INTRAVESICAL RESINIFERATOXIN FOR THE TREATMENT OF INTERSTITIAL CYSTITIS: A RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED TRIAL
Abstract
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 μM, 0.05 μM, 0.10 μM, 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 μM to 0.10 μM was not effective in patients with interstitial cystitis.
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From the From Stanford University School of Medicine, Stanford, California (CKP), Urology of Indiana, Indianapolis, Indiana (PGM), Urologic Specialists of Oklahoma and St. Johns Medical Center, Tulsa, Oklahoma (JBF), The Urology Center, Greensboro, North Carolina (RJE), Graduate Hospital, Philadelphia, Pennsylvania (KEW), The Connecticut Clinical Research Center, Waterbury, Connecticut (JPA), Advanced Research Institute, New Port Richey, Florida (RP-M), Integrity Medical Research, Seattle, Washington (KJ), William Beaumont Hospital, Royal Oak, Michigan (ACD), Madigan Army Medical Center, Tacoma, Washington (KJO), University of Kansas Medical Center, Kansas City, Kansas (TLG), The Cleveland Clinic, Cleveland, Ohio (SPV), and ICOS Corporation, Bothell, Washington (ASY, LRF)
