STRATA: Safe Testing of Risk for AsymptomaTic MicrohematuriA

Use of a Multiplexed Molecular Biomarker Test Cxbladder, in Real World Decision Making to Provide Clinical Utility Using a Randomized Design ("STRATA Study")

To evaluate the clinical utility associated with the integration of Cxbladder into the evaluation of subjects presenting with hematuria for evaluation of urothelial carcinoma (UC) without compromising detection of UC.

Study Overview

• Status: Active, not recruiting
• Conditions: Urothelial Carcinoma; Hematuria
• Intervention / Treatment: Diagnostic test: Cxbladder

Detailed Description

Randomised two arm pragmatic clinical study to be conducted at multiple sites in US and Canada. The trial will recruit hematuria subjects, presenting to qualified sites (academic, community), who are being evaluated for urothelial carcinoma (UC). Up to 100 consecutive eligible subjects will be recruited per site.

• Study Type: Interventional
• Enrollment (Actual): 554
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yair Lotan, MD; Phone Number: 2146458764; Email: yair.lotan@utsouthwestern.edu

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z1M9
      • The prostate centre- Diamond Health care centre
  • Ontario
    • London, Ontario, Canada, N6A5W9
      • London Health Sciences Centre Victoria Hospital
• United States
  • California
    • Los Angeles, California, United States, 90089
      • Institute of Urology, USC Norris Comprehensive Cancer Center
  • Florida
    • Winter Garden, Florida, United States, 34787
      • Avant Concierge Urology
  • Illinois
    • Chicago, Illinois, United States, 60515
      • Accellacare
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407-3799
      • Allina Health Cancer Institute
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota, Department of Urology
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Division of urology, Penn State Milton S Hershey Medical Center
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Department of Urology,Vanderbilt University
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • San Antonio, Texas, United States, 78229
      • UTHSA - Mays Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient is undergoing investigation of recent confirmed hematuria, as defined by the AUA/SUFU Guideline (Barocas DA, Boorjian SA, Alvarez RD et al. Microhematuria: AUA/SUFU guideline, J Urol 2020; 204:778) (by either flexible or rigid cystoscopy/TURBT), including hematuria subjects referred due to suspicious/positive imaging, in order to determine the presence of urothelial carcinoma.
• Able to provide a voided urine sample of the required minimum volume
• Able to give written consent
• Able and willing to comply with study requirements
• Aged 18 years or older

Exclusion Criteria

• Prior history of bladder malignancy or pelvic radiotherapy. Prior history prostate or renal cell carcinoma within the last 5 years.
• Prior genitourinary manipulation (flexible or rigid cystoscopy / catheterisation, urethral dilation) in the 14 days before urine collection,
• Known current pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Test, subjects categorised as "low risk" or "Not low risk"; A clinical risk factor nomogram risk classification will be used in this study. The nomogram categorizes subjects as either "low risk" or "not low risk" categories. "Low risk" subjects satisfy all conditions and "not low risk" satisfies at least one of the conditions.The Cxbladder Triage test result will be provided to physicians for all "low risk" subjects on the test arm. If a "low risk" subject has a Cxbladder Triage negative test result then the indication is to rule out the subject without further assessment. The decision to rule-out or further evaluate is solely that of the physician and subject. If the "low risk" subjects are not Cxbladder Triage negative then a Cxbladder Detect test result will also be provided. The indication is further evaluation as per standard of care. Subjects categorised as "not low risk" will be evaluated as per standard of care. Note that Cxbladder test results will be available for eventual analysis for these subjects.	Diagnostic test: Cxbladder; The Cxbladder Triage test result will be provided to physicians for all "low risk" subjects on the test arm. If a "low risk" subject has a Cxbladder Triage negative test result then the indication is to rule out the subject without further assessment. The decision to rule-out or further evaluate is solely that of the physician and subject. If the "low risk" subjects are not Cxbladder Triage negative then a Cxbladder Detect test result will also be provided. The indication is further evaluation as per standard of care. "Not low risk" patients will be evaluated as per standard of care.
No Intervention: Control; Subjects on the control arm will be on standard of care. Trial nomogram clinical risk factor categorization for control arm subjects will not be provided to the physician (but appropriate information will be collected on the CRF to enable sub-group analysis) No Cxbladder test results will be provided for control arm subjects. Note that Cxbladder test results will be available for eventual analysis for these subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure the change in cystoscopy procedure use count between control and test arms when Cxbladder Triage is used in the evaluation	To evaluate the increase in utility as defined by the reduction in cystoscopy procedure count when Cxbladder is used in the evaluation. The comparison will be made when comparing test and control arms on a per subject basis. The gold standard for determination of a confirmed clinical diagnosis is cystoscopy confirmed by pathology, plus imaging or any follow-up investigations relating to the visit.	The outcome measure will be assessed by 6 months after trial completion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure the change in total procedure use (and the invasive procedure sub-group) count between control and test arms when Cxbladder is used in the evaluation.	To evaluate the increase in utility as defined by the reduction in total procedures (and the invasive procedures subgroup) count when Cxbladder is used in the evaluation. The comparison will be made when comparing test and control arms on a per subject basis.	The outcome measure will be assessed by 6 months after trial completion.
To measure the number of subjects who were incorrectly diagnosed associated with the integration of Cxbladder into the evaluation of subjects (or sub-cohorts on test and control arms) presenting with hematuria for evaluation of UC	To quantify the false negative rate (the percentage of the negative fraction incorrectly diagnosed) associated with the integration of Cxbladder into the evaluation of subjects (or sub-cohorts on test and control arms) presenting with hematuria for evaluation of UC	The outcome measure will be assessed by 6 months after trial completion.
To clinically validate the performance characteristics and test negative rate of the Cxbladder Detect+ test.	The Cxbladder Detect+ test results will be compared to that of cystoscopy, which is the gold standard method for diagnosing urothelial cancer; the true positive and true negative rates will be measured, along with the false positive and false negative rates of the test. The results will be reported as sensitivity, specificity, positive and negative predictive value and test negative rate of the Cxbladder Detect+ test for detecting urothelial cancer in patients referred for evaluation of hematuria.	The outcome measure will be assessed by 6 months after trial completion.
Quantify performance characteristics of Cxbladder signatures including for the detection of high grade/stage UC.	The Cxbladder signature test results will be compared to that of cystoscopy, which is the gold standard method for diagnosing urothelial cancer; the true positive and true negative rates will be measured, along with the false positive and false negative rates of the test. The results will be reported as sensitivity, specificity, positive and negative predictive value of the Cxbladder signature tests for detecting urothelial cancer in patients referred for evaluation of hematuria.	The outcome measure will be assessed by 6 months after trial completion.

Collaborators and Investigators

• Sponsor: Pacific Edge Limited
• Investigators: Study Chair: Tony Lough, PhD, Pacific Edge Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2019
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: April 24, 2019
• First Submitted That Met QC Criteria: June 12, 2019
• First Posted (Actual): June 17, 2019

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 7, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Hemorrhage; Urination Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hematuria
• Other Study ID Numbers: CXB/2019/US

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