Efficacy of Corticosteroids in Reducing Renal Scarring in Acute Pyelonephritis in Children

Efficacy of Corticosteroids in Reducing Renal Scarring in Acute Pyelonephritis in Children:A Multi-centre, Double-blind, Randomized, Placebo-controlled, Clinical Trial

Urinary tract infection (UTI) is the most frequently occurring serious bacterial infection in young children and accounts 5 to 14% of emergency department visits Formation of renal scarring in children has been associated with serious complications as hypertension, preeclampsia, and end stage renal failure in young age . So, this study aims to determine whether dexamethasone reduces the renal scarring in children will be treated with antibiotics for acute pyelonephritis.

investigators propose to conduct a multi center, randomized, placebo-controlled, double-blind clinical trial, that will evaluate the efficacy of dexamethasone (0.3 mg/kg every 12 hours per day orally for 3 days) in preventing renal scarring in young febrile children (2 months to 14 years) with a first-diagnosed UTI. 120 Participants will be enrolled over a 3-year period from 6 sites.

Study Overview

• Status: Recruiting
• Conditions: Chronic Renal Failure; Urinary Tract Infections in Children; UTI; Dexamethasone; Acute Pyelonephritis; Kidney Scarring; Hypertension in Children
• Intervention / Treatment: Drug: Placebo; Drug: Dexamethasone Oral

Detailed Description

Urinary tract infection (UTI) is the most frequently occurring serious bacterial infection in young children and accounts for 5 to 14% of emergency department visits. UTIs can be divided into asymptomatic bacteriuria, cystitis, and acute pyelonephritis (APN ). The APN is associated with an increased risk of renal damage, acquired through renal scarring. Which is a consequence of the inflammatory and immune response that aim 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 scarring. One of the most relevant factors involved in formation of renal scarring is the production of inflammatory mediators (complement proteins, bactericidal peptides, cytokines , chemokines, ). hence, the use of anti-inflammatory drugs may prevent the release of these mediators and the formation of permanent renal scarring. Renal scarring in childhood has been associated with serious complications as hypertension, preeclampsia, and ESRD in young age.

Current treatment of children with UTI has focused on the treatment of vesicoureteral reflux (VUR) and on the early treatment of UTI with antibiotics. Although the presence of VUR increases the likelihood of bacteria gaining access to the kidney, correction of VUR is not sufficient to prevent scarring. Renal scarring frequently occurs in children who do not have VUR, and early diagnosis and treatment of children with VUR is not associated with a reduction in the incidence of end-stage renal disease. Similarly, early antibiotic therapy is necessary, but it is not sufficient to prevent renal scarring in most children with UTI. Because signs of UTI in children are relatively non-specific, the diagnosis is often delayed. data from many studies have shown that once the infection has localized to the renal parenchyma, treatment with antibiotics alone does not prevent scarring. hence ,It is clear that the current management is not always effective in preventing renal scarring. The proposed study aims to determine whether dexamethasone therapy - which focuses on modulation of the host inflammatory response - is effective in reducing renal scarring.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Mahmoud Alhandi Omar Helal; Phone Number: 50074001; Email: dr.mahmoud.helal@gmail.com

Study Locations

• Qatar
  • Doha, Qatar, 3050
    • Recruiting
    • Hamad Medical Corporation
    • Contact: Mahmoud Alhandi Omar Helal; Phone Number: 50074001; Email: dr.mahmoud.helal@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 10 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• First episode of acute febrile UTI.
• From 2 months to 14 years of age.
• Fever: ≥ 38.3°C, measured at home or at Pediatric Emergency centers.,

Exclusion Criteria:

• Previous history of UTI.
• Urinary tract abnormalities except VUR.
• Antibiotic use within 7 days of enrollment (except last 48 hours)
• previous renal scarring
• patients included in the study and suffered second pyelonephritis during the first 6 months
• Patients allergic to dexamethasone.
• Endocrinology diseases.
• cancer.
• Planned admission to ICU
• Other bacterial infection as meningitis or pneumonia
• Congenital/acquired immunodeficiency
• Systemic use of corticosteroids or other immunomodulation agents within 14 days of enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Drug: Placebo	Drug: Placebo; Placebo
Active Comparator: Adjuvant dexamethasone; Drug: Dexamethasone	Drug: Dexamethasone Oral; Drug: Dexamethasone 0.3mg/kg/dose twice daily for 3 days; Other Names: corticosteroids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal scarring comparatively with patients those don't take the medicine	Division of Children With Renal Scarring at the Outcome of (DMSA) Renal Scan [ Time Frame: The outcome DMSA scan will be 6 months from enrollment.] Renal scarring is defined as decreased uptake of tracer with or without loss of contours. Three radiologists independently will review all renal DMSA scans for scarring . Diagnosis of presence or absence of renal scarring for a kidney , should be endorsed by the majority of readers (2/3). The child will be determined to have renal scarring if either kidney or both kidneys have scarring by the majority of readers.	6 months

Collaborators and Investigators

• Sponsor: Hamad Medical Corporation
• Investigators: Principal Investigator: Mahmoud Alhandi Omar Helal, Hamad Medical Corporation

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2021
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: November 30, 2020
• First Posted (Actual): December 4, 2020

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Fibrosis; Renal Insufficiency, Chronic; Nephritis; Nephritis, Interstitial; Pyelitis; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Failure, Chronic; Urinary Tract Infections; Glomerulonephritis; Cicatrix; Pyelonephritis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: MRC-01-20-085

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No