Clinical trial NCT02034851: Dexamethasone Administration in 1st Episode of Febrile Urinary Tract Infection
Official title: Phase 3- Dexamethasone Administration in 1st Episode of Febrile Urinary Tract Infection Episode as Renal Damage Prevention Strategy. DEXCAR
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Pyelonephritis
Keywords: Acute pyelonephritis
Renal scarring
Dexamethasone
Children
Corticoids
Complementary treatment
Prevention strategy
Lead sponsor: Institut Investigacio Sanitaria Pere Virgili
Sponsor class: OTHER
Collaborators: name: Hospital Universitari Sant Joan de Reus
name: Hospital Universitari Joan XXIII de Tarragona.
name: Pius Hospital de Valls
name: Hospital Arnau de Vilanova
name: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Maternal-Infantil Vall d´Hebron Hospital
name: Hospital General Universitario Santa Lucía
name: University Rovira i Virgili
First posted: 2014-01-14
Enrollment: 183
Sex: ALL
Minimum age (years): 2
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Those children between 2 months and 14 years with a provable acute pyelonephritis that fulfill the hospitalization criteria defined in the Spanish Clinical practice guide.

Brief summary: Hypothesis: Administration of corticoids (dexamethasone) together with the conventional antibiotherapy in the acute phase of a febrile urinary tract infection could reduce the risk of renal scarring after 6 months of the primo-infection.

Primary objectives:To evaluate the reduction in incidence of renal scarring after 6 months of a acute pyelonephritis between the control group (conventional therapy plus placebo) and intervention group (conventional therapy plus dexamethasone.

Design: Multicentre randomized clinical trial,placebo controled, including children between 2 months and 14 years with a acute pyelonephritis proven by a acute phase DMSA (dimethylsuccinic acid ). A total of 180 children in to parallel groups (intervention and placebo) will be included.

Detailed description: The urinary tract infection (UTI) is one of the most common bacterial infections in children. These infections can be grouped clinically as asymptomatic bacteriuria , cystitis (lower urinary tract infection ) and acute pyelonephritis (APN ) when the infection reaches the upper urinary tract. This classification is of great clinical relevance because while cystitis is usually a benign condition without further complications , the APN is associated with an increased risk of kidney damage, acquired through renal scarring . Renal scarring is a consequence of the inflammatory and immune response that is triggered to eradicate the bacteria involved in the UTI. Parenchymal infection can be solved , but there are a number of poorly understood factors that may perpetuate inflammation and this would promote the formation of scar nephritis. One of the most relevant factors involved in the renal scarring development are the production of inflammatory mediators (complement proteins, bactericidal peptides, cytokines such as IL6 and IL8, chemokines, and adhesion molecules defensins). Thus, it is obvious to think that the use of anti-inflammatory drugs may prevent the release of these mediators and the development of permanent kidney damage.

Intervention: the two parallel groups will receive the conventional therapy plus:

1. dexamethasone: 0'30 mg per kg every 12 hours during 3 days.
2. placebo (physiological saline)at the same dosing regimen.

Centralized lecture of the late DMSA after 6 months of the pyelonephritis episode will be performed. Renal scarring presence and grade will be reported.

Eligibility criteria: Inclusion Criteria:

Those children between 2 months and 14 years with a provable acute pyelonephritis that fulfill the hospitalization criteria defined in the Spanish Clinical practice guide. Briefly:

* age under 3 months.
* general affectation, toxic appearance.
* vomiting or oral intolerance.
* dehydration, bad peripheric perfusion.
* or other intermedia situations that include:

  1. high fever (\>38.5 Celsius) in 3-6 month old children.
  2. unusual germ risk factors.
  3. family history of vesicoureteral reflux.
  4. recurrent febrile urinary infections. With absence of a previous renal scarring objectivated after a DMSA.
  5. high elevation of acute phase reactants.

Exclusion Criteria:

* those eligible patients that do not fulfill the hospitalization criteria.
* patients with a procalcitonin under 0.05 ng per ml.
* patients with previous uropathy or renal scarring
* patients allergic to dexamethasone.
* endocrinologic disease.
* history of cancer.
* serious illness.
* immunosuppressor treatment.
* previous treatment with corticoids (continuous oral or parenteral treatment) during the last 2 months.
* the patient included in the study that do not present pyelonephritis after the acute phase DMSA evaluation will be excluded.
* the patient included in the study that suffered a second pyelonephritis episode during the following 6 months (before the second DMSA evaluation) will be excluded for the primary output analyses.

Primary outcomes:
measure: renal scarring
timeFrame: 6 month after the acute pyelonephritis episode
Secondary outcomes:
Other outcomes:
Locations:
city: Cartagena
country: Spain
facility: Hospital General Universitario Santa Lucía de Cartagena
state: Murica
city: Reus
country: Spain
facility: Iispv- Hospital Sant Joan de Reus
state: Tarragona
city: Valls
country: Spain
facility: Pius Hospital de Valls
state: Tarragona
city: Barcelona
country: Spain
facility: Hospital Maternoinfantil Vall D'Hebron
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau de Barcelona
city: Lleida
country: Spain
facility: Hospital Arnau de Vilanova de Lleida
city: Tarragona
country: Spain
facility: Iispv-Hospital Joan Xxii de Tarragona
Study officials:
affiliation: IISPV- URV-Hospital Universitari Sant Joan de Reus- Research unit in pediatrics, nutrition and human development
name: Escribano J Joaquin, PhD MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IISPV-URV- Hospital Universitari Joan XXIII de Tarragona-Research unit in pediatrics, nutrition and human development
name: Closa R Ricardo, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: IISPV-URV-Research unit in pediatrics, nutrition and human development
name: Ferré N Natalia, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: HOSPITAL ARNAU DE VILANOVA DE LLEIDA
name: Ibars Z Zaira, MD PhD
role: STUDY_DIRECTOR
affiliation: HOSPITAL DE LA SANTA CREU I SANT PAU, DE BARCELONA
name: Maria Gloria MG Fraga, MD PhD
role: STUDY_DIRECTOR
affiliation: HOSPITAL MATERNOINFANTIL VALL D'HBRON, BARCELONA
name: Madrid A Alvaro, MD PhD
role: STUDY_DIRECTOR
affiliation: Pius Hospital de Valls
name: Samper M Manuel, MD PhD
role: STUDY_DIRECTOR
affiliation: HOSPITAL GENERAL UNIVERSITARIO SANTA LUCÍA DE CARTAGENA
name: Gonzalez JD Juan David, MD PhD
role: STUDY_DIRECTOR
affiliation: HOSPITAL JOAN XXII DE TARRAGONA
name: Parada E Esther, MD PhD
role: STUDY_DIRECTOR
References:
citation: Rius-Gordillo N, Ferre N, Gonzalez JD, Ibars Z, Parada-Ricart E, Fraga MG, Chocron S, Samper M, Vicente C, Fuertes J, Escribano J; DEXCAR Study Group. Dexamethasone to prevent kidney scarring in acute pyelonephritis: a randomized clinical trial. Pediatr Nephrol. 2022 Sep;37(9):2109-2118. doi: 10.1007/s00467-021-05398-w. Epub 2022 Jan 18.