Intravesical bacillus Calmette-Guerin and dimethyl sulfoxide for treatment of classic and nonulcer interstitial cystitis: a prospective, randomized double-blind study. The efficacy of intravesical bacillus Calmette-Guerin in the treatment of interstitial cystitis: long-term followup. Intravesical resiniferatoxin for the treatment of interstitial cystitis: a randomized, double-blind, placebo controlled trial. A prospective, double-blind, randomized cross-over study evaluating changes in urinary pH for relieving the symptoms of interstitial cystitis. A controlled study of dimethyl sulfoxide in interstitial cystitis. A randomized controlled trial of intravesical bacillus calmette-guerin for treatment refractory interstitial cystitis. The efficacy of intravesical Tice strain bacillus Calmette-Guerin in the treatment of interstitial cystitis: a double-blind, prospective, placebo controlled trial. A placebo-controlled study of intravesical pentosanpolysulphate for the treatment of interstitial cystitis. Interstitial cystitis: bladder training with intravesical oxybutynin.
We conducted a prospective, double-blind study with a crossover design of intravesical bacillus Calmette-Guerin (BCG) and dimethyl sulfoxide to determine whether patients with classic and nonulcer interstitial cystitis, respectively, might benefit from either regimen.
                A total of 21 patients, including 11 with classic and 10 with nonulcer interstitial cystitis, randomly underwent treatments with intravesical BCG or dimethyl sulfoxide and, if not improved, were treated with the other substance after a washout period. All 21 patients were evaluated with symptom questionnaires, including a visual analog pain scale and voiding diaries.
                Regardless of regimen, there was no improvement in maximal functional capacity. There was a reduction in urinary frequency following dimethyl sulfoxide treatment but only in the classic subtype (p <0.05), whereas no reduction was seen following BCG in either subtype. A substantial pain decrease was noted in classic (p <0.05) as well as nonulcer (p <0.05) interstitial cystitis following dimethyl sulfoxide.
                Intravesical BCG has been presented as a promising new option for treatment of interstitial cystitis. We failed to demonstrate benefit from this treatment. Dimethyl sulfoxide had no positive effect on maximal functional capacity but resulted in a significant reduction in pain and urinary frequency, although only in patients with classic interstitial cystitis. Interstitial cystitis is a severe debilitating bladder disease characterized by unrelenting pelvic pain and urinary frequency. A prospective, double-blind, placebo controlled study of the use of intravesical bacillus Calmette-Guerin (BCG) in the treatment of interstitial cystitis was recently completed with a mean followup of 8 months. Results demonstrated a 60% BCG response rate, compared to a 27% placebo response rate. We now report the long-term followup results of those patients who received intravesical BCG.
                Subjects randomized to receive BCG were followed at routine intervals with questionnaires and voiding diaries identical to those in the blinded study. Adverse events were closely monitored in the treatment and followup phases of the study. Subject baseline values were compared to followup data.
                Of the BCG responders mean followup was 27 months (range 24 to 33), and 8 of 9 (89%) continue to have an excellent response in all parameters measured. The global interstitial cystitis survey improved 70%, daily voids decreased 31%, nocturia improved 54%, mean voided volume increased 61%, pelvic pain decreased 81%, vaginal pain decreased 71%, urgency decreased 71% and dysuria decreased 82%. Overall well-being improved 54% and the Rand-36 quality of life survey overall improved 64%. In 86% of the patients (6 of 7) dyspareunia resolved. Of the initial BCG nonresponders there was no significant difference in interstitial cystitis symptomatology from baseline to last followup, suggesting that BCG does not worsen interstitial cystitis symptoms. No long-term adverse events from BCG were noted.
                Intravesical Tice BCG is safe, effective and durable in the treatment of interstitial cystitis. Of those patients who received only 6 weekly treatments and responded favorably 89% continue to have an excellent response with followup ranging from 24 to 33 months. 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.
                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.
                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.
                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. To provide evidence for the clinical efficacy of changes in urinary pH on the pain associated with interstitial cystitis (IC).
                A prospective, randomized, double-blind cross-over study was conducted with 26 women with IC between 2000 and 2002, consisting of cross-over instillations of urine at physiological pH (5.0), and neutral buffered pH (NaH(2)PO(4) buffered to pH 7.5). The outcome measured was the subjective symptom of pain assessed using a visual analogue scale at baseline, after the initial instillation of solution, at washout, and after the crossover instillation. Data were analysed using repeated-measures analysis of variance.
                There was no statistically significant difference between the mean (sd) change from baseline pain scores after instilling neutral buffered solution, at 0.50 (2.78), and acidic solution, at 0.33 (3.43) (P = 0.85). Secondary outcomes were analysed, including baseline variability and treatment-order effects; neither were significantly different between the groups.
