Benign Prostatic Hyperplasia (BPH) Screening Tool Case Finding Study in Subjects >=50 Years

Implementation of a Screening Tool for Subjects With Benign Prostatic Enlargement/Obstruction to Identify Men >=50 Years Presenting in General Practice With Other Co-morbidities Who Should be Assessed for BPH

This non-randomized, interventional study will be conducted in a general practice setting to assess the utility of a benign prostatic enlargement (BPE)/benign prostatic obstruction (BPO) screening tool in conjunction with prostate specific antigen (PSA) in finding men confirmed to have BPH on full urologist assessment of diagnostic test results. The tool may help a General Practitioners (GP) to identify subjects who may have BPH for further tests and improve the speed of referrals to specialists when this is appropriate. The utility of the screening tool will be compared to the validated tool in wide clinical use, the International Prostate Symptom Score (IPSS). This study does not have any formal hypothesis in terms of the primary and secondary endpoint proportions. A BPE/BPO screening tool identifies lower urinary tract symptoms (LUTS) probably due to BPH in men not yet presenting with LUTS. The results of this screening tool will be used for further investigation. All subjects testing positive on the BPE/BPO screening tool (score >=3) tool or on the IPSS (score >=8) will be enrolled and offered a PSA test and urinalysis to establish a diagnosis of probable BPH (Part I-Visit 1). The GP may perform a digital rectal examination (DRE) which will be repeated by the urologist to confirm the diagnosis and to rule out an abnormality suggesting prostate cancer. The GP will make a diagnosis of probable BPH based upon screening results and lab tests which suggest that they are related to BPH and not other causes of such symptoms. The GP will phone the subject to report yes or no for probable BPH Part II (Visit 2). If the subject has probable BPH, the GP will schedule the subject for Visit 3 with an urologist. If the subject does not have probable BPH, then it will be considered that the subject has completed the study. Subjects that proceed to Part II (Visit 3) will be scheduled for a urology assessment performed by an urologist. This assessment includes a DRE and a brief physical exam and review of the PSA test, for a confirmatory diagnosis of BPH and estimation of risk of progression of BPH. Approximately 1,500 subjects presenting to a GP for reasons unrelated to this study will be screened for probable BPH to yield 500 subjects being referred to an urologist. The duration of the study will be 1 week (+/- 4 days) and up to 6 weeks to allow for GP and urologist visit scheduling.

Study Overview

• Status: Completed
• Conditions: Prostatic Hyperplasia
• Intervention / Treatment: Other: Benign prostatic enlargement (BPE)/Benign prostatic obstruction (BPO) screening tool; Other: International Prostate Symptom Score (IPSS) screening tool

• Study Type: Interventional
• Enrollment (Actual): 1679
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Aigrefeuille Sur Maine, France, 44140
    • GSK Investigational Site
  • Grenay, France, 62160
    • GSK Investigational Site
  • Haute Goulaine, France, 44115
    • GSK Investigational Site
  • La Montagne, France, 44620
    • GSK Investigational Site
  • Nantes cedex 2, France, 44277
    • GSK Investigational Site
  • Rosiers-d'Egletons, France, 19300
    • GSK Investigational Site
  • Rouen, France, 76000
    • GSK Investigational Site
  • Thouars, France, 79100
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 10117
    • GSK Investigational Site
  • Magdeburg, Germany, 39120
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Weinheim, Baden-Wuerttemberg, Germany, 69469
      • GSK Investigational Site
  • Bayern
    • Muenchen, Bayern, Germany, 80339
      • GSK Investigational Site
  • Hessen
    • Floersheim, Hessen, Germany, 65439
      • GSK Investigational Site
  • Niedersachsen
    • Buchholz, Niedersachsen, Germany, 21244
      • GSK Investigational Site
  • Sachsen
    • Dippoldiswalde, Sachsen, Germany, 01744
      • GSK Investigational Site
    • Freital, Sachsen, Germany, 01705
      • GSK Investigational Site
    • Leipzig, Sachsen, Germany, 04329
      • GSK Investigational Site
• Italy
  • Puglia
    • Aradeo, Puglia, Italy, 73040
      • GSK Investigational Site
    • Cutrofiano (LE), Puglia, Italy, 73020
      • GSK Investigational Site
    • Galatina (LE), Puglia, Italy, 73013
      • GSK Investigational Site
    • Ruffano (LE), Puglia, Italy, 73049
      • GSK Investigational Site
  • Toscana
    • Civitella Paganico (GR), Toscana, Italy, 58045
      • GSK Investigational Site
    • Grosseto, Toscana, Italy, 58100
      • GSK Investigational Site
• Russian Federation
  • Arkhangelsk, Russian Federation, 163020
    • GSK Investigational Site
  • Ivanovo, Russian Federation, 153005
    • GSK Investigational Site
  • Izhevsk, Russian Federation, 426063
    • GSK Investigational Site
  • Moscow, Russian Federation, 123098
    • GSK Investigational Site
  • Naro-Fominsk, Russian Federation, 143300
    • GSK Investigational Site
  • Novosibirsk, Russian Federation, 630099
    • GSK Investigational Site
  • Odintsovo, Russian Federation, 143005
    • GSK Investigational Site
  • Saint Petersburg, Russian Federation, 195067
    • GSK Investigational Site
  • Saint Petesburg, Russian Federation, 195030
    • GSK Investigational Site
  • Saint-Petersburg, Russian Federation, 198328
    • GSK Investigational Site
  • Saint-Petersburg, Russian Federation, 195271
    • GSK Investigational Site
  • Smolensk, Russian Federation, 214031
    • GSK Investigational Site
  • St'Petersburg, Russian Federation, 197706
    • GSK Investigational Site
  • Tomsk, Russian Federation, 634 050
    • GSK Investigational Site
  • Ulyanovsk, Russian Federation, 432063
    • GSK Investigational Site
  • Yaroslavl, Russian Federation, 150000
    • GSK Investigational Site
• Spain
  • Bormujo (Sevilla), Spain, 41930
    • GSK Investigational Site
  • Cadiz, Spain, 11009
    • GSK Investigational Site
  • Granada, Spain, 18014
    • GSK Investigational Site
  • Sevilla, Spain, 41014
    • GSK Investigational Site
  • Valencia, Spain, 46026
    • GSK Investigational Site
  • Valencia, Spain, 46010
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Greater than or equal to (>=) 50 years of age at the time of signing the informed consent form.
• Male.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and protocol.
• Present in a General Practice setting for a reason unrelated to this study.
• Positive IPSS score >=8 and/or positive BPE/BPO screening tool score >=3.

Exclusion Criteria:

• History of BPH for which they have received test procedures, medical intervention and/or medicine.
• History of prostate-related LUTS for which they have received test procedures, medical intervention and/or medicine.
• History of prostatic surgery (including transurethral resection of the prostate (TURP), balloon dilatation, thermotherapy, and/or stent replacement) or other invasive or minimally invasive procedures to treat BPH.
• Has other conditions that may cause urinary symptoms (e.g., neurogenic bladder, bladder neck contracture, urethral stricture, bladder malignancy, acute or chronic prostatitis, or acute or chronic urinary tract infections, etc.).
• History or evidence of prostate cancer (e.g., positive biopsy or ultrasound, suspicious DRE and/or rising PSA).
• Current or prior use of the following: 5alpha-reductase inhibitors (finasteride or dutasteride); anti-cholinergics (e.g. oxybutynin, propantheline, tolterodine, solifenacin, darifenacin, mirabegron) alpha-adrenoreceptor blockers (i.e., indoramin, prazosin, terazosin, tamsulosin, alfuzosin, doxazosin and silodosin), herbal products for urinary symptoms; Use of any investigational study drug within 30 days or 5 half-lives of the drug in question, (whichever is longer), preceding the first study visit.
• Use within previous 30 days at Visit 1 of: phosphodiesterase type 5 inhibitor (PDE-5) inhibitors for erectile dysfunction; anabolic steroids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: BPE/BPO screening and IPSS screening tool; Subjects presenting to a GP with a primary complaint other than LUTS will be screened for probable BPH using BPE/BPO screening tool and the IPSS screening tool. Subjects testing positive on the BPE/BPO screening tool or on the IPSS will be enrolled and offered a prostate specific antigen (PSA) test and urinalysis to establish a diagnosis of probable benign prostatic hyperplasia (BPH) (Part I - Visit 1). If the GP determines that the subject has probable BPH (IPSS >=8 and/or BPE/BPO questionnaire >=3 with a PSA >=2 ng per ml), the subject will proceed to Part II and will be scheduled for an urologist assessment and diagnostic tests to confirm or refute a BPH diagnosis and to assess risk of progression of BPH.

