Corticosteroids for Children With Febrile Urinary Tract Infections

Phase 3

Completed

• Conditions: Urinary Tract Infection; Acute Urinary Tract Infection
• Interventions: Drug: Placebo; Drug: Dexamethasone

• Registration Number: NCT01391793
• Lead Sponsor: Nader Shaikh

Brief Summary

In this study the investigators will determine whether corticosteroids given at the time of urinary tract infection help prevent permanent damage to the kidneys.

Detailed Description

Because host inflammatory response is the final and most important step in the formation of renal scars, the use of anti-inflammatory agents may be the best strategy to reduce renal scarring. In animal studies, the use of corticosteroids has been shown to be effective in preventing post-pyelonephritic scarring. We will conduct a randomized, double-blind, placebo-controlled trial to determine the efficacy of 3 days of daily adjuvant dexamethasone on the incidence of renal scarring 4 to 6 months after a first febrile urinary tract infection (UTI). We hypothesize that the proportion of children with UTI who develop renal scarring will be lower among children who are treated with both dexamethasone and antibiotics as compared with children treated with antibiotics alone.

Study Timeline

• Study First Submitted: 2011-07-08
• Study First Submitted QC: 2011-07-11
• Study First Posted: 2011-07-12
• Study Start: 2011-09
• Primary Completion: 2018-03-30
• Study Completion: 2018-03-30
• Results First Submitted: 2019-03-28
• Status Verified: 2019-06
• Results First Submitted QC: 2019-06-24
• Last Update Submitted: 2019-06-24
• Results First Posted: 2019-07-02
• Last Update Posted: 2019-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 546

Inclusion Criteria

• Age: 2 months to 6 years
• Pyuria: ≥10 white blood cells per cubic millimeter (WBC/mm3) in an uncentrifuged specimen or ≥5 white blood cells per high power field (WBC/hpf) in a centrifuged specimen or ≥1+ leukocyte esterase (LE) on dipstick
• Fever: documented temperature of at least 101 °F or 38.3°C, measured anywhere on the body either at home or at doctor's office within 24 hours of diagnosis

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Exclusion Criteria

• Other concurrent systemic bacterial infection(s) such as meningitis or pneumonia;
• Planned admission to intensive care unit;
• Known bacteremia;
• Previous protocol defined UTI;
• Known major urinary tract anomalies (severe hydronephrosis, ureterocele, urethral valve, solitary or profoundly small kidney, multicystic dysplastic kidney, neurogenic bladder, pelvic or fused kidney);
• Congenital/acquired immunodeficiency;
• Bag urine collection
• Chronic diseases that could potentially interfere with response to therapy, such as chronic gastrointestinal conditions (i.e. malabsorption, inflammatory bowel disease), liver/kidney failure;
• Allergy to dexamethasone
• Antibiotic use within 7 days of enrollment (except if given in the last 48 hours)
• Systemic use of corticosteroids or other immunomodulating agents within 14 days of enrollment
• History of Kawasaki disease
• Sickle cell disease (not trait)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Adjuvant dexamethasone	Dexamethasone	-

Primary Outcome Measures

Name	Time	Method
The Distribution of Children With Renal Scarring at the Outcome Dimercaptosuccinic Acid (DMSA) Renal Scan	The outcome DMSA scan was 5-24 months from enrollment. The mean number of months was 6.1.	Renal scarring was defined as decreased uptake of tracer with or without loss of contours. Three radiologists independently reviewed for scarring all DMSA scans that were of adequate quality. For a given kidney, the presence or absence of scarring was the diagnosis endorsed by the majority of readers, i.e. 2 of 3. For a given child, if either kidney or both kidneys were diagnosed with scarring by the majority of readers, then the child was determined to have renal scarring.
The Distribution of Children With Severe Renal Scarring at the Outcome Dimercaptosuccinic Acid (DMSA) Renal Scan	The outcome DMSA scan was 5-24 months from enrollment. The mean number of months was 6.1.	Renal scarring was defined as decreased uptake of tracer with or without loss of contours. Scarring was assessed semi-quantitatively by dividing the renal cortex into 12 equal segments. Severe scarring was defined as greater than 4 affected renal segments or global atrophy, i.e. diffuse scarring or shrunken kidney. Three radiologists independently reviewed for scarring all DMSA scans that were of adequate quality. For a given kidney, the presence or absence of severe scarring was the diagnosis endorsed by the majority of readers, i.e. 2 of 3. For a given child, if either kidney or both kidneys were diagnosed with severe scarring by the majority of readers, then the child was determined to have severe renal scarring.

Secondary Outcome Measures

Name	Time	Method
The Mean Proportion of Children With Renal Scarring at the Outcome Dimercaptosuccinic Acid (DMSA) Renal Scan Taken Across the 3 Radiologists	The outcome DMSA scan was 5-24 months from enrollment. The mean number of months was 6.1.	Renal scarring was defined as decreased uptake of tracer with or without loss of contours. Three radiologists independently reviewed for scarring all DMSA scans that were of adequate quality. For each radiologist, for each child, if either kidney or both kidneys were diagnosed with scarring, then the child was determined to have renal scarring. For each radiologist, the proportion of children with scarring in a given treatment group is the number of children diagnosed with scarring divided by the number of children in the treatment group. The mean proportion of children with scarring in a given treatment group is the average proportion taken across the 3 radiologists.

Trial Locations

Locations (6)

Nationwide Children's Hospital in Columbus; 🇺🇸 Columbus, Ohio, United States

Children's Hospital of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Primary Children's Hospital; 🇺🇸 Salt Lake City, Utah, United States

American Family Children's Hospital; 🇺🇸 Madison, Wisconsin, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States

Hasbro Children's Hospital; 🇺🇸 Providence, Rhode Island, United States