Pentosan polysulfate sodium for treatment of interstitial cystitis/bladder pain syndrome: insights from a randomized, double-blind, placebo controlled study.

PURPOSE: We compared the efficacy and safety of the currently recommended dose of pentosan polysulfate sodium with a third of the daily dose and with placebo. MATERIALS AND METHODS: In this multicenter, double-blind, randomized, placebo controlled study 368 adults with interstitial cystitis/bladder pain syndrome, defined as an ICSI total score of 8 or greater and a score of greater than 0 on the 4 ICSI component items, received pentosan polysulfate sodium 100 mg once daily or 3 times daily, or matching placebo for 24 weeks. Study eligibility was not based on cystoscopy findings. ICSI was administered at baseline, and at weeks 4, 8, 12, 18 and 24. Unblinded interim analysis performed at 6 years with 54% of the target number of 645 patients enrolled resulted in early study termination. RESULTS: There was no statistically significant difference between the pentosan polysulfate sodium group and the placebo group or between the 2 pentosan polysulfate sodium groups for the primary end point, defined as responder achieving a 30% or greater reduction from the baseline ICSI total score at study end. This primary end point was achieved by 48 of 118 patients (40.7%) in the placebo group, and by 51 of 128 (39.8%) and 52 of 122 (42.6%) in the pentosan polysulfate sodium 100 mg once daily and 3 times daily groups, respectively. Pentosan polysulfate sodium was well tolerated with a similar percent of patients (range 10.2% to 13.3%) across the groups discontinuing due to an adverse event. CONCLUSIONS: Results of this study in a broad population of patients with symptoms consistent with interstitial cystitis revealed no treatment effect vs placebo for pentosan polysulfate sodium at the currently established dose or at a third of the daily dose.

Cyclosporine A for refractory interstitial cystitis/bladder pain syndrome: experience of 3 tertiary centers.

PURPOSE: Cyclosporine A is a fifth-tier treatment option in the American Urological Association guidelines for interstitial cystitis/bladder pain syndrome. It was more effective than pentosanpolysulfate in a Finnish trial, but experience elsewhere is limited. Some centers use cyclosporine A off label for carefully selected patients but the number of patients in each center is small. We performed a retrospective review combining data from 3 tertiary centers that focus on interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS: Charts were reviewed for patients with interstitial cystitis/bladder pain syndrome who received cyclosporine A. Response was defined as markedly improved on the 7-point global response assessment (2 centers) or as at least a 50% decrease in Interstitial Cystitis Symptom Index score (1 center). RESULTS: The study included 14 men and 30 women. Mean patient age was 55.5 years (range 27 to 75) and mean followup was 20.8 months (range 3 to 81). A total of 34 patients had Hunner lesions. Of these patients 29 (85%) responded but 6 eventually stopped cyclosporine A for adverse events, resulting in a success rate of 68% (23 of 34) for patients with Hunner lesions. In contrast, only 3 of 10 patients without Hunner lesions responded (30%). For all responders, the response occurred within 4 months. CONCLUSIONS: Cyclosporine A had a high success rate for patients with Hunner lesions in whom more conservative options, including endoscopic treatment, had failed. The success rate was low for patients without Hunner lesions. A 3 to 4-month trial is sufficient time to assess response. Adverse events were common and led to discontinuation of cyclosporine A for some patients. Close monitoring is needed, especially for blood pressure and renal function.

AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome.

PURPOSE: To provide a clinical framework for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS: A systematic review of the literature using the MEDLINE® database (search dates 1/1/83-7/22/09) was conducted to identify peer reviewed publications relevant to the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. Insufficient evidence-based data were retrieved regarding diagnosis and, therefore, this portion of the Guideline is based on Clinical Principles and Expert Opinion statements. The review yielded an evidence base of 86 treatment articles after application of inclusion/exclusion criteria. These publications were used to create the majority of the treatment portion of the Guideline. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate) or C (low). Additional treatment information is provided as Clinical Principles and Expert Opinion when insufficient evidence existed. See text and algorithm for definitions, and detailed diagnostic management, and treatment frameworks. RESULTS: The evidence-based guideline statements are provided for diagnosis and overall management of interstitial cystitis/bladder pain syndrome as well as for various treatments. The panel identified first through sixth line treatments as well as developed guideline statements on treatments that should not be offered. CONCLUSIONS: Interstitial cystitis/bladder pain syndrome is best identified and managed through use of a logical algorithm such as is presented in this Guideline. In the algorithm the panel identifies an overall management strategy for the interstitial cystitis/bladder pain syndrome patient. Diagnosis and treatment methodologies can be expected to change as the evidence base grows in the future.

Clinical practice guidelines to inform evidence-based clinical practice.

BACKGROUND: With the volume of medical research currently published, any one practitioner cannot independently review the literature to determine best evidence-based medical care. Additionally, non-specialists usually do not have the experience to know best practice for all of the frequent clinical circumstances for which there is no good evidence. Clinical practice guidelines (CPGs) help clinicians to address these problems because they are systematically created documents that summarize knowledge and provide guidance to assist in delivering high-quality medicine. They aim to improve health care by identifying evidence that supports the best clinical care and making clear which practices appear to be ineffective. METHODS: Non-structured literature review. RESULTS: CPGs combine evidence-based medicine (on topics for which evidence exists) with expert opinion (on topics for which there is no evidence). The optimal CPG applies structured and transparent judgments, from an unbiased and diverse panel which includes both clinical experts and non-physicians, to a systematic evidence review. It includes decisions in areas in which clinical data are both available and unavailable. The resulting guideline statements should be clearly linked to the quality of the available evidence and the target patient(s) should be clearly defined, so that the reader can assess strength and applicability of the statements to an individual patient. CONCLUSIONS: The application of high-quality CPGs improves patient care, but all too often CPGs are not used to the greatest advantage because of inadequate dissemination and incorporation into practice. This article provides an overview of CPGs, focusing on their justification, creation, improvement, and use.

Breaking the cycle of pain in interstitial cystitis/painful bladder syndrome: toward standardization of early diagnosis and treatment: consensus panel recommendations.

Chronic pelvic pain (CPP) affects about 15% of female adults in the United States. The source of this pain in many women is the bladder, specifically interstitial cystitis/painful bladder syndrome (IC/PBS). Despite the frequent occurrence of IC/PBS as a cause of CPP, there currently are no universally accepted guidelines for diagnosis and treatment of this disorder, and, consequently, many patients do not receive appropriate treatment in a timely manner. In an effort to develop a rational way to diagnose and treat patients with CPP, a panel of leaders in urology, gynecology, urogynecology and general women's health met to review recent literature, reach consensus and formulate 2 algorithms, one for diagnosing and the other for managing IC/PBS. This article reflects the results of that meeting.

Chronic prostatitis/chronic pelvic pain syndrome and male interstitial cystitis: enigmas and opportunities.

Recently, it has been recognized that interstitial cystitis (IC) in males is a more common clinical entity than was previously thought. Further, increasing evidence suggests clinical and pathogenetic similarities between male IC and chronic nonbacterial prostatitis (CP)/chronic pelvic pain syndrome. In this article, we highlight the similarities and differences between male IC and CP and review the presentation, diagnosis, and treatment of IC in men, with particular attention to those who have received an initial diagnosis of CP.

Successful management of interstitial cystitis in clinical practice.

Primary care physicians, urologists, and gynecologists have the opportunity to detect interstitial cystitis (IC) in its early stages in symptomatic patients and provide effective treatment before the disease progresses. In this article, we present guidelines for clinical practice management and coding for reimbursement for the care of patients with IC. Important issues in the management of IC are presented, including appropriate Current Procedural Terminology (CPT) coding for office visits and procedures associated with diagnosis and treatment of the disease. Excellent IC care can be integrated into a successful clinical practice with appropriate clinical management and coding for reimbursement.

Epidemiology and quality of life.

Once thought to be a rare condition, PBS/IC is being increasingly recognized as an important cause of CPP. It can exist either as a solitary disorder or in conjunction with other gynecologic or urologic disorders. The true prevalence of PBS/IC is hard to determine because most patients remain undiagnosed, although it is now thought to occur in up to 7.5% of the general female population and in 38-85% of women who present with CPP. Because the bladder has been insufficiently considered as a component of pelvic pain, many patients with PBS/IC may be misdiagnosed and inappropriately treated for years. It is critical for all clinicians, and especially gynecologists, who are often the first physicians from whom a woman with CPP will seek treatment, to consider PBS/IC in their patients who complain of pelvic pain, particularly when it occurs with urinary symptoms. The hallmark features of PBS/IC are irritative voiding and CPP. A minority of patients have classic ulcers and most have glomerulations, although it is not always necessary to establish these features to make the diagnosis. With careful questioning, most patients, in fact, can be identified by symptomatology, a medical history and a physical examination. Cystoscopy may be useful to rule out other conditions or to evaluate microscopic hematuria, which may be found in these patients. PBS/IC should be correctly diagnosed as early in the disease course as possible in order to avoid debilitating detriments to the patients' QOL in multiple domains. When symptoms of PBS/IC are recognized early on, treatment can be initiated when it is most likely to have a successful outcome. Although evidence-based clinical practice guidelines for IC/PBS are not available, partly because there is a lack of consensus on the definition and etiology of IC, clinicians, both primary care providers and specialists, can be reassured that there are diagnostic and treatment options that are simple to administer and have been demonstrated to be safe and effective.

Intravesical resiniferatoxin for the treatment of interstitial cystitis: a randomized, double-blind, placebo controlled trial.

PURPOSE: Interstitial cystitis is a painful bladder condition of unknown etiology and poorly understood pathophysiology. Current therapies have met with limited success. Vanilloid receptor agonists such as resiniferatoxin (RTX) desensitize C-fibers that transmit pain; it is hypothesized that such drugs will be effective in the treatment of interstitial cystitis and painful bladder syndrome by decreasing the pain that leads to urinary frequency and urgency. MATERIALS AND METHODS: A randomized, double-blind, placebo controlled study was conducted in 163 patients with interstitial cystitis. Participants were randomly assigned to receive a single intravesical dose of 50 ml of either RTX 0.01 microM, 0.05 microM, 0.10 microM, or placebo. Safety and efficacy was evaluated over 12 weeks. The primary efficacy endpoint was the Global Response Assessment, a 7-point scale rating overall change in symptoms of interstitial cystitis after 4 weeks. Secondary efficacy endpoints included reduction in pain, urgency, frequency, nocturia, average void volume, and the O'Leary-Sant Symptom and Problem Indexes. RESULTS: RTX did not improve overall symptoms, pain, urgency, frequency, nocturia, or average void volume during 12 weeks followup. RTX resulted in a dose-dependent increase in the incidence of instillation pain, but was otherwise generally well tolerated. CONCLUSIONS: In the largest prospective, randomized clinical trial reported to date with intravesical vanilloid therapy, single administration of RTX at doses of 0.01 microM to 0.10 microM was not effective in patients with interstitial cystitis.

Pentosan polysulfate sodium therapy for men with chronic pelvic pain syndrome: a multicenter, randomized, placebo controlled study.

PURPOSE: We evaluated the efficacy and tolerability of pentosan polysulfate sodium (PPS) for the treatment of men with chronic pelvic pain syndrome (CPPS), National Institutes of Health (NIH) category III. MATERIALS AND METHODS: In a 16-week double-blind study 100 men with a clinical diagnosis of CPPS were randomized to receive 300 mg PPS or placebo 3 times daily. Clinical Global Improvement (CGI) was the primary outcome measure. Additional outcome measures were the NIH-Chronic Prostatitis Symptom Index (CPSI), Subjective Global Assessment and Symptom Severity Index assessment tools. RESULTS: Significantly more patients receiving PPS experienced moderate to marked improvement based on CGI assessment (18 or 37% vs 8 or 18%, p = 0.04). However, mean CGI scores were not significantly different between the PPS group (1.0) and placebo groups (1.0 vs 0.6, p = 0.107). All NIH-CPSI domains suggested a positive effect for PPS and for total NIH-CPSI the difference approached statistical significance (-5.9 or 22% vs -3.2 or 12%, p = 0.068). The PPS group showed significantly greater improvement in NIH-CPSI quality of life domain scores than the placebo group (-2.0 or 22% vs -1.0 or 12%, p = 0.031). Of patients receiving PPS 67% and 80% of those receiving placebo completed the 16-week study. Diarrhea, nausea and headache were the most common adverse events. CONCLUSIONS: Pentosan polysulfate (900 mg daily) was more likely than placebo to provide relief for CPPS symptoms.

Interstitial cystitis, chronic nonbacterial prostatitis and chronic pelvic pain syndrome in men: a common and frequently identical clinical entity.

PURPOSE: In this ongoing review we characterize interstitial cystitis in men, identifying multiple clinical factors in the diagnosis and treatment of men with interstitial cystitis. MATERIALS AND METHODS: An ongoing and retrospective chart review of 92 men with interstitial cystitis within our large single specialty practice was performed. Presenting complaints, duration of symptoms, epidemiology, and clinical and physical findings were reviewed. RESULTS: All patients met National Institute for Diabetes and Digestive and Kidney Diseases criteria for the diagnosis of interstitial cystitis. Of the patients 83% were white and 17% were American Indians of Cherokee descent. Average patient age at diagnosis was 51 years and average duration of symptoms was 8.8 years. The most commonly reported initial complaints were mild suprapubic discomfort, which rapidly progressed in an average of 21/2 years to severe suprapubic discomfort, severe dysuria and severe urinary frequency. Sexual dysfunction occurred in 60% of patients with painful ejaculation. The most common physical findings were suprapubic tenderness to palpation and anterior rectal wall tenderness on digital rectal examination. Of the patients 40% had microscopic hematuria. All patients demonstrated severe glomerulations under anesthesia with cystoscopy and hydraulic distention of the bladder. Average bladder volume was 510 cc. CONCLUSIONS: Interstitial cystitis in males appears to be more common than historically reported. Interstitial cystitis in males and patients with chronic pelvic pain syndrome and chronic nonbacterial prostatitis share many clinical findings. A higher incidence of interstitial cystitis had been found in American Indian males of Cherokee descent and deserves further investigation.

Economics of interstitial cystitis in clinical practice.

Urologists may be concerned that treatment of patients with interstitial cystitis (IC) is not economically feasible, and the time spent on these patients could be used for more profitable urologic therapy. However, care of IC patients can provide urologic practices with increased revenue opportunities through a wide range of procedures, including IC evaluation and management, treatment planning, and diagnostic, therapeutic, and even surgical techniques. Current Procedural Terminology (CPT) and evaluation and management (E&M) charge codes are provided for many types, levels, and complexities of IC procedures. Some of these treatments may use physician extenders who generate profits without additional overhead costs. Further, IC therapy may involve the use of many in-office services, such as urodynamics, biofeedback, and peripheral nerve stimulation that can be economically profitable. Rather than being an economic drain, patients with IC can enhance the profitability of a urologic practice while they receive much needed care.