J. Curtis Nickel

The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia

Background Finasteride is known to improve urinary symptoms in men with benign prostatic hyperplasia, but the extent to which the benefit is sustained and whether finasteride reduces the incidence of related events, including the need for surgery and the development of acute urinary retention, are not known. Methods In this double-blind, randomized, placebo-controlled trial, we studied 3040 men with moderate-to-severe urinary symptoms and enlarged prostate glands who were treated daily with 5 mg of finasteride or placebo for four years. Symptom scores (on a scale of 1 to 34), urinary flow rates, and the occurrence of outcome events were assessed every four months in 3016 men. Prostate volume was measured in a subgroup of the men. Complete data on outcomes were available for 2760 men. Results During the four-year study period, 152 of the 1503 men in the placebo group (10 percent) and 69 of the 1513 men in the finasteride group (5 percent) underwent surgery for benign prostatic hyperplasia (reduction in risk with finasteride, 55 percent; 95 percent confidence interval, 41 to 65 percent). Acute urinary retention developed in 99 men (7 percent) in the placebo group and 42 men (3 percent) in the finasteride group (reduction in risk with finasteride, 57 percent; 95 percent confidence interval, 40 to 69 percent). Among the men who completed the study, the mean decreases in the symptom score were 3.3 in the finasteride group and 1.3 in the placebo group (P<0.001). Treatment with finasteride also significantly improved urinary flow rates and reduced prostate volume (P<0.001). Conclusions Among men with symptoms of urinary obstruction and prostatic enlargement, treatment with finasteride for four years reduces symptoms and prostate volume, increases the urinary flow rate, and reduces the probability of surgery and acute urinary retention.

THE NATIONAL INSTITUTES OF HEALTH CHRONIC PROSTATITIS SYMPTOM INDEX: DEVELOPMENT AND VALIDATION OF A NEW OUTCOME MEASURE

AbstractPurpose: Chronic abacterial prostatitis is a syndrome characterized by pelvic pain and voiding symptoms, which is poorly defined, poorly understood, poorly treated and bothersome. Research and clinical efforts to help men with this syndrome have been hampered by the absence of a widely accepted, reliable and valid instrument to measure symptoms and quality of life impact. We developed a psychometrically valid index of symptoms and quality of life impact for men with chronic prostatitis.Materials and Methods: We conducted a structured literature review of previous work to provide a foundation for the new instrument. We then conducted a series of focus groups comprising chronic prostatitis patients at 4 centers in North America, in which we identified the most important symptoms and effects of the condition. The results were used to create an initial draft of 55 questions that were used for formal cognitive testing on chronic prostatitis patients at the same centers. After expert panel review formal...

Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia

OBJECTIVES To study the efficacy and safety of dutasteride, a dual inhibitor of the 5-alpha-reductase isoenzymes types I and II. METHODS A total of 4325 men (2951 completed) with clinical benign prostatic hyperplasia, moderate to severe symptoms (American Urological Association-Symptom Index score of 12 points or greater), a peak flow rate of 15 mL/s or less, a prostate volume of 30 cm3 or greater (as measured by transrectal ultrasonography), and a serum prostate-specific antigen level of 1.5 to 10.0 ng/mL (inclusive) were enrolled into three identical clinical trials and randomized to 0.5 mg dutasteride daily or placebo. After a 1-month, single-blind, placebo lead-in, patients were followed up for 24 months in a double-blind trial with multiple interval assessments. RESULTS At 24 months, serum dihydrotestosterone was reduced from baseline by a mean of 90.2% (median -93.7%; P <0.001), and the total prostate and transition zone volumes were reduced by a mean of 25.7% and 20.4%, respectively (P <0.001). The symptom score was improved by as early as 3 months, with pooled significance from 6 months onward (P <0.001) and a reduction of 4.5 points (21.4%) at 24 months (P <0.001). The maximal flow rate improved significantly from 1 month (P <0.01), with an increase of 2.2 mL/s reported at 24 months (P <0.001). Hence, the risk reduction of acute urinary retention was 57% and the risk reduction of benign prostatic hyperplasia-related surgical intervention was 48% compared with placebo. The drug was well tolerated. CONCLUSIONS Dutasteride is a potent inhibitor of dihydrotestosterone production that is safe and effective in terms of the reduction of prostate volume and symptoms, flow rate improvement, and the reduction of the risk of acute urinary retention and surgery during a 24-month study period.

Prevalence of prostatitis-like symptoms in a population based study using the National Institutes of Health chronic prostatitis symptom index.

PURPOSE The National Institutes of Health (NIH) chronic prostatitis symptom index was used to determine the prevalence of prostatitis-like symptoms among men (age 20 to 74 years) at risk in a community based study. MATERIALS AND METHODS The study was a cross-sectional postal survey of men age 20 to 74 years in Lennox and Addington counties, which included a large rural area, 1 major town and a suburban area with a stable population of men representative of Canadian demographics. The questionnaire collected information on 2 domains of chronic prostatitis identified in the NIH chronic prostatitis symptom index, including pain (location, severity and frequency), voiding function (irritative, obstructive), demographics, quality of life, general health and health seeking behavior. The self-reported pain score was used to identify prostatitis-like symptoms in the most discriminating domain. Based on analysis of the index final validation study comparing patients with prostatitis to normal controls and those with benign prostatic hyperplasia, the 2 questions most specific for prostatitis, including perineal and/or ejaculatory pain/discomfort, and a total pain score (0 to 21) 4 or greater were used to identify men with significant prostatitis-like symptoms. RESULTS A total of 2,987 eligible men received the survey, and it was completed by 868 (29%). Of the men 84 (9.7%) were identified as having chronic prostatitis-like symptoms (mean NIH chronic prostatitis symptom index pain score 9.1 +/- 0.3). The average age of the prostatitis population was 50 years compared with 52 years for men without prostatitis-like symptoms. Prevalence was 11.5% in men younger than 50 years and 8.5% in men 50 years or older. Of the sampled population 57 (6.6%) men had prostatitis-like symptoms and an index pain score 8 or greater (moderate to severe). The index voiding score (0 to 10) was 4.1 +/- 0.5 in men younger than 50 years compared with 1.5 +/- 0.1 for normal controls, and 4.7 +/- 0.4 in those 50 years or older compared with 1.9 +/- 0.1 for normal controls. Of the prostatitis group 60% sought medical help for their symptoms. CONCLUSIONS In our opinion this community based study using the new prostatitis symptom index confirms that chronic prostatitis-like symptoms are common.

Ciprofloxacin or Tamsulosin in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Randomized, Double-Blind Trial

