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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02021006
Recruitment Status : Active, not recruiting
First Posted : December 27, 2013
Last Update Posted : August 11, 2020
Sponsor:
Collaborators:
Ministero della Salute, Italy
IL Sogno di Stefano
Information provided by (Responsible Party):
Giovanni Montini, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Tracking Information
First Submitted Date  ICMJE December 1, 2013
First Posted Date  ICMJE December 27, 2013
Last Update Posted Date August 11, 2020
Study Start Date  ICMJE December 2013
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 19, 2013)
urinary tract infections rate [ Time Frame: during the first 24 months from enrolment ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2019)
  • febrile urinary tract infections [ Time Frame: during the first 24 months from enrolment ]
    Febrile urinary tract infections will be strictly monitored in all enrolled patients (both group A and group B). The rate of febrile urinary tract infections in the first 24 months from the enrolment will be compared between 2 groups
  • renal scars [ Time Frame: at 2 years and 5 years from enrolment ]
    the appearance of renal scars in a dimercaptosuccinic acid (DMSA) scan will be detected at 2 and 5 years from enrolment and compared between the 2 groups.
  • serum creatinine (renal function) [ Time Frame: at the enrolment,1 year, 2 years, 3 years, 4 years, 5 years ]
    The renal function (serum creatinine) will be monitored for all enrolled patients to explore the appearance and progression of renal damage
  • hypertension [ Time Frame: at 4, 8, 12, 18, 24, 36, 48, 60 months from enrolment ]
    the appearance of hypertension will be monitored at every visit in all enrolled children
  • proteinuria [ Time Frame: at 4, 8, 12, 18, 24, 36, 48, 60 months from enrolment ]
    the appearance of proteinuria will be monitored at every visit in all enrolled children
  • body mass index [ Time Frame: at 2 and 5 years from enrolment ]
    body mass index will be evaluated at 2 and 5 years of follow-up and it will be correlated to the use of antibiotic prophylaxis
  • serum cystatin C (renal function) [ Time Frame: at the enrolment,1 year, 2 years, 3 years, 4 years, 5 years ]
    The renal function (serum cystatin-C) will be monitored for all enrolled patients to explore the appearance and progression of renal damage
  • modification in gut microbiota induced by continuous antibiotic exposure during the first months of life [ Time Frame: at the enrollment, 4 months, 8 months, 12 months, 2 years, 3 years, 4 years, 5 years ]
    A stool sample will be collected, frozen and stored for gut microbiota and resistome profile analysis
Original Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2013)
  • febrile urinary tract infections [ Time Frame: during the first 24 months from enrolment ]
    Febrile urinary tract infections will be strictly monitored in all enrolled patients (both group A and group B). The rate of febrile urinary tract infections in the first 24 months from the enrolment will be compared between 2 groups
  • renal scars [ Time Frame: at 2 years and 5 years from enrolment ]
    the appearance of renal scars in a dimercaptosuccinic acid (DMSA) scan will be detected at 2 and 5 years from enrolment and compared between the 2 groups.
  • serum creatinine (renal function) [ Time Frame: at the enrolment,1 year, 2 years, 3 years, 4 years, 5 years ]
    The renal function (serum creatinine) will be monitored for all enrolled patients to explore the appearance and progression of renal damage
  • hypertension [ Time Frame: at 4, 8, 12, 18, 24, 36, 48, 60 months from enrolment ]
    the appearance of hypertension will be monitored at every visit in all enrolled children
  • proteinuria [ Time Frame: at 4, 8, 12, 18, 24, 36, 48, 60 months from enrolment ]
    the appearance of proteinuria will be monitored at every visit in all enrolled children
  • body mass index [ Time Frame: at 2 and 5 years from enrolment ]
    body mass index will be evaluated at 2 and 5 years of follow-up and it will be correlated to the use of antibiotic prophylaxis
  • serum cystatin C (renal function) [ Time Frame: at the enrolment,1 year, 2 years, 3 years, 4 years, 5 years ]
    The renal function (serum cystatin-C) will be monitored for all enrolled patients to explore the appearance and progression of renal damage
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Antibiotic Prophylaxis and Renal Damage In Congenital Abnormalities of the Kidney and Urinary Tract
Official Title  ICMJE Antibiotic Prophylaxis and Renal Damage In Congenital Abnormalities of the Kidney and Urinary Tract
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.

