Prostatitis
Conditions
Keywords
Prostatitis, Non-bacterial Prostatitis, Prostatodynia, Alfuzosin, Alpha-adrenergic blocker
Brief summary
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
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.
Interventions
DRUGAlfuzosin
DRUGPlacebo
Sponsors
University of Pennsylvania
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Decline in Total Score ≥4 for the NIH-CPSI Total Score From Baseline to 12 Weeks | Baseline and 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Subscales of the NIH-CPSI | Baseline and12 weeks | 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. |
| Change in Subscales of the McGill Pain Questionnaire | Baseline and 12 weeks | 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. |
| Change in Medical Outcomes Study Short Form 12 | Baseline and 12 weeks | 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. |
| Global Response Assessment (GRA) | 12 weeks | 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). |
| Change in International Index of Erectile Dysfunction (IIEF) | Baseline and 12 weeks | For the International Index of Erectile Function, higher scores indicate better sexual function; range, 0 to 75. |
| Change in Male Sexual Health Questionnaire | Baseline and 12 weeks | 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. |
| Change in Hospital Anxiety and Depression Scale | Baseline and 12 weeks | For the Hospital Anxiety and Depression Scale, higher scores indicate greater anxiety and depression; range, 0 to 42. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alfuzosin 10 mg of alfuzosin once daily for 12 weeks | 138 |
| Placebo 10 mg of an identical-looking placebo once daily for 12 weeks | 134 |
| Total | 272 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 |
| Overall Study | Dissatisfied/No longer interested | 6 | 6 |
| Overall Study | Lost to Follow-up | 8 | 7 |
| Overall Study | Personal constraints/Other | 5 | 0 |
Baseline characteristics
| Characteristic | Total | Alfuzosin | Placebo |
|---|---|---|---|
| Age, Continuous | 40.1 years STANDARD_DEVIATION 11.8 | 40.1 years STANDARD_DEVIATION 11.4 | 40.1 years STANDARD_DEVIATION 12.3 |
| Hospital Anxiety and Depression Scale | 12.8 units on a scale STANDARD_DEVIATION 7.4 | 12.8 units on a scale STANDARD_DEVIATION 7.6 | 12.8 units on a scale STANDARD_DEVIATION 7.1 |
| International Index of Erectile Function | 53.2 units on a scale STANDARD_DEVIATION 17.7 | 53.5 units on a scale STANDARD_DEVIATION 17.9 | 52.8 units on a scale STANDARD_DEVIATION 17.4 |
| Likert Pain and Urgency Scale Average pain score | 5.0 units on the scale STANDARD_DEVIATION 2 | 4.9 units on the scale STANDARD_DEVIATION 2 | 5.0 units on the scale STANDARD_DEVIATION 1.9 |
| Likert Pain and Urgency Scale Urgency score | 4.6 units on the scale STANDARD_DEVIATION 2.6 | 4.4 units on the scale STANDARD_DEVIATION 2.6 | 4.7 units on the scale STANDARD_DEVIATION 2.6 |
| Male Sexual Health Questionnaire | 30.2 units on a scale STANDARD_DEVIATION 7 | 30.0 units on a scale STANDARD_DEVIATION 7.4 | 30.4 units on a scale STANDARD_DEVIATION 6.6 |
| McGill Pain Questionnaire Affective score | 2.6 units on a scale STANDARD_DEVIATION 3.3 | 2.6 units on a scale STANDARD_DEVIATION 3.3 | 2.6 units on a scale STANDARD_DEVIATION 3.2 |
| McGill Pain Questionnaire Sensory score | 8.8 units on a scale STANDARD_DEVIATION 6.1 | 8.6 units on a scale STANDARD_DEVIATION 5.9 | 8.9 units on a scale STANDARD_DEVIATION 6.2 |
| McGill Pain Questionnaire Total score | 11.4 units on a scale STANDARD_DEVIATION 8.7 | 11.2 units on a scale STANDARD_DEVIATION 8.6 | 11.6 units on a scale STANDARD_DEVIATION 8.7 |
| NIH-CPSI Pain score | 11.3 units on a scale STANDARD_DEVIATION 3.4 | 11.1 units on a scale STANDARD_DEVIATION 3.3 | 11.5 units on a scale STANDARD_DEVIATION 3.4 |
| NIH-CPSI Quality of life score | 4.6 units on a scale STANDARD_DEVIATION 1 | 4.5 units on a scale STANDARD_DEVIATION 1.1 | 4.7 units on a scale STANDARD_DEVIATION 0.9 |
| NIH-CPSI Total score | 24.5 units on a scale STANDARD_DEVIATION 6.1 | 23.8 units on a scale STANDARD_DEVIATION 6.3 | 25.1 units on a scale STANDARD_DEVIATION 5.9 |