Context Although the cause of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is unknown, physicians sometimes try to treat it with antibiotics or -receptor blockers. Contribution In this multicenter, double-blind factorial trial, 196 men with moderately severe CP/CPPS were randomly assigned to 6 weeks of treatment with ciprofloxacin, tamsulosin, both drugs, or placebo. Neither ciprofloxacin nor tamsulosin substantively reduced symptoms. Implications Ciprofloxacin and tamsulosin were not effective treatments for CP/CPPS. Cautions Patients had long-standing, refractory CP/CPPS and received trial treatments for only 6 weeks. Patients with new diagnoses who are given longer courses of the trial treatments might respond differently. The Editors Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder and accounts for approximately 2 million visits to physicians annually in the United States (1). The substantial impact of CP/CPPS includes bothersome lower urinary tract symptoms, sexual dysfunction, reduced quality of life (2-5), and increased health care expenditures (6). The syndrome is diagnosed only on the basis of symptoms, principally pain or discomfort in the pelvic region. No objective measures can help define the disease. Although bacteria can infect the prostate, most men with prostatitis have a negative midstream urine culture, indicating that bacteria may not be the cause of their symptoms (2). Such men are classified as having National Institutes of Health (NIH) category III prostatitis, the most common of the clinically defined prostatitis syndromes (7). It is by no means clear that the disease is characterized by inflammation of the prostate or that the prostate is responsible for symptoms in a substantial proportion of patients. Because of this uncertainty, the term CP/CPPS is used. Chronic prostatitis/chronic pelvic pain syndrome is commonly seen by primary care practitioners, internists, and urologists. In the Olmsted County Study of Urinary Symptoms and Health Status Among Men (8), a population-based study in Olmstead County, Minnesota, the overall prevalence rate of a physician-assigned diagnosis of prostatitis was 9%. Population-based surveys of symptoms have estimated that the prevalence of the syndrome ranges from 9% to 12% among men (9, 10). It is difficult to estimate the proportion of patients with symptoms lasting longer than 3 months whose disorder remains refractory to empirical therapy. These patients are commonly seen by urologists, but whether they represent a minor subpopulation of the overall symptomatic group or make up the majority of patients is unknown. We chose to study these patients because they present with a troubling, long-standing problem and are usually treated with agents of unclear benefit. Even if a relatively large number of men whose symptoms last 3 months or more are cured by standard empirical therapy and the clinical scenario we describe is uncommon, men with refractory symptoms still present a substantial problem to internists and urologists who have little information to guide therapy. Because the cause of CP/CPPS is unknown, affected men receive many empirical therapies. The 2 most common treatments prescribed by physicians are antimicrobial agents and -adrenergic receptor antagonists (2), although there is little objective evidence to support their use (11). Quinolones, such as ciprofloxacin, are commonly used to treat CP/CPPS because of their excellent penetration into the prostate and broad spectrum of coverage for uropathogens and other organisms traditionally believed to be associated with the syndrome (12). Tamsulosin, an -blocker, is an effective treatment for lower urinary tract symptoms in men with benign prostatic hyperplasia, and it has been hypothesized that tamsulosin may improve these symptoms in men with CP/CPPS. This randomized clinical trial was designed to evaluate whether ciprofloxacin or tamsulosin reduces symptoms of long-standing CP/CPPS of at least moderate severity, typical of the 488 men in our Chronic Prostatitis Cohort Study (2). The primary purpose of the trial was to test the most common prescription treatments given to men with CP/CPPS, who are commonly seen in our referral-based urologic practices. Methods Organization The Chronic Prostatitis Collaborative Research Network, a consortium sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), conducted the trial. Urologists and their clinical associates recruited patients at 10 sites in the United States and 1 site in Canada. The NIDDK established an independent data and safety monitoring board to review the progress, safety, and final analysis of the trial. The individual institutional review boards at each of the 10 participating clinical centers approved the study, and all men gave written informed consent. Participants The design of this trial has been described in detail previously (13). Participating urologists recruited both newly referred patients and patients with established CP/CPPS from their referral-based clinical practices at 10 tertiary medical centers in North America. Trial referrals came from primary care providers, internists, and other urologists. The primary diagnostic criterion was pain or discomfort in the pelvic region for at least 3 months in the previous 6 months. Severity of symptoms was assessed by using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) (14, 15). This instrument is a validated questionnaire, completed by the patient, consisting of 4 questions about pain, 3 about voiding symptoms, and 2 about quality of life. The scores in these 3 individual domains (pain, voiding, and quality of life) are combined without weighting to yield the NIH-CPSI total score. Eligible men were required to have at least moderate symptoms, defined as an NIH-CPSI score of at least 15 of 43 possible points, at the time of randomization. We excluded men who had a documented urinary tract infection (midstream urine culture > 100000 colonies/mL) within the past 3 months, a history of active genital herpes within the previous year, a history of genitourinary cancer, inflammatory bowel disease, active urethral stricture, prostate or bladder surgery, or neurologic disease affecting the bladder. We used ligase chain reaction to screen for Chlamydia in urethral urine samples and excluded men whose tests yielded positive results. Previous treatment with antimicrobial agents or -adrenergic receptor blockers, including the study drugs, had to be completed at least 4 weeks before eligibility screening. Additional details of the eligibility criteria are available elsewhere (13). Study Design and Interventions Men were randomly assigned in equal proportions within a 2 2 factorial design to receive placebo; ciprofloxacin alone, 500 mg twice daily; tamsulosin alone, 0.4 mg once daily; or a combination of both drugs (Table 1). Patients were treated for 6 weeks, at which time the primary end point was assessed. Symptoms at 9 and 12 weeks after randomization (6 weeks after completion of treatment) were also assessed to evaluate longer-term treatment response. The 2 baseline screening contacts and the primary end point contact at 6 weeks were clinic visits; interim contacts at 3, 9, and 12 weeks were conducted by telephone. Table 1. Study Design Each patient was randomly assigned by computer. A permuted block randomization schedule with varying block sizes was used, stratified by clinical site. The research pharmacist at each site provided the blinded study drugs in 2 tamper-evident bottles. All clinical investigators, research nurses, and patients were blinded to treatment assignments until all patients had completed follow-up. Outcomes The primary outcome was the change in the NIH-CPSI total score from baseline to 6 weeks. The NIH-CPSI was administered at each of the 2 baseline screening visits, 1 to 3 weeks apart, and every 3 weeks thereafter until 12 weeks. The average of the 2 scores before randomization was used as the baseline score. Evaluation of the responsiveness of the NIH-CPSI indicates that a 4-point change on a scale of 0 to 43 points represents a difference detectable by the patient. Secondary outcomes included changes in the pain, voiding, and quality-of-life subscales of the NIH-CPSI; physical and mental summary scores on the Medical Outcomes Study 12-Item Short-Form Health Survey (16); and a 7-point patient-reported global response assessment. Responders for the global response assessment were defined as men reporting that they were markedly improved or moderately improved at 6 weeks compared with baseline. Men for whom the global response assessment was missing were considered nonresponders and were included in the denominator for the assessment of response rates. Adverse events were monitored throughout the study and graded according to the National Cancer Institute Common Toxicity Criteria (ctep.cancer.gov/reporting/ctc.html). Patients were asked at each contact to report any adverse events that had occurred since the previous contact. The questions were open-ended, and researchers did not ask about any specific categories of adverse events. All events, regardless of whether they were expected reactions to the study drugs, were recorded. Attribution to treatment was also assessed. However, because it was difficult to determine whether certain adverse events, such as pain, were related to treatment or to CP/CPPS, all events were analyzed. Statistical Analysis For each of the 2 primary treatment comparisons, the recruitment goal of 184 patients provided 80% power, at a 2-sided significance level of 5%, to detect a 4-point treatment difference in the NIH-CPSI total score between baseline and 6 weeks. We recognized that although patients could detect this difference, most might not perceive it as a major improvement. However, we did not want to miss even a minor change in

