NO PROPHYLAXIS

EXPERIMENTAL

Children in this arm will not take antibiotic prophylaxis. Patients in this arm will do clinical/instrumental follow-up for 5 years

Other: No prophylaxis

Interventions

nitrofurantoin DRUG

antibiotic prophylaxis of urinary tract infections The antibiotic for prophylaxis will be chosen by Physicians according to the local resistance spectrum of bacteria responsible of UTIs Physicians can chose one the following schedules: * nitrofurantoin 1.5-2 mg/kg per day * amoxicilline/clavulanic acid 15 mg/kg per day (dose expressed in units equivalent to amoxicilline) * cefixime 2 mg/kg per day * trimethoprim/sulfamethoxazole 2.5 mg/kg per day (dose expressed in units equivalent to trimethoprim)

Also known as: Furadantin

ANTIBIOTIC PROPHYLAXIS

No prophylaxis OTHER

children will be followed, but no antibiotic prophylaxis will be administered

NO PROPHYLAXIS

Amoxicillin-Potassium Clavulanate Combination DRUG

antibiotic prophylaxis of urinary tract infections The antibiotic for prophylaxis will be chosen by Physicians according to the local resistance spectrum of bacteria responsible of UTIs Physicians can chose one the following schedules: * nitrofurantoin 1.5-2 mg/kg per day * amoxicilline/clavulanic acid 15 mg/kg per day (dose expressed in units equivalent to amoxicilline) * cefixime 2 mg/kg per day * trimethoprim/sulfamethoxazole 2.5 mg/kg per day (dose expressed in units equivalent to trimethoprim)

Also known as: amoxicilline/clavulanic acid, augmentin, clavulin

ANTIBIOTIC PROPHYLAXIS

Trimethoprim/sulfamethoxazole DRUG

antibiotic prophylaxis of urinary tract infections The antibiotic for prophylaxis will be chosen by Physicians according to the local resistance spectrum of bacteria responsible of UTIs Physicians can chose one the following schedules: * nitrofurantoin 1.5-2 mg/kg per day * amoxicilline/clavulanic acid 15 mg/kg per day (dose expressed in units equivalent to amoxicilline) * cefixime 2 mg/kg per day * trimethoprim/sulfamethoxazole 2.5 mg/kg per day (dose expressed in units equivalent to trimethoprim)

Also known as: bactrim

ANTIBIOTIC PROPHYLAXIS

Cefixime DRUG

antibiotic prophylaxis of urinary tract infections The antibiotic for prophylaxis will be chosen by Physicians according to the local resistance spectrum of bacteria responsible of UTIs Physicians can chose one the following schedules: * nitrofurantoin 1.5-2 mg/kg per day * amoxicilline/clavulanic acid 15 mg/kg per day (dose expressed in units equivalent to amoxicilline) * cefixime 2 mg/kg per day * trimethoprim/sulfamethoxazole 2.5 mg/kg per day (dose expressed in units equivalent to trimethoprim)

Also known as: cefixoral

ANTIBIOTIC PROPHYLAXIS

Eligibility Criteria

• Age: 1 Month - 4 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age between 1 and 4 months (\> 4 weeks and \<20 weeks of post-natal age)
• Gestational age \> 35 weeks
• Glomerular filtration rate (calculated according to Schwartz) \> 15 ml/min/1.73 m2
• No previous symptomatic UTI
• Imaging Diagnostic work-up completed and presence of grade III to V vesicoureteral reflux
• Informed consent of parents

You may not qualify if:

• Age \<1 and \>4 months
• Gestational age \< 35 weeks
• Glomerular filtration rate (calculated according to Schwartz) \< 15 ml/min/1.73 m2 at three months of age
• Patients with neurogenic bladder, myelomeningocele, ureteropelvic junction and/or ureterovesical junction obstruction, or other malformations leading to potential voiding disturbances.
• Presence of urethral valves
• Patients with no or low grade reflux (grade I and II).
• Hypersensitivity to the all the utilized antimicrobial agent
• Children with serious clinical conditions which, according to the investigator, prevent them from being included in the study cohort.
• Use of experimental drugs in the month previous to the beginning of the study
• Children unable to follow the established protocol procedures or whose parents are unable to sign the informed consent.

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead
• Ministero della Salute, Italy: collaborator
• IL Sogno di Stefano: collaborator

Study Sites (1)

Pediatric Nephrology Dialysis and Transplant Unit IRCCS Ca'Granda

Milan, 20122, Italy

Location

Related Publications (1)

• Morello W, Baskin E, Jankauskiene A, Yalcinkaya F, Zurowska A, Puccio G, Serafinelli J, La Manna A, Krzemien G, Pennesi M, La Scola C, Becherucci F, Brugnara M, Yuksel S, Mekahli D, Chimenz R, De Palma D, Zucchetta P, Vajauskas D, Drozdz D, Szczepanska M, Caliskan S, Lombet J, Minoli DG, Guarino S, Gulleroglu K, Ruzgiene D, Szmigielska A, Barbi E, Ozcakar ZB, Kranz A, Pasini A, Materassi M, De Rechter S, Ariceta G, Weber LT, Marzuillo P, Alberici I, Taranta-Janusz K, Caldas Afonso A, Tkaczyk M, Catala M, Cabrera Sevilla JE, Mehls O, Schaefer F, Montini G; PREDICT Study Group. Antibiotic Prophylaxis in Infants with Grade III, IV, or V Vesicoureteral Reflux. N Engl J Med. 2023 Sep 14;389(11):987-997. doi: 10.1056/NEJMoa2300161. Epub 2023 Sep 12.

  PMID: 37702442 DERIVED

MeSH Terms

Conditions

Vesico-Ureteral Reflux; Renal Hypodysplasia, Nonsyndromic, 1; Renal Insufficiency, Chronic

Interventions

Nitrofurantoin; Amoxicillin-Potassium Clavulanate Combination; Amoxicillin; Clavulanic Acid; Trimethoprim, Sulfamethoxazole Drug Combination; Cefixime

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency; Kidney Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitrofurans; Nitro Compounds; Organic Chemicals; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Clavulanic Acids; beta-Lactams; Lactams; Amides; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Combinations; Pharmaceutical Preparations; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Trimethoprim; Pyrimidines; Cefotaxime; Cephacetrile; Cephalosporins; Thiazines

Study Officials

• Giovanni Montini, MD

  Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan

  STUDY CHAIR

• Franz Schaefer, Professor

  Center for Pediatrics and Adolescent Medicine Division of Pediatric Nephrology, Heidelberg, Germany

  STUDY DIRECTOR

• Otto Mehls, Professor

  Center for Pediatrics and Adolescent Medicine Division of Pediatric Nephrology, Heidelberg, Germany

  PRINCIPAL INVESTIGATOR

• Lutz T. Weber, Professor

  Ärztlicher Leiter der Kindernephrologie Klinik und Poliklinik für Kinder- und Jugendmedizin Uniklinik Köln - Köln

  PRINCIPAL INVESTIGATOR

• Aleksandra M Zurowska, Professor

  Medical University of Gdansk, Department Paediatric & Adolescent Nephrology & Hypertension - Gdansk - Poland

  PRINCIPAL INVESTIGATOR

• Fatos Yalcinkaya, Professor

  Department of Pediatric Nephrology, School of Medicine, Ankara University, Ankara, Turkey

  PRINCIPAL INVESTIGATOR

• Esra Baskin, Professor

  Paediatric Nephrology Division, Department of Paediatrics, Faculty of Medicine, Baskent University, Ankara, Turkey

  PRINCIPAL INVESTIGATOR

• Enrico Verrina, MD

  UOC Nefrologia, Dialisi e Trapianto, IRCCS Giannina Gaslini, Genova, Italy

  PRINCIPAL INVESTIGATOR

• William Morello, MD

  Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan

  PRINCIPAL INVESTIGATOR

• Piotr Czarniak, MD

  Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk - Poland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: December 1, 2013
• First Posted: December 27, 2013
• Study Start: December 1, 2013
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2025
• Last Updated: September 28, 2023

Record last verified: 2023-09

Locations

IT (1)