Other: Benign prostatic enlargement (BPE)/Benign prostatic obstruction (BPO) screening tool; The BPE/BPO screening tool has been developed using the currently recommended Food and Drug Administration (FDA) 2009 guidelines for developing patient-completed questionnaires such as Patient Reported Outcomes. The tool to be used in this study in the General Practice setting has undergone validation in a urology setting to demonstrate the validity of the tool in populations with and without a definite diagnosis of BPH. Subjects who have a positive score on the BPE/BPO screening tool (total score >=3) and meet all other eligibility requirements will be enrolled in Part I of the study.; Other: International Prostate Symptom Score (IPSS) screening tool; The International Prostate Symptom Score (IPSS) score is a validated tool to assess the severity of LUTS symptoms, and has similarly been used for assessing symptomatic efficacy of treatments for BPH. Subjects who have a positive score on the IPSS tool (score >=8) and meet all other eligibility requirements will be enrolled in Part I of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Men With Confirmed Diagnosis of BPH	Confirmed diagnosis of BPH was based on full urologist diagnostic testing with a positive result on the BPE/BPO screening tool (score >=3) and serum PSA >=2 ng/mL. The BPE/BPO questionnaire consists of three questions each with a score ranging from 0= never experienced to 5= almost always experienced. Participants with probable BPH underwent full urologist diagnostic testing, which included review of medical history, symptoms and previous tests, brief physical examination, Digital rectal examination (DRE). Proportion of participants was calculated by dividing number of participants with a positive result on the BPE/BPO screening tool (Score >= 3) and a diagnosis of BPH by the urologist (Numerator) by number of participants with a positive result on the BPE/BPO screening tool (Score >= 3) and a BPH assessment by the urologist (Denominator). 95% confidence interval on the proportion was calculated by using the exact (Clopper-Pearson) method.	Up to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Men That Are Confirmed to Have BPH Based on Full Urologist Assessment of Diagnostic Test Results Among Men With a Positive Result on the IPSS, BPE/BPO and IPSS, and BPE/BPO or IPSS Screening Tools and Serum PSA >=2 ng/mL	Confirmed diagnosis of BPH was based on full urologist diagnostic testing with a positive result on the IPSS, BPE/BPO and IPSS, BPE/BPO or IPSS screening tools and serum PSA >=2 ng/mL. The BPE/BPO questionnaire consists of three questions each with a score ranging from 0= never experienced to 5= almost always experienced. IPSS tool is used to assess the severity of LUTS symptoms with a score ranging from 0= never experienced to 5= almost always experienced. Participants with probable BPH underwent full urologist diagnostic testing, which included review of medical history, symptoms and previous tests, brief physical examination, DRE. Proportion of participants was calculated by dividing number of participants with a positive result on the screening tool and a diagnosis of BPH by the urologist (Numerator) by number of participants with a positive result on the screening tool and a BPH assessment by the urologist(Denominator).	Up to 6 weeks