                There was no statistically significant difference in subjective pain scores on instilling urine at physiological pH or sodium-phosphate buffered saline in these patients with IC. Further work is required to define the role, if any, of urinary pH in the pathophysiology and treatment of IC. To evaluate the effectiveness of dimethyl sulfoxide in the treatment of patients with biopsies suggestive of interstitial cystitis, 33 patients underwent a controlled crossover trial. Patients were allocated randomly to receive 50 per cent dimethyl sulfoxide or placebo (saline). The medication was administered intravesically every 2 weeks for 2 sessions of 4 treatments each. Response was assessed urodynamically and symptomatically. Thirty women and 3 men (mean age 48 years and mean duration of symptoms 5.5 years) were entered into the study. No significant side effects to dimethyl sulfoxide were noted. When assessed subjectively, 53 per cent of dimethyl sulfoxide treated patients were markedly improved compared to 18 per cent of the placebo treated patients. Of the dimethyl sulfoxide group 93 per cent had objective improvement versus 35 per cent of the placebo group. Thus, dimethyl sulfoxide proved to be superior to placebo in the objective and subjective improvement of patients with interstitial cystitis. We compared intravesical bacillus Calmette-Guerin (BCG) to placebo instillations in patients with treatment refractory interstitial cystitis (IC).
                Subjects who met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC, and reported at least moderate pain and frequency for a minimum of 6 months before study entry, were randomized to 6 weekly double-blinded intravesical instillations of either BCG or placebo, and then followed for a total of 34 weeks. The primary outcome was a patient reported global response assessment at week 34, supplemented with medications for IC during weeks 31 to 34. Secondary outcomes included a 24-hour voiding diary, pain, urgency, validated IC symptom indexes and adverse events. The target sample size was 260 participants, designed to detect a difference in response rates between placebo and BCG of 30% and 50%, respectively.
                A total of 265 participants were randomized and 17 (6%) patients withdrew from study. The response rates for the primary outcome were 12% for placebo and 21% for BCG (p = 0.062). Small improvements were observed for all secondary outcomes, some more so with BCG, but these differences were of borderline statistical significance. Although a large number of adverse events were reported in the BCG arm, there was no statistically significant difference between the treatment arms in overall adverse event rates.
                Although the BCG safety profile was acceptable, the response rate for the primary outcome was low. Effective medical treatment for patients with moderate to severe interstitial cystitis remains elusive. Interstitial cystitis is a debilitating bladder disease of unknown etiology with no cure. A recent report suggested that bacillus Calmette-Guerin (BCG) may be effective in the treatment of interstitial cystitis. A randomized, prospective, double-blind, placebo controlled trial to evaluate the safety and efficacy of intravesical BCG in treating interstitial cystitis was done.
                Patients meeting the National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases criteria for interstitial cystitis received 6 weekly instillations of Tice strain BCG or placebo. Periodic questionnaires, voiding diaries and cystometrograms were obtained. A total of 30 evaluable subjects was enrolled in the study with a mean followup of 8 months (range 6 to 13). Based on an exit questionnaire a responder was defined as one who rated the interstitial cystitis symptoms as moderately improved or better.
                A 60% BCG response rate was noted, compared to a 27% placebo response rate. Minimum voided volume and quality of life improved in the BCG group compared to placebo. Adverse events were similar in each group, mostly irritative in nature, and no significant systemic events were noted.
                Intravesical Tice strain BCG appears to be safe and efficacious in the treatment of interstitial cystitis. Additional studies must be performed to confirm the results of this pilot study. To evaluate the therapeutic efficacy of intravesical pentosanpolysulphate (PPS) compared with placebo in patients with interstitial cystitis (IC).
                Twenty patients who fulfilled the diagnostic criteria for IC participated in a double-blind placebo-controlled study; 10 received intravesical PPS (300 mg in 50 mL of 0.9% sodium chloride) applied twice a week for 3 months and the other 10 received a placebo. Symptomatic relief and objective variables (bladder capacity voiding volumes and urinary frequency) were assessed after 3 months and the long-term outcome of those continuing treatment was determined.
                Of the patients treated with PPS, four gained significant symptomatic relief compared with only two receiving placebo. Only the urodynamic bladder capacity showed a statistically significant increase in patients treated with PPS (P = 0.047). At 18 months from the start of the study, the symptoms were relieved in eight patients while still receiving PPS instillations and in four without treatment.
                These results suggest that intravesical PPS is an effective option for the treatment of IC and shows that the intravesical application of PPS is a safe treatment with no important side-effects. We assess the efficacy of intravesical administration of oxybutynin chloride in patients with interstitial cystitis.
                The study included 36 women with a mean age of 45 years with a diagnosis of interstitial cystitis. Patients were treated with gradual intravesical instillation of saline oxybutynin solution (oxybutynin group) or gradual filling of simple saline (control group). Evaluation parameters consisted of symptom problem index, voids per day, volume per void, functional bladder capacity, volume at first sensation, cystometric bladder capacity and cystometric volume at first sensation.
                Statistically significant improvement of all evaluated parameters was found in both groups. When comparing the outcomes statistically significant improvement of parameters favored the oxybutynin group.
                Bladder training alone produces a satisfactory result by gradually expanding the bladder, and an additional statistically significant improvement is evident with intravesical oxybutynin.
Overall, the evidence base for treating PBS/IC using intravesical preparations is limited and the potential for meta-analysis reduced by variation in the outcome measures used. The quality of trial reports was mixed and in some cases this precluded any meaningful data extraction. BCG and oxybutin are reasonably well-tolerated and evidence is most promising for these. Resiniferatoxin showed no evidence of effect for most outcomes and caused pain, which reduced treatment compliance. There is little evidence for the other treatments included in this review. Randomised controlled trials are still needed and study design should incorporate outcomes that are most relevant to these with PBS/IC and should be standardised.