Corticosteroids for Children With Febrile Urinary Tract Infections (STARRS)

• ClinicalTrials.gov Identifier: NCT01391793
• Recruitment Status: Completed
• First Posted: July 12, 2011
• Results First Posted: July 2, 2019
• Last Update Posted: July 2, 2019
• Sponsor: Nader Shaikh
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Nader Shaikh, University of Pittsburgh

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Urinary Tract Infection; Urinary Tract Infection	Drug: Placebo; Drug: Dexamethasone	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 546 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Corticosteroids for Children With Febrile Urinary Tract Infections
• Study Start Date: September 2011
• Actual Primary Completion Date: March 30, 2018
• Actual Study Completion Date: March 30, 2018

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Adjuvant dexamethasone	Drug: Dexamethasone; 0.15 mg/kg/dose twice daily for 3 days; Other Names: Prelone; Orapred; Corticosteroid
Placebo Comparator: Placebo	Drug: Placebo; Twice daily for 3 days; Other Name: Inactive medicine

Outcome Measures

Primary Outcome Measures :

1. The Distribution of Children With Renal Scarring at the Outcome Dimercaptosuccinic Acid (DMSA) Renal Scan [ Time Frame: 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.
2. The Distribution of Children With Severe Renal Scarring at the Outcome Dimercaptosuccinic Acid (DMSA) Renal Scan [ Time Frame: 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 :

1. The Mean Proportion of Children With Renal Scarring at the Outcome Dimercaptosuccinic Acid (DMSA) Renal Scan Taken Across the 3 Radiologists [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 2 Months to 6 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

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)

Contacts and Locations

Locations

United States, District of Columbia

Children's National Medical Center

Washington, District of Columbia, United States, 20010

United States, Ohio

Nationwide Children's Hospital in Columbus

Columbus, Ohio, United States, 43205

United States, Pennsylvania

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15224

United States, Rhode Island

Hasbro Children's Hospital

Providence, Rhode Island, United States, 02903

United States, Utah

Primary Children's Hospital

Salt Lake City, Utah, United States, 84113

United States, Wisconsin

American Family Children's Hospital

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

Nader Shaikh

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Nader Shaikh, MD; University of Pittsburgh

  Study Documents (Full-Text)

Documents provided by Nader Shaikh, University of Pittsburgh:

Study Protocol and Statistical Analysis Plan  [PDF] May 29, 2019

Informed Consent Form  [PDF] November 17, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Shaikh N, Liu H, Kurs-Lasky M, Forster CS. Biomarkers for febrile urinary tract infection in children. Pediatr Nephrol. 2022 Jan;37(1):171-177. doi: 10.1007/s00467-021-05173-x. Epub 2021 Jul 12.

Shaikh N, Shope TR, Hoberman A, Muniz GB, Bhatnagar S, Nowalk A, Hickey RW, Michaels MG, Kearney D, Rockette HE, Charron M, Lim R, Majd M, Shalaby-Rana E, Kurs-Lasky M, Cohen DM, Wald ER, Lockhart G, Pohl HG, Martin JM. Corticosteroids to prevent kidney scarring in children with a febrile urinary tract infection: a randomized trial. Pediatr Nephrol. 2020 Nov;35(11):2113-2120. doi: 10.1007/s00467-020-04622-3. Epub 2020 Jun 15.

• Responsible Party: Nader Shaikh, Assistant Professor of Pediatrics, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT01391793
• Other Study ID Numbers: R01DK087870 ( U.S. NIH Grant/Contract ); R01DK087870 ( U.S. NIH Grant/Contract )
• First Posted: July 12, 2011
• Results First Posted: July 2, 2019
• Last Update Posted: July 2, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Nader Shaikh, University of Pittsburgh:

Renal scarring; Dexamethasone; Child; Corticosteroids; Pediatric; Urinary tract infection; Escherichia Coli Urinary Tract Infection

Additional relevant MeSH terms:

Infections; Communicable Diseases; Urinary Tract Infections; Disease Attributes; Pathologic Processes; Urologic Diseases; Dexamethasone; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents