Trial to Compare Alfuzosin Versus Placebo in the Treatment of Chronic Prostatitis/Chronic Pelvic Pain Syndrome

A Randomized Clinical Trial to Evaluate the Efficacy and Safety of 10mg Alfuzosin in the Treatment of Chronic Prostatitis / Chronic Pelvic Pain Syndrome (CP/CPPS) in Recently-Diagnosed and/or Newly-Symptomatic Alpha-blocker Naïve Patients

The purpose of this randomized clinical trial is to evaluate the efficacy and safety of the alpha adrenergic blocker Alfuzosin (Uroxatral) in men with relatively new onset of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Alfuzosin is a once daily (10 mg capsule), FDA approved medication for an indication in benign prostatic hyperplasia (BPH). The effectiveness of alfuzosin in improving lower urinary tract symptoms in patients with BPH has been documented in a number of placebo-controlled studies. A number of small studies have also suggested that alfuzosin ameliorates CP/CPPS symptoms through a similar alpha-blockade mechanism. This study will enable further testing of this hypothesis

Study Overview

• Status: Completed
• Conditions: Prostatitis
• Intervention / Treatment: Drug: Placebo; Drug: Alfuzosin

Detailed Description

The two primary objectives of this study are:

• To compare 12 weeks of treatment with alfuzosin versus placebo in newly-diagnosed, alpha-blocker naive CP/CPPS participants with respect to the primary endpoint in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI).
• To evaluate the safety and tolerability of 12 weeks of alfuzosin in newly-diagnosed, alpha-blocker naïve CP/CPPS participants.

The proportion of "responders" in each treatment arm will be compared to evaluate the overall safety and efficacy of alfuzosin as compared to placebo. Approximately 270 eligible patients, 135 per treatment arm, will be randomized and followed for a period of twelve (12) weeks after randomization.

There will be four research-clinic visits during which data for the primary and secondary outcome measures will be collected: visit 1 involves screening, visit 2 involves collection of baseline data and randomization, visit 3 is the 6-week evaluation, and visit 4 is the 12-week evaluation of the primary end point.

• Study Type: Interventional
• Enrollment (Actual): 272
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 3N6
      • Queen's University
• United States
  • California
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine at UCLA
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern U. Feinberg School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Harvard Medical School- Massachusetts General Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
  • Washington
    • Seattle, Washington, United States, 98108
      • University of Washington- Harborview Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participant has signed and dated the appropriate Informed Consent document.
• Participant is male.
• Participant is at least 18 years of age.
• Participant has had symptoms of discomfort or pain in the pelvic region for at least a six-week interval at the time of presentation.
• Symptoms bothersome enough to prompt a physician visit have been present for two years or less.

Exclusion Criteria:

• Participant has evidence of facultative Gram negative or enterococcus with a value of greater than or equal to 1000 colony forming units (CFU) /ml in mid-stream urine (VB2).
• Participant has previously received alfuzosin (Uroxatral®), tamsulosin hydrochloride (Flomax®), doxazosin mesylate (Cardura®), terazosin hydrochloride (HCL) (Hytrin®), or other alpha-adrenergic receptor blockers for symptoms of CP/CPPS or within the past two years for any other reason.
• Participant has a history of prostate, penile, testicular, bladder, or urethral cancer or has undergone pelvic radiation, systemic chemotherapy, or intravesical chemotherapy.
• Participant has a history of moderate or severe hepatic impairment, severe renal sufficiency, severe or unstable cardiovascular (i.e. prolonged QT), respiratory, hematological, endocrinological, neurological or other somatic disorders.
• Participant has unilateral orchialgia without pelvic symptoms, active urethral stricture, or neurological disease or disorder affecting the bladder.
• Participant has uninvestigated, significant hematuria.
• Participant has undergone transurethral prostatectomy (TURP), transurethral incision of the prostate (TUIP), transurethral Incision or Resection of the Bladder Neck (TUIBN), transurethral microwave thermotherapy (TUMT), transurethral needle ablation (TUNA), balloon dilation of the prostate, open prostatectomy or any other prostate surgery or treatment such as cryotherapy or thermal therapy.
• Participant has a neurological impairment or psychiatric disorder preventing his understanding of consent and his ability to comply with the protocol.
• Participant is currently taking exclusionary medications such as potent CYP3A4 inhibitors (i.e. ketoconazole, itraconazole, or ritonavir) or erythromycin.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alfuzosin; 10 mg of alfuzosin once daily for 12 weeks	Drug: Alfuzosin
Placebo Comparator: Placebo; 10 mg of an identical-looking placebo once daily for 12 weeks	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Decline in Total Score ≥4 for the NIH-CPSI Total Score From Baseline to 12 Weeks	For the National Institutes of Health Chronic Prostatitis Symptom Index (NIHCPSI) total score, higher scores indicate more severe symptoms and scores range from 0 to 43. The primary outcome was a decline of at least 4 from baseline to 12 weeks	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Response Assessment (GRA)	The response rate for the global response assessment was based on marked or moderate improvement at 12 weeks using a 7 point scale (marked worsening, moderate worsening, no change, slight improvement, moderate improvement, marked improvement).	12 weeks
Change in Subscales of the NIH-CPSI	For the National Institutes of Health Chronic Prostatitis Symptom Index (NIHCPSI), higher scores indicate more severe symptoms (for the quality-of-life score, higher scores indicate a more negative effect). Score ranges are as follows: total score, 0 to 43; pain score, 0 to 21; urinary score, 0 to 10, quality-of-life score, 0 to 12; and average pain and urgency scores, 0 to 10.	Baseline and12 weeks
Change in Subscales of the McGill Pain Questionnaire	For the McGill Pain Questionnaire, higher scores indicate greater pain. Score ranges are as follows: total score, 0 to 45; sensory score, 0 to 33; affective score, 0 to 12.	Baseline and 12 weeks
Change in Medical Outcomes Study Short Form 12	For the Medical Outcomes Study Short Form Health Survey 12 (SF-12), higher scores indicate better quality of life. Score range for both the physical and mental component summaries is 0 to 100.	Baseline and 12 weeks
Change in Hospital Anxiety and Depression Scale	For the Hospital Anxiety and Depression Scale, higher scores indicate greater anxiety and depression; range, 0 to 42.	Baseline and 12 weeks
Change in International Index of Erectile Dysfunction (IIEF)	For the International Index of Erectile Function, higher scores indicate better sexual function; range, 0 to 75.	Baseline and 12 weeks
Change in Male Sexual Health Questionnaire	For the Male Sexual Health Questionnaire, higher scores indicate better function with respect to erection and ejaculation and greater satisfaction with sexual life; range, 0 to 40.	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: University of Pennsylvania
• Investigators: Study Director: John Kusek, PhD, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Study Director: Leroy Nyberg, MD PhD, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

General Publications

• Propert KJ, Alexander RB, Nickel JC, Kusek JW, Litwin MS, Landis JR, Nyberg LM, Schaeffer AJ; Chronic Prostatitis Collaborative Research Network. Design of a multicenter randomized clinical trial for chronic prostatitis/chronic pelvic pain syndrome. Urology. 2002 Jun;59(6):870-6. doi: 10.1016/s0090-4295(02)01601-1.
• Alexander RB, Propert KJ, Schaeffer AJ, Landis JR, Nickel JC, O'Leary MP, Pontari MA, McNaughton-Collins M, Shoskes DA, Comiter CV, Datta NS, Fowler JE Jr, Nadler RB, Zeitlin SI, Knauss JS, Wang Y, Kusek JW, Nyberg LM Jr, Litwin MS; Chronic Prostatitis Collaborative Research Network. Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial. Ann Intern Med. 2004 Oct 19;141(8):581-9. doi: 10.7326/0003-4819-141-8-200410190-00005.
• Litwin MS. A review of the development and validation of the National Institutes of Health Chronic Prostatitis Symptom Index. Urology. 2002 Dec;60(6 Suppl):14-8; discussion 18-9. doi: 10.1016/s0090-4295(02)02296-3.
• Schaeffer AJ; National Institute of Diabetes and Digestive and Kidney Diseases of the US National Institutes of Health. NIDDK-sponsored chronic prostatitis collaborative research network (CPCRN) 5-year data and treatment guidelines for bacterial prostatitis. Int J Antimicrob Agents. 2004 Sep;24 Suppl 1:S49-52. doi: 10.1016/j.ijantimicag.2004.02.009.
• Schaeffer AJ, Landis JR, Knauss JS, Propert KJ, Alexander RB, Litwin MS, Nickel JC, O'Leary MP, Nadler RB, Pontari MA, Shoskes DA, Zeitlin SI, Fowler JE Jr, Mazurick CA, Kishel L, Kusek JW, Nyberg LM; Chronic Prostatitis Collaborative Research Network Group. Demographic and clinical characteristics of men with chronic prostatitis: the national institutes of health chronic prostatitis cohort study. J Urol. 2002 Aug;168(2):593-8.
• Schaeffer AJ, Datta NS, Fowler JE Jr, Krieger JN, Litwin MS, Nadler RB, Nickel JC, Pontari MA, Shoskes DA, Zeitlin SI, Hart C; Chronic Prostatitis Collaborative Research Network. Overview summary statement. Diagnosis and management of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Urology. 2002 Dec;60(6 Suppl):1-4. doi: 10.1016/s0090-4295(02)01979-9.
• Nickel JC, Krieger JN, McNaughton-Collins M, Anderson RU, Pontari M, Shoskes DA, Litwin MS, Alexander RB, White PC, Berger R, Nadler R, O'Leary M, Liong ML, Zeitlin S, Chuai S, Landis JR, Kusek JW, Nyberg LM, Schaeffer AJ; Chronic Prostatitis Collaborative Research Network. Alfuzosin and symptoms of chronic prostatitis-chronic pelvic pain syndrome. N Engl J Med. 2008 Dec 18;359(25):2663-73. doi: 10.1056/NEJMoa0803240.

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: February 7, 2005
• First Submitted That Met QC Criteria: February 7, 2005
• First Posted (Estimate): February 8, 2005

Study Record Updates

• Last Update Posted (Actual): June 12, 2020
• Last Update Submitted That Met QC Criteria: May 27, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Alfuzosin; Prostatitis; Non-bacterial Prostatitis; Prostatodynia; Alpha-adrenergic blocker
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Prostatic Diseases; Pelvic Pain; Prostatitis; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Alfuzosin
• Other Study ID Numbers: CPCRN2 Afluzosin; U01DK065209 (NIH); RFA-DK-03-004 (Other Grant/Funding Number: NIDDK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/cpcrn2-rct1/?query=CPCRN

Drug and device information, study documents

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