Clinical trial NCT06996301: Clinical Validity and Utility of PCR Compared to Conventional Culture and Sensitivity Testing for the Management of Complicated Urinary Tract Infections in Adults
Official title: Clinical Utility of a PCR Test for the Management of Complicated Urinary Tract Infections in Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Urinary Tract Infection Complicated
Urinary Tract Infection (cUTI)
Urinary Tract Infection (Diagnosis)
Keywords: Complicated urinary tract infection (cUTI)
Polymerase Chain Reaction (PCR) diagnostic
Urine culture and sensitivity (C&amp;S) testing
Favorable Clinical Outcomes (FCl)
Turnaround Time
Randomized Controlled Trial (RCT)
Treatment Outcome
Lead sponsor: Doc Lab Inc
Sponsor class: INDUSTRY
Collaborators: name: Dicentra Inc.
First posted: 2025-05-30
Enrollment: 773
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Managing complicated urinary tract infections (cUTIs) poses significant challenges, often resulting in the over-prescription of empiric antibiotics. This approach exposes patients to multiple antimicrobials and raises the risk of inadequate treatment efficacy. The purpose of this study is to assess and compare the clinical utility of molecular testing (PCR) versus conventional culture and sensitivity (C\&S) in managing cUTI, to identify optimal management strategies for cUTI patients.

This was a multi-center (6 sites in the united states), randomized, parallel, investigator-blinded, clinical trial to assess the clinical utility of PCR by comparing the diagnostic and therapeutic outcomes of PCR diagnostic methods to those of conventional C\&S in managing cUTIs in adults. All patients who met all the inclusion criteria and non of the exclusion criteria and signed an informed consent form were enrolled and randomized to one of two testing protocols used to guide treatment (PCR guided Arm, and C\&S guided Arm). Patients were randomized in a 1:1 ratio based on their unique sequential randomization numbers assigned at enrollment.

Urine samples were collected from all patients and tested using both PCR and C\&S methods before randomization; however, investigators remained blinded to the comparator test results throughout the trial. To ensure unbiased treatment decisions, clinicians were blinded to the comparator test results. Treatment was prescribed solely based on the assigned test-PCR results for the PCR arm and C\&S results for the C\&S arm. The comparator test results remained blinded until the end of the study (EOS)

Urine specimens were collected using a clean-catch midstream technique at two distinct time points-at baseline visit/before randomization (Day1) and at EOS visit (Day 28)-following targeted therapy based on the assigned diagnostic arm. Collected samples were immediately stored at 2-8 ◦C until analysis to preserve sample integrity. Upon receipt, urine samples were aliquoted for parallel testing, with one portion analyzed using PCR (QuantStudio 7 or 12 and KingFisher) and the other processed using C\&S methodologies.

Molecular testing (Doc Lab UTM 2.0) involved qualitative PCR amplification targeting 28 uropathogen species and 16 classes of antibiotic resistance genes, covering both bacterial and fungal pathogens. All urine samples for urine C\&S were shipped to the central laboratory. The urine culture, isolation of uropathogen(s), initial identification of pathogen(s), and bacterial counts in urine were conducted in the central laboratory. The urine samples were cultured and quantified using a calibrated loop to identify a quantitative count of bacteria at a lower limit of 10\^5 CFU/mL. All purified pathogen(s) were further analyzed for species identification and antimicrobial sensitivity

The primary endpoint was the number (and percentage) of subjects in each study arm with favorable clinical outcomes (FCl) at the EOS visit. The FCl was defined as a patient's clinical response, assessed by the treating investigator, indicating either clinical improvement or cure. Clinical improvement was defined as the resolution of at least one symptom of cUTI present at baseline, absence of new cUTI symptoms, and/or avoidance of parenteral antibiotic therapy following randomization. Clinical cure was defined as the complete resolution of all acute signs and symptoms of cUTI present at baseline, to the extent that no further antimicrobial therapy (either IV or oral) was required for the treatment of the cUTI.