Number of Men That Are Confirmed to be at Risk for BPH Progression Based Upon Full Urologist Assessment Among Men With a Positive Result on the BPE/BPO, IPSS, BPE/BPO and IPSS, and BPE/BPO or IPSS Screening Tools and Serum PSA >=2 ng/mL	Confirmed risk for BPH was based on full urologist diagnostic testing with a positive result on the BPE/BPO and/or IPSS screening tool and probable GP BPH diagnosis. The BPE/BPO questionnaire consists of 3 questions each with a score from 0= never experienced to 5= almost always experienced. IPSS tool is used to assess the severity of LUTS symptoms with a score from 0= never experienced to 5= almost always experienced. Participants with probable BPH underwent full urologist diagnostic testing, which included review of medical history, symptoms and previous tests, physical examination, DRE. Participants with PSA >=2.0 ng/mL and other tests were considered as at risk for BPH. Proportion of participants was calculated by dividing number of participants with a positive result on the screening tool and diagnosis of BPH progression risk (Numerator) by number of participants with a positive result on the screening tool and a BPH progression risk assessment by the urologist (Denominator).	Up to 6 weeks
Number of Men That Are Diagnosed With Probable BPH as Assessed by the GP Among Men With a Positive Result on the BPE/BPO, IPSS, BPE/BPO and IPSS, and BPE/BPO or IPSS Screening Tools	Diagnosis of probable BPH was based on GP assessment among men with a positive result on the BPE/BPO and/or IPSS screening tool. The BPE/BPO questionnaire consists of 3 questions each with a score from 0= never experienced to 5= almost always experienced. IPSS tool is used to assess the severity of LUTS symptoms with a score from 0= never experienced to 5= almost always experienced. Probable BPH is the presumptive diagnosis of urinary tract obstruction from an enlarged prostate based on clinical symptoms and findings where urinary symptoms are not apparently related to any other cause. Participants underwent GP assessment and lab result review by GP. Participants with PSA >=2 ng/mL were assessed for probable BPH. Proportion of participants was calculated by dividing number of participants with a positive result on the screening tool and diagnosis of probable BPH (Numerator) by number of participants with a positive result on the screening tool and a BPH assessment by GP (Denominator).	Up to 6 weeks
Summary of Agreement Between BPE/BPO and IPSS Screening Tools	Agreement between the IPSS and BPE/BPO tools had to utilize the screened population, as the evaluable population did not include any participants with IPSS <8 and BPE/BPO<3. All screened participants with IPSS and BPE/BPO results were utilized (2327 of the 2343 participants had IPSS and BPE/PO results). There were 16 participants (2343 minus 2327) in the screened population without IPSS and BPE/BPO results, and hence were not included in the calculation of the Kappa statistic. Kappa statistic values of <0 were characterized as no agreement, 0 to 0.20 as slight, 0.21 to 0.40 as fair, 0.41 to 0.60 as moderate, 0.61 to 0.80 as substantial, and 0.81 to 1.00 as almost perfect agreement. The 95% confidence interval for the Kappa statistic is based on the asymptotic standard error.	Day 1

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Tubaro A, Niero M, Adalig B, Lulic Z, Plastino J, Kimbrough C, Manyak MJ. Evaluation of a 3-item screening tool to identify men with benign prostatic enlargement/obstruction in a primary care cohort. Minerva Urol Nephrol. 2022 Feb;74(1):85-92. doi: 10.23736/S2724-6051.20.03834-5. Epub 2020 Sep 29.

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2016
• Primary Completion (Actual): February 27, 2017
• Study Completion (Actual): February 27, 2017

Study Registration Dates

• First Submitted: April 28, 2016
• First Submitted That Met QC Criteria: April 28, 2016
• First Posted (Estimate): May 2, 2016

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 10, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: IPSS; Lower urinary tract symptoms; LUTS; BPH; Benign prostatic hyperplasia; BPO; Screening tool; International Prostate Symptom Score; BPE; Benign prostatic enlargement; Benign prostatic obstruction
• Additional Relevant MeSH Terms: Pathologic Processes; Prostatic Diseases; Prostatic Hyperplasia; Hyperplasia
• Other Study ID Numbers: 116114

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study is available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)