LEUKOCYTE AND BACTERIAL COUNTS DO NOT CORRELATE WITH SEVERITY OF SYMPTOMS IN MEN WITH CHRONIC PROSTATITIS: THE NATIONAL INSTITUTES OF HEALTH CHRONIC PROSTATITIS COHORT STUDY

PURPOSE We examine whether leukocytes and bacteria correlate with symptom severity in men with chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS All 488 men screened into the National Institutes of Health Chronic Prostatitis Cohort Study before close of recruitment on August 22, 2001 were selected for analysis. The National Institutes of Health Chronic Prostatitis Symptom Index, including subscores, were used to measure symptoms. Urethral inflammation was defined as white blood cell (WBC) counts of 1 or more (1+) in the first voided urine. Participants were classified as category IIIa based on WBC counts of 5 or more, or 10 or more (5+, 10+) in the expressed prostatic secretion, or 1+ or 5+ either in the post-expressed prostatic secretion urine (voided urine 3) or semen. Uropathogens were classified as localizing if the designated bacterial species were absent in voided urine 1 and voided urine 2 but present in expressed prostatic secretion, voided urine 3 or semen, or present in expressed prostatic secretion, voided urine 3 or semen at 2 log concentrations higher than at voided urine 1 or 2. Associations between symptoms, and inflammation and infection were investigated using generalized Mantel-Haenszel methods. RESULTS Of all participants 50% had urethral leukocytes and of 397 with expressed prostatic secretion samples 194 (49%) and 122 (31%) had 5+ or 10+ WBCs in expressed prostatic secretion, respectively. The prevalence of category IIIa ranged from 90% to 54%, depending on the composite set of cut points. None of the index measures were statistically different (p >0.10) for selected leukocytosis subgroups. Based on prostate and semen cultures, 37 of 488 men (8%) had at least 1 localizing uropathogen. None of the index measures were statistically different (p >0.10) for selected bacterial culture subgroups. CONCLUSIONS Although men with chronic prostatitis routinely receive anti-inflammatory and antimicrobial therapy, we found that leukocytes and bacterial counts as we defined them do not correlate with severity of symptoms. These findings suggest that factors other than leukocytes and bacteria also contribute to symptoms associated with chronic pelvic pain syndrome.

