Topical Steroids to Prevent Recurrent Urinary Tract Infections in Uncircumcised Male Infants: a Pilot Study

Official title

Topical Steroids to Prevent Recurrent Urinary Tract Infections in Uncircumcised Male Infants With a First Febrile Urinary Tract Infection: a Multi-center Pilot Study

Overview

The goal of this smaller clinical trial is to evaluate the study design of this research to help prepare for a larger research study in the future. The future larger study would focus on whether steroid cream can reduce recurrent urinary tract infections in male infants, who are not circumcised. Male infants, who are enrolled in this study, would receive either the steroid cream or a placebo cream (a look alike cream without steroids). The cream would be applied twice a week for four weeks. Then there would be two follow up visits with the research team to measure whether the infant experienced any urinary tract infections and to measure parent perceptions of their experience participating in the study.

Detailed description

This is a multi-center pilot study involving recruitment of uncircumcised male infants \< 6 months of age from outpatient clinics, emergency department and inpatient settings in Houston, Texas. Additionally, the pilot study will involve recruitment of hospitalized infants from Seattle Children's Hospital in Seattle, Washington.

Various strategies for screening and recruitment will be piloted across settings to identify the most effective processes for the future study. Hospitalized infants would be enrolled prior to discharge. Children recruited from the clinic or emergency department would be enrolled in the Texas Children's Hospital Clinical Research Center. Randomization would occur after enrollment and would be conducted by the investigational pharmacy. The research investigators will teach the legal guardians of the infants how to apply the cream.

The first follow up visit would occur after completion of the cream treatment and would be 28-38 days after being enrolled or after hospital discharge, whichever came later. The last follow up visit would occur 6-7 months after being enrolled or hospital discharge.

Interventions

• Drug betamethasone valerate 0.1% cream
  Steroid cream applied to the foreskin and glans twice a day for four weeks.
• Drug Placebo cream
  Placebo cream is applied to the foreskin and glans twice a day for four weeks.

Primary outcome measures

• Feasibility of recruitment across different settings [Time frame: up to 2 weeks]

Secondary outcome measures (12)

• Rate of recurrent urinary tract infection [Time frame: Between 14 days of completing antibiotics for the first urinary tract infection and through the last follow up visit, which occurs 6 months after randomization.]
• Total number of recurrent urinary tract infections [Time frame: 6 month follow up period]
• Number of subsequent hospitalizations for recurrent urinary tract infections [Time frame: 6 month follow up period]
• Number of subsequent emergency department visits for recurrent urinary tract infection [Time frame: Within 6 month follow up period]
• Rate of provider diagnosed recurrent urinary tract infection [Time frame: 6 month follow up period]
• Number of Lumbar punctures [Time frame: 6 month follow up period]
• Self reported Rate of Referral for Circumcision [Time frame: During the 6 month follow up period]
• Self Reported Adherence to Applying Topical Cream Regimen [Time frame: Measured at 4 week follow up visit]
• Rate of Adverse effects of cream [Time frame: At 4 weeks]
• Number of infants with Congenital anomalies of the kidney and urinary tract [Time frame: From time of enrollment through last follow up visits 6 months later]
• Number of subsequent clinic visits for recurrent urinary tract infection [Time frame: During the 6 month follow up period]
• Attrition rate [Time frame: Through the 6 month follow up period for each participant]

Eligibility criteria

Inclusion criteria

• Uncircumcised male infants < 6 months old
• Both physician and laboratory confirmed diagnosis of first UTI
• Fever (temperature ≥38.0 C) or hypothermia (temperature <36.0 C) per ED/hospitalization or parental report

Exclusion criteria

• Legal guardian not available to provide informed consent
• Infant in Child Protective Services (CPS) custody
• Legal guardian would like Urology referral for circumcision
• Circumcision is medically indicated due to recurrent episodes of balanitis or ballooning of foreskin during urination
• Past diagnosis of penile abnormalities (diagnoses of epispadius, hypospadias or congenital penile curvature (chordee))
• Prior use of topical steroid therapy for phimosis
• History of hypersensitivity to topical steroids
• Legal guardian is not fluent in English OR Spanish
• Foreskin assessed to be fully retractable
• Open wounds present on penis or in groin region

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 3 centers

• Texas Children's Hospital Main campus — Houston
• Texas Children's Hospital West Campus — Katy
• Seattle Children's Hospital — Seattle

Publications

• Lee JW, Cho SJ, Park EA, Lee SJ. Topical hydrocortisone and physiotherapy for nonretractile physiologic phimosis in infants. Pediatr Nephrol. 2006 Aug;21(8):1127-30. doi: 10.1007/s00467-006-0104-8. Epub 2006 Jun 22. PMID 16791612
• Chen CJ, Satyanarayan A, Schlomer BJ. The use of steroid cream for physiologic phimosis in male infants with a history of UTI and normal renal ultrasound is associated with decreased risk of recurrent UTI. J Pediatr Urol. 2019 Oct;15(5):472.e1-472.e6. doi: 10.1016/j.jpurol.2019.06.018. Epub 2019 Jun 25. PMID 31345734
• Moreno G, Ramirez C, Corbalan J, Penaloza B, Morel Marambio M, Pantoja T. Topical corticosteroids for treating phimosis in boys. Cochrane Database Syst Rev. 2024 Jan 25;1(1):CD008973. doi: 10.1002/14651858.CD008973.pub3. PMID 38269441
• Dave S, Afshar K, Braga LH, Anderson P. Canadian Urological Association guideline on the care of the normal foreskin and neonatal circumcision in Canadian infants (full version). Can Urol Assoc J. 2018 Feb;12(2):E76-E99. doi: 10.5489/cuaj.5033. Epub 2017 Dec 1. No abstract available. PMID 29381458
• Conway PH, Cnaan A, Zaoutis T, Henry BV, Grundmeier RW, Keren R. Recurrent urinary tract infections in children: risk factors and association with prophylactic antimicrobials. JAMA. 2007 Jul 11;298(2):179-86. doi: 10.1001/jama.298.2.179. PMID 17622599
• Khan A, Jhaveri R, Seed PC, Arshad M. Update on Associated Risk Factors, Diagnosis, and Management of Recurrent Urinary Tract Infections in Children. J Pediatric Infect Dis Soc. 2019 May 11;8(2):152-159. doi: 10.1093/jpids/piy065. PMID 30053044
• Shaikh N, Morone NE, Bost JE, Farrell MH. Prevalence of urinary tract infection in childhood: a meta-analysis. Pediatr Infect Dis J. 2008 Apr;27(4):302-8. doi: 10.1097/INF.0b013e31815e4122. PMID 18316994

Identifiers

NCT: NCT07508124 · H-57427

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