| NIH-CPSI Urinary score | 4.7 units on a scale STANDARD_DEVIATION 2.9 | 4.5 units on a scale STANDARD_DEVIATION 2.8 | 4.9 units on a scale STANDARD_DEVIATION 2.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 27 Participants | 13 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 36 Participants | 20 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 24 Participants | 17 Participants | 7 Participants |
| Race (NIH/OMB) White | 185 Participants | 88 Participants | 97 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 272 Participants | 138 Participants | 134 Participants |
| SF-12 Mental component summary | 44.5 units on a scale STANDARD_DEVIATION 10.6 | 44.0 units on a scale STANDARD_DEVIATION 10.9 | 44.9 units on a scale STANDARD_DEVIATION 10.2 |
| SF-12 Physical component summary | 45.6 units on a scale STANDARD_DEVIATION 9 | 45.5 units on a scale STANDARD_DEVIATION 9.6 | 45.6 units on a scale STANDARD_DEVIATION 8.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 138 | 0 / 134 |
| other Total, other adverse events | 40 / 138 | 46 / 134 |
| serious Total, serious adverse events | 1 / 138 | 2 / 134 |
Outcome results
Primary
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
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Alfuzosin | Number of Participants With Decline in Total Score ≥4 for the NIH-CPSI Total Score From Baseline to 12 Weeks | 68 Participants |
| Placebo | Number of Participants With Decline in Total Score ≥4 for the NIH-CPSI Total Score From Baseline to 12 Weeks | 66 Participants |
Comparison: Sample-size calculations were based on a 2-sided alpha of 0.05 with 80% power to detect a difference of 20 between response rates (40% placebo and 60% alfuzosin) for the Fisher's exact test. We calculated that a total sample of 270 participants would be required (135 per study group). This proposed sample size included a 20% increase to adjust for clustering within clinical sites and a 5% increase for interim monitoring.p-value: 0.9995% CI: [-11.2, 11]Mantel Haenszel
Secondary
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.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alfuzosin | Change in Hospital Anxiety and Depression Scale | -2.6 units on a scale | Standard Deviation 5.7 |
| Placebo | Change in Hospital Anxiety and Depression Scale | -1.5 units on a scale | Standard Deviation 5.5 |
p-value: 0.0895% CI: [-2.4, 0.2]t-test, 2 sided
Secondary
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.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alfuzosin | Change in International Index of Erectile Dysfunction (IIEF) | 0.5 units on a scale | Standard Deviation 12.7 |
| Placebo | Change in International Index of Erectile Dysfunction (IIEF) | -0.2 units on a scale | Standard Deviation 14.7 |
p-value: 0.9495% CI: [-2.6, 4]t-test, 2 sided
Secondary
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.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alfuzosin | Change in Male Sexual Health Questionnaire | 1.7 units on a scale | Standard Deviation 4.5 |
| Placebo | Change in Male Sexual Health Questionnaire | 0.6 units on a scale | Standard Deviation 6.8 |
p-value: 0.0695% CI: [-0.3, 2.5]t-test, 2 sided
Secondary
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.
Time frame: Baseline and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alfuzosin | Change in Medical Outcomes Study Short Form 12 | Physical component | 3.0 units on a scale | Standard Deviation 7.4 |
| Alfuzosin | Change in Medical Outcomes Study Short Form 12 | Mental component | 4.0 units on a scale | Standard Deviation 10.5 |
| Placebo | Change in Medical Outcomes Study Short Form 12 | Physical component | 3.5 units on a scale | Standard Deviation 8.1 |
| Placebo | Change in Medical Outcomes Study Short Form 12 | Mental component | 1.9 units on a scale | Standard Deviation 10.6 |
Comparison: Physical component summary (0-100) change in scoresp-value: 0.695% CI: [-2.3, 1.3]t-test, 2 sided
Comparison: Mental component summary (0-100) Absolute Difference between Groups (95% CI)p-value: 0.1695% CI: [-0.4, 4.6]t-test, 2 sided
Secondary
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.
Time frame: Baseline and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alfuzosin | Change in Subscales of the McGill Pain Questionnaire | Total score | -3.4 units on a scale | Standard Deviation 6.4 |
| Alfuzosin | Change in Subscales of the McGill Pain Questionnaire | Sensory score | -2.5 units on a scale | Standard Deviation 5 |
| Alfuzosin | Change in Subscales of the McGill Pain Questionnaire | Affective score | -1.0 units on a scale | Standard Deviation 2.1 |
| Placebo | Change in Subscales of the McGill Pain Questionnaire | Total score | -3.1 units on a scale | Standard Deviation 6.5 |
| Placebo | Change in Subscales of the McGill Pain Questionnaire | Sensory score | -2.3 units on a scale | Standard Deviation 4.9 |
| Placebo | Change in Subscales of the McGill Pain Questionnaire | Affective score | -0.9 units on a scale | Standard Deviation 2.3 |
Comparison: McGill Total Scorep-value: 0.4595% CI: [-1.8, 1.2]t-test, 2 sided
Comparison: McGill Sensory Scorep-value: 0.4795% CI: [-1.4, 1]t-test, 2 sided
Comparison: McGill Affective Scorep-value: 0.8995% CI: [-0.6, 0.4]t-test, 2 sided
Secondary
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.
Time frame: Baseline and12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alfuzosin | Change in Subscales of the NIH-CPSI | Total score | -7.1 units on a scale | Standard Deviation 9 |
| Alfuzosin | Change in Subscales of the NIH-CPSI | Pain score | -3.3 units on a scale | Standard Deviation 4.5 |
| Alfuzosin | Change in Subscales of the NIH-CPSI | Urinary score | -1.2 units on a scale | Standard Deviation 2.6 |
| Alfuzosin | Change in Subscales of the NIH-CPSI | Quality-of-life score | -1.2 units on a scale | Standard Deviation 1.5 |
| Placebo | Change in Subscales of the NIH-CPSI | Quality-of-life score | -1.2 units on a scale | Standard Deviation 1.5 |
| Placebo | Change in Subscales of the NIH-CPSI | Total score | -6.5 units on a scale | Standard Deviation 8.5 |
| Placebo | Change in Subscales of the NIH-CPSI | Urinary score | -1.0 units on a scale | Standard Deviation 2.6 |
| Placebo | Change in Subscales of the NIH-CPSI | Pain score | -3.0 units on a scale | Standard Deviation 4.4 |
Comparison: Total score (0-43) change from baselinep-value: 0.795% CI: [-2.7, 1.5]t-test, 2 sided
Comparison: Pain score (0-21) change from baselinep-value: 0.6495% CI: [-1.4, 0.8]t-test, 2 sided
Comparison: Urinary score (0-10) change from baselinep-value: 0.6295% CI: [-0.8, 0.4]t-test, 2 sided
Comparison: Quality of life score (0-12) change from baselinep-value: 0.9995% CI: [-0.4, 0.4]t-test, 2 sided
Secondary
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).
Time frame: 12 weeks
Population: The analysis population for this outcome is larger than the number of participants who completed the trial because a few participant answered this question without completing the other questionnaires
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Alfuzosin | Global Response Assessment (GRA) | Slight improvement | 26 Participants |
| Alfuzosin | Global Response Assessment (GRA) | Moderate worsening | 2 Participants |
| Alfuzosin | Global Response Assessment (GRA) | No change | 36 Participants |
| Alfuzosin | Global Response Assessment (GRA) | Moderate improvement | 25 Participants |
| Alfuzosin | Global Response Assessment (GRA) | Slight worsening | 6 Participants |
| Alfuzosin | Global Response Assessment (GRA) | Marked worsening | 1 Participants |
| Alfuzosin | Global Response Assessment (GRA) | Marked improvement | 23 Participants |
| Placebo | Global Response Assessment (GRA) | Marked worsening | 1 Participants |
| Placebo | Global Response Assessment (GRA) | Moderate worsening | 4 Participants |
| Placebo | Global Response Assessment (GRA) | Marked improvement | 16 Participants |
| Placebo | Global Response Assessment (GRA) | Moderate improvement | 29 Participants |
| Placebo | Global Response Assessment (GRA) | Slight improvement | 32 Participants |
| Placebo | Global Response Assessment (GRA) | No change | 36 Participants |
| Placebo | Global Response Assessment (GRA) | Slight worsening | 5 Participants |
Comparison: Marked or moderate improvement at 12 weeks Absolute Difference in Rates % (95% CI)p-value: 0.995% CI: [-9, 2.5]Mantel Haenszel