Alfuzosin treatment for chronic prostatitis/chronic pelvic pain syndrome: A prospective, randomized, double-blind, placebo-controlled, pilot study

OBJECTIVES To perform a prospective, placebo-controlled study to examine the long-term efficacy of alfuzosin compared with placebo and standard therapy in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), because alpha-blockers have been suggested for the treatment of CP/CPPS. METHODS One hundred twenty consecutive men diagnosed with CP/CPPS were prospectively screened and then asked to participate in a prostatitis treatment trial. Patients who agreed to be randomized were subsequently randomized to alfuzosin 5 mg twice daily or placebo and patients who agreed to participate but not be randomized were entered into a control or standard (except alpha-blockers) therapy group. Patients were prospectively treated for 6 months and then followed up for an additional 6 months. The change from baseline in the total and domain scores of the validated Finnish version of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) was the primary outcome parameter for this study. RESULTS Seventy subjects agreed to participate in the study. The data from 66 patients were available for evaluation (17 in the alfuzosin, 20 in the placebo, and 29 in the control/standard group). At the end of 6 months of active therapy, the alfuzosin group had had a statistically significant decrease in total NIH-CPSI score compared with the placebo and control/standard groups (9.9, 3.8, and 4.3 decrease, respectively, P = 0.01). A statistically significant improvement occurred in the pain score in the alfuzosin group at 6 months compared with the placebo and control/standard groups (P = 0.01), but not in the voiding or quality-of-life score among the three groups. Of the patients in the alfuzosin group, 65% had a greater than 33% improvement in the mean NIH-CPSI total score compared with 24% and 32% of the placebo and control/standard groups, respectively (P = 0.02). At 12 months (6 months after the alfuzosin/placebo treatment was discontinued), the symptom scores in all domains of the NIH-CPSI showed deterioration compared with original baseline score in the alfuzosin and placebo groups but not in the control/standard group (NIH-CPSI score 3.5, 0.1, and 5.6 points below baseline, respectively). Gastrointestinal symptoms and a decrease in ejaculate volume were noted by 1 and 4 patients, respectively, in the alfuzosin group. No patients dropped out of the study because of an adverse event. CONCLUSIONS Six months of alfuzosin therapy for CP/CPPS is safe and well tolerated and results in a modest, but statistically significant, improvement in the NIH-CPSI, particularly in the pain domain, compared with placebo and standard/traditional treatment. The beneficial effect is only apparent after several months of treatment and disappears when treatment is discontinued.

Interstitial Cystitis/Painful Bladder Syndrome and Associated Medical Conditions With an Emphasis on Irritable Bowel Syndrome, Fibromyalgia and Chronic Fatigue Syndrome

PURPOSE We characterized and compared the impact of clinical phenotypic associations between interstitial cystitis/painful bladder syndrome and controls in relation to potentially related conditions, particularly irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome. MATERIALS AND METHODS Female patients with interstitial cystitis/painful bladder syndrome and controls with no interstitial cystitis/painful bladder syndrome completed a biopsychosocial phenotyping questionnaire battery which included demographics/history form, self-reported history of associated conditions, and 10 validated questionnaires focused on symptoms, suffering/coping and behavioral/social factors. RESULTS Questionnaires were completed by 205 patients with interstitial cystitis/painful bladder syndrome and 117 controls matched for age. Prevalence of self-reported associated condition diagnosis in interstitial cystitis/painful bladder syndrome vs controls was irritable bowel syndrome 38.6% vs 5.2%, fibromyalgia 17.7% vs 2.6% and chronic fatigue syndrome 9.5% vs 1.7% (all p <0.001). In the interstitial cystitis/painful bladder syndrome cohort 50.3% reported no other associated condition, 24.4% had interstitial cystitis/painful bladder syndrome + irritable bowel syndrome only, 2.5% had interstitial cystitis/painful bladder syndrome + fibromyalgia only, 1.5% had interstitial cystitis/painful bladder syndrome + chronic fatigue syndrome only, while 20.2% had multiple associated conditions. As the number of associated conditions increased (ie localized, regional, systemic), pain, stress, depression and sleep disturbance increased while social support, sexual functioning and quality of life deteriorated. Anxiety and catastrophizing remained increased in all groups. Symptom duration was associated with this apparent phenotypic progression. CONCLUSIONS Irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome are more prevalent in patients with interstitial cystitis/painful bladder syndrome than in asymptomatic control subjects, and result in significant impact. There are at least 3 distinct clinical phenotypes based on identification of overlapping syndrome patterns. A suggestion that remains to be proven with longitudinal studies is that there may be progression over time from an organ centric to a regional and finally to a systemic pain syndrome with progression of symptom severity, and deterioration of cognitive and psychosocial parameters.