The secondary endpoint included several assessments:

* Number (and percentage) of subjects with microbiological eradication at the EOS, defined as achieving a quantitative urine culture at the EOS indicating a reduction of all uro-pathogens present at baseline to \<10\^5 colony forming unit per milliliter (CFU/mL) and the absence of baseline pathogens detected by EOS urine PCR (Cq \> 33);
* Subjective measurement of treating investigator satisfaction score through a questionnaire at EOS, evaluated factors such as the ease of interpreting the test result, its availability, and its usefulness in clinical decision-making and patient management compared to the comparator;
* Comparison of turnaround time between molecular diagnostic procedures and conventional diagnostic
* Overall agreeability between the diagnostic results generated by PCR versus C\&S as assessed by discordant analysis
* Assessment of the favorable clinical outcome of patients with discordant results \[PCR(+), CS(-) and PCR(-), CS(+)\]


Eligibility criteria: Inclusion Criteria: Subjects must meet all of the following criteria to be considered eligible for admission to the study:

I1. At least 18 years of age at the time of consent; I2. Presenting at least two of the following new, persistent or worsening cUTI signs and symptoms at screening visit: a) fever (temperature \>38 degrees Celsius or \>100.4 degrees Fahrenheit), hypothermia (temperature \<35.5 degrees Celsius or \<95.9 degrees Fahrenheit), rigors, or chills b) dysuria, urinary frequency, urgency, or hematuria c) suprapubic pain or pelvic pain d) costovertebral angle (CVA) tenderness e) nausea or vomiting f) radiographic evidence of pyelonephritis g) leukocytosis I3. Urine specimen with evidence of pyuria a) dipstick analysis positive for nitrite and/or leukocyte esterase, or; b) ≥10 white blood cells (WBCs) per cubic millimeter \[mm3\], or; c) ≥10 WBCs per high power field (hpf), or; d) clinically suspected pyuria (e.g. change in urine color, sediment in urine, or foul-smelling urine) I4. Having cUTI that requires microbiological diagnosis and treatment as suspected by the Investigator; I5. Presenting active UTI that failed to resolve on first-line therapy or identified as a high-risk\* patient population; \*High-risk patient population include those who are elderly (≥65years), male, pregnant, having recurrent UTI (≥3/year), with underlying co-morbidities (e.g. diabetes, immunosuppression, or CKD), or with known functional and anatomical abnormalities of the urinary tract (e.g. stones, stents, recent instrumentation, indwelling catheters, neurogenic bladder, or PKD) I6. Able to provide at least 8 mL urine at visit 1 and 3; I7. Willing to abstain from sexual intercourse or use condoms during any sexual contact until the End-of-Study (EOS) visit is complete; I8. Willing to comply with protocol requirements, including availability for follow-up for the duration of the study

Exclusion Criteria: Subjects meeting any of the following criteria will not be eligible for admission to the study:

E1. Unable or unwilling to provide written informed consent; E2. Unable to read and write in English (surveys are not available or validated in any other language than English); E3. Currently participating in or has participated in an interventional clinical trial with an investigational product or device within 30 days prior to the Screening Visit; E4. Currently on or chronic use of any antibiotics for any clinical indication, other than UTI (refer to section 6.3.); E5. Receipt of any dose of a potentially therapeutic oral or systemic antibiotics for the treatment of UTI within 48 hours before the study baseline urine is obtained E6. Pregnant women with known fetal congenital anomaly (e.g., genetic abnormality or major congenital malformation) based on antenatal ultrasound; E7. Any rapidly progressing disease or immediately life-threatening illness, including acute hepatic failure, or respiratory failure E8. Medical condition or other factor that in the judgment of the investigator might affect ability to comply with procedures.

Primary outcomes:
measure: Favorable clinical outcomes (FCl)
timeFrame: at End Of Study (EOS) visit (Day 28)
Secondary outcomes:
measure: Microbiological Eradication
timeFrame: at End Of Study (EOS) visit (Day 28)
measure: Treating investigator satisfaction score
timeFrame: at End Of Study (EOS) visit (Day 28)
measure: Turnaround time
timeFrame: at Baseline (Day 1) and at End Of Study (EOS) visit (Day 28)
measure: Overall agreeability
timeFrame: at Baseline (Day 1) and at End Of Study (EOS) visit (Day 28)
measure: Discordant results analysis
timeFrame: at End Of Study (EOS) visit (Day 28)
Other outcomes:
Locations:
city: San Jose
country: United States
facility: Silicon Valley Medical Development
state: California
city: Albany
country: United States
facility: Albany Urology Clinic & Surgery Center
state: Georgia
city: Evans
country: United States
facility: Augusta Urology Associates
state: Georgia
city: Moultrie
country: United States
facility: Colquitt Regional Medical Center
state: Georgia
city: St Joseph
country: United States
facility: Phoenix Urology of St Joseph
state: Missouri
city: Norman
country: United States
facility: Norman Urology Associates
state: Oklahoma
Study officials:
affiliation: Doc Lab Inc
name: Roel Chavez
role: STUDY_CHAIR
affiliation: MED-US Consulting, LLC
name: Thomas K Huard, PhD
role: PRINCIPAL_INVESTIGATOR
References: