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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
Sponsor:
Collaborators:
Ministero della Salute, Italy
IL Sogno di Stefano
Information provided by (Responsible Party):
Giovanni Montini, Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
ClinicalTrials.gov Identifier:
NCT02021006
First received: December 1, 2013
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Vesicoureteral Reflux
Renal Hypodysplasia, Nonsyndromic, 1
Chronic Kidney Disease
Drug: nitrofurantoin
Other: No prophylaxis
Drug: Amoxicillin-Potassium Clavulanate Combination
Drug: Trimethoprim/sulfamethoxazole
Drug: Cefixime
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Antibiotic Prophylaxis and Renal Damage In Congenital Abnormalities of the Kidney and Urinary Tract

Resource links provided by NLM:


Further study details as provided by Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi:

Primary Outcome Measures:
  • urinary tract infections rate [ Time Frame: during the first 24 months from enrolment ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • febrile urinary tract infections [ Time Frame: during the first 24 months from enrolment ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    The renal function (serum cystatin-C) will be monitored for all enrolled patients to explore the appearance and progression of renal damage


Estimated Enrollment: 436
Study Start Date: December 2013
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
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
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
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
Other: No prophylaxis
children will be followed, but no antibiotic prophylaxis will be administered

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
  Eligibility

Ages Eligible for Study:   1 Month to 4 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age between 1 and 4 months
  • 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, apart from 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02021006

Contacts
Contact: Giovanni Montini, MD +390516364617 giovanni.montini@aosp.bo.it

Locations
Italy
Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi Recruiting
Bologna, Italy, 40138
Contact: Giovanni Montini, MD    +390516364617    giovanni.montini@aosp.bo.it   
Principal Investigator: Giovanni Montini, MD         
Sponsors and Collaborators
Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
Ministero della Salute, Italy
IL Sogno di Stefano
Investigators
Study Chair: Giovanni Montini, MD Nefrologia Pediatrica Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
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: Alberto Edefonti, MD Pediatric Nephrology and Dialysis Unit, Fondazione IRCCS Ca' Granda, Milano, Italy
Principal Investigator: Enrico Verrina, MD UOC Nefrologia, Dialisi e Trapianto, IRCCS Giannina Gaslini, Genova, Italy
Principal Investigator: William Morello, MD Nefrologia Pediatrica Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
Principal Investigator: Piotr Czarniak, MD Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk - Poland
  More Information

No publications provided

Responsible Party: Giovanni Montini, MD, Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
ClinicalTrials.gov Identifier: NCT02021006     History of Changes
Other Study ID Numbers: PREDICT trial
Study First Received: December 1, 2013
Last Updated: January 14, 2014
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi:
antibiotic prophylaxis
vesicoureteral reflux
congenital abnormalities of kidney
renal hypodysplasia
chronic kidney disease

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Congenital Abnormalities
Vesico-Ureteral Reflux
Urologic Diseases
Renal Insufficiency
Urinary Bladder Diseases
Trimethoprim
Nitrofurantoin
Clavulanic Acid
Cefixime
Amoxicillin-Potassium Clavulanate Combination
Clavulanic Acids
Sulfamethoxazole
Amoxicillin
Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents, Urinary
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antitubercular Agents

ClinicalTrials.gov processed this record on September 30, 2014