Management of Chronic Prostatitis/ Chronic Pelvic Pain Syndrome: A Systematic Review and Network Meta-analysis

CONTEXT Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is common, but trial evidence is conflicting and therapeutic options are controversial. OBJECTIVE To conduct a systematic review and network meta-analysis comparing mean symptom scores and treatment response among α-blockers, antibiotics, anti-inflammatory drugs, other active drugs (phytotherapy, glycosaminoglycans, finasteride, and neuromodulators), and placebo. DATA SOURCES We searched MEDLINE from 1949 and EMBASE from 1974 to November 16, 2010, using the PubMed and Ovid search engines. STUDY SELECTION Randomized controlled trials comparing drug treatments in CP/CPPS patients. DATA EXTRACTION Two reviewers independently extracted mean symptom scores, quality-of-life measures, and response to treatment between treatment groups. Standardized mean difference and random-effects methods were applied for pooling continuous and dichotomous outcomes, respectively. A longitudinal mixed regression model was used for network meta-analysis to indirectly compare treatment effects. DATA SYNTHESIS Twenty-three of 262 studies identified were eligible. Compared with placebo, α-blockers were associated with significant improvement in symptoms with standardized mean differences in total symptom, pain, voiding, and quality-of-life scores of -1.7 (95% confidence interval [CI], -2.8 to -0.6), -1.1 (95% CI, -1.8 to -0.3), -1.4 (95% CI, -2.3 to -0.5), and -1.0 (95% CI, -1.8 to -0.2), respectively. Patients receiving α-blockers or anti-inflammatory medications had a higher chance of favorable response compared with placebo, with pooled RRs of 1.6 (95% CI, 1.1-2.3) and 1.8 (95% CI, 1.2-2.6), respectively. Contour-enhanced funnel plots suggested the presence of publication bias for smaller studies of α-blocker therapies. The network meta-analysis suggested benefits of antibiotics in decreasing total symptom scores (-9.8; 95% CI, -15.1 to -4.6), pain scores (-4.4; 95% CI, -7.0 to -1.9), voiding scores (-2.8; 95% CI, -4.1 to -1.6), and quality-of-life scores (-1.9; 95% CI, -3.6 to -0.2) compared with placebo. Combining α-blockers and antibiotics yielded the greatest benefits compared with placebo, with corresponding decreases of -13.8 (95% CI, -17.5 to -10.2) for total symptom scores, -5.7 (95% CI, -7.8 to -3.6) for pain scores, -3.7 (95% CI, -5.2 to -2.1) for voiding, and -2.8 (95% CI, -4.7 to -0.9) for quality-of-life scores. CONCLUSIONS α-Blockers, antibiotics, and combinations of these therapies appear to achieve the greatest improvement in clinical symptom scores compared with placebo. Anti-inflammatory therapies have a lesser but measurable benefit on selected outcomes. However, beneficial effects of α-blockers may be overestimated because of publication bias.

Levofloxacin for chronic prostatitis/chronic pelvic pain syndrome in men: a randomized placebo-controlled multicenter trial.

OBJECTIVES To perform a Canadian multicenter randomized placebo-controlled trial to evaluate the safety and efficacy of 6 weeks of levofloxacin therapy compared with placebo in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Uncontrolled studies have supported the use of antibiotics in CP/CPPS. METHODS Men with a National Institutes of Health (NIH) diagnosis of CP/CPPS (specifically, no infection localized to the prostate) were randomized to levofloxacin (500 mg/day) or placebo for 6 weeks in 11 Canadian centers. Patients were assessed at baseline and at 3, 6, and 12 weeks with the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and global patient assessments (subjective global assessment and patient assessment questionnaire). RESULTS Eighty men (average age 56.0 years, range 36 to 78; duration of symptoms 6.5 years, range 0.6 to 32) were randomized to receive levofloxacin (n = 45) or placebo (n = 35). All were evaluated in an intent-to-treat analysis. Both groups experienced progressive improvement in symptoms as measured by the NIH-CPSI. However, the difference in response was not statistically or clinically significant at end of treatment (6 weeks) or at the end of the follow-up visits (12 weeks). No patients withdrew because of adverse events. One patient withdrew before the 6-week assessment. Adverse events (all mild) were reported in 20% of the levofloxacin group and 17% of the placebo group. CONCLUSIONS This pilot placebo-controlled study showed that 6 weeks of levofloxacin therapy in men diagnosed with CP/CPPS resulted in symptom improvement that was not significantly different from that with placebo at end of treatment or follow-up. The clinical ramifications of these findings need to be addressed.