Detailed Description

Bacterial urinary tract infections (UTI) are common in young children. The presence of fever is considered to be a marker of renal parenchymal involvement. Renal damage during the acute phase of infection may lead to scarring, yet the role that scarring plays in the appearance of chronic kidney failure is unknown. It is also unclear what influence scars have on the natural course of kidney function, especially in children with renal hypodysplasia, with or without vesicoureteral reflux (VUR). Renal hypodysplasia is the most common cause for dialysis and transplantation in the pediatric population.

Patients suffering from recurrent UTIs and VUR have often undergone corrective surgery. For many years, it was also thought necessary to prescribe long-term antibiotic prophylaxis to all children with VUR. These treatment strategies were based on the ideas and opinions of the experts, rather than on hard scientific evidence. As regards the prevention of recurrent UTIs and the subsequent development of renal scarring, a long-term international study on Reflux was not able to demonstrate that surgical correction is more effective than antibiotic prophylaxis. Very little data is available regarding the use of long-term antibiotic prophylaxis in children with high grade reflux with or without renal hypodysplasia.

The use of antibiotics during the first few months of life has been associated with a significant increase in body mass index (BMI). Even though this effect is probably limited, it could have a significant impact on public health given the widespread use of antibiotics and due to the considerable increase in cases of pediatric and adult obesity seen over the last few years.

In spite of the lack of evidence, the use of prophylaxis is largely routine practice in most centres. Therefore, a randomized study is necessary in order to evaluate whether prophylaxis reduces the risk of symptomatic infections and subsequent renal damage.

To assess the role of prophylaxis in patient with high grade vesicoureteral reflux we will perform a multicentre, prospective, randomized, controlled, open-label, study.

Patients enrolled will be randomized in two groups:

Group A: no antibiotic prophylaxis. Group B: antibiotic prophylaxis for 24 months. The choice of which antibiotic to prescribe from the list below is left to the discretion of each investigator, on the basis of local antibiotic resistance patterns.

  • nitrofurantoin 1.5-2 mg/kg per day
  • amoxicilline/clavulanic acid 15 mg/kg per day (dose expressed in units equivalent to amoxicillin)
  • cefixime 2 mg/kg per day
  • trimethoprim/sulfamethoxazole 2.5 mg/kg per day (dose expressed in units equivalent to trimethoprim)

The study is comprised of:

  • Phase 1: Pre-randomization - screening tests to determine eligibility for the trial.
  • Phase 2: Active treatment - this phase follows randomization and foresees 24 months of antibiotic prophylaxis for Group B and clinical surveillance for Group A.
  • Phase 3: Follow-up - a further 36 months of clinical, laboratory and instrumental evaluation of renal function and the progression of renal damage for a total follow-up period of 5 years
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Vesicoureteral Reflux
  • Renal Hypodysplasia, Nonsyndromic, 1
  • Chronic Kidney Disease
Intervention  ICMJE
  • Drug: nitrofurantoin

    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)
    Other Name: Furadantin
  • Other: No prophylaxis
    children will be followed, but no antibiotic prophylaxis will be administered
  • Drug: Amoxicillin-Potassium Clavulanate Combination

    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)
    Other Name: amoxicilline/clavulanic acid, augmentin, clavulin
  • Drug: Trimethoprim/sulfamethoxazole

    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)
    Other Name: bactrim
  • Drug: Cefixime

    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)
    Other Name: cefixoral
Study Arms  ICMJE
  • Active Comparator: ANTIBIOTIC PROPHYLAXIS

    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)
    Interventions:
    • Drug: nitrofurantoin
    • Drug: Amoxicillin-Potassium Clavulanate Combination
    • Drug: Trimethoprim/sulfamethoxazole
    • Drug: Cefixime
  • Experimental: NO PROPHYLAXIS
    Children in this arm will not take antibiotic prophylaxis. Patients in this arm will do clinical/instrumental follow-up for 5 years
    Intervention: Other: No prophylaxis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 10, 2020)
292
Original Estimated Enrollment  ICMJE
 (submitted: December 19, 2013)
436
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Month to 4 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02021006
Other Study ID Numbers  ICMJE PREDICT trial
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Giovanni Montini, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Study Sponsor  ICMJE Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Collaborators  ICMJE
  • Ministero della Salute, Italy
  • IL Sogno di Stefano
Investigators  ICMJE
Study Chair: Giovanni Montini, MD Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan
Study Director: Franz Schaefer, Professor Center for Pediatrics and Adolescent Medicine Division of Pediatric Nephrology, Heidelberg, Germany
Principal Investigator: 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
PRS Account Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP