PREDICT

PREDICT Trial

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

 

Congenital Abnormalities of Kidney and Urinary Tract (CAKUT) represent the most common human congenital anomalies, and Urinary Tract Infections (UTIs) are among the most frequent invasive bacterial infections in children. Thanks to efficient prenatal screening CAKUT is nowadays typically known from birth, and the population is known to be at increased risk of both UTIs and progressive renal failure and eventual need for renal replacement therapy. However, the causative role of UTIs in the progression of kidney damage in this population is unknown and unpredictable.

Antibiotic prophylaxis is widely used in paediatric practice in children with Vesico-Ureteral Reflux (VUR) to prevent UTIs and consequent kidney damage. Despite recent trials supporting the efficacy of prophylaxis in reducing UTI incidence, many concerns remain regarding the long-term effectiveness and safety of extended antibiotic exposure. Apart from the unproven value of antibiotic prophylaxis in preventing long-term kidney damage, the treatment concept is increasingly controversial in view of the spreading bacterial resistance to antibiotics and potential obesity-promoting metabolic effects of chronic antibiotic exposure, two major public health concerns in Europe.

To provide a definitive answer to those open questions, we have designed a controlled study which follows, from birth onwards, infants with severe VUR in the presence or absence of hypo-dysplasia, randomized for antibiotic prophylaxis or observation.

The primary objective is the evaluation of the effectiveness of antimicrobial prophylaxis in the reduction of symptomatic UTIs in infants with VUR grade III-V, started before the first symptomatic infection.

The secondary goals are the assessment of: symptomatic and febrile UTIs on the appearance and progression of kidney damage and development of renal function; the natural history of renal function and the vesico-ureteral reflux evolution in paediatric patients with congenital kidney or urinary tract anomalies during the first 5 years of life; new renal scars at the 2 and 5-year follow-up DMSA scan; the effect on BMI at 2 and 5 years of age due to prophylactic antibiotic therapy during the first months of life on; gut microbiota alterations induced by continuous antibiotic exposure during the first months of life.

 

Design:

Prospective, controlled, randomized, open label, multicenter trial:
  i) Pre-randomization diagnostic work-up period
  ii) 24-month treatment period following stratification and randomization:
      Group A: no antimicrovial prophylaxis
      Group B: antimicrobial prophylaxis
  iii) 36 months follow-up period for evaluation of kidney damage and renal function at 5 years

Patients enrolled: 240 of 300 planned patients with VUR enrolled to date (11/2018)
Coordinating Center:

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

Participating Centers:ESCAPE group of 40 European Paediatric Nephrology Centers
Contact Information:

giovanni.montini@unimi.it
william.morello@policlinico.mi.it
jessica.serafinelli@policlinico.mi.it
helpdeskpredict@gmail.com

 

Active ESCAPE Participants:

Ali Anarat
 

Lutz Weber