Priapism, a clinical disorder of erection, is associated with physical and psychological harm to patients. Its ischemic form is associated with penile pain and erectile tissue loss, potentially leading to permanent erectile dysfunction (ED).
Ischemic priapism is notably common in sickle cell disease patients. Given that recent studies have implicated the nitrergic pathway in its pathophysiology, this randomized, double-blind, placebo-controlled clinical trial investigated the safety and efficacy of a phosphodiesterase type 5 inhibitor, sildenafil, in preventing ischemic priapism in sickle cell disease (SCD) patients. Sickle cell disease patients aged 14 to 45 years who reported at least two weekly priapism episodes were recruited. Those with glomerular filtration rate less than 50 mL/min, clinical cirrhosis, pulmonary hypertension or significant alcohol use were excluded. This was a two-phase, single-center study conducted prospectively. In the double-blind phase (phase 1), 13 patients were randomized in a 1:1 ratio to receive daily sildenafil 50 mg or placebo for 8 weeks. In the subsequent 8-week open-label phase (phase 2), daily sildenafil 50 mg was given to all 8 remaining participants. Patients were instructed to take sildenafil in the mornings and without sexual stimulation. The primary outcome was a 50% reduction in the biweekly priapism episodes from the baseline of each respective trial phase. Subjective improvements in episode frequency and duration were used as secondary outcomes. A tiered scoring system was used to quantify the priapism episodes. Baseline scores were compared using the Wilcoxon rank sum test and the categorical outcomes were compared by Fisher exact test. No difference was found between the two initial groups in terms of age, alcohol use or smoking status. At the end of phase 1, no significant difference in the reduction of episodes by score tier was found between the two groups, either by intention-to-treat (50% in sildenafil group and 42. 9% in placebo group P = 1. 0) or per protocol (33. 3% in sildenafil group and 50% in placebo group P = 1. 0) analysis. Similarly, there was no difference between the groups for the secondary outcomes, by either analysis method. At the end of phase two, intention-to-treat demonstrated a 62. 5% reduction in primary outcome and per-protocol demonstrated a 66. 7% reduction in primary outcome. Both methods also reported improvements in secondary outcome in about one third of the patients for this phase. Adverse effects of sildenafil administration were rare and transient, consisting of flushing, abnormal vision and dyspepsia. These events were consistent with literature and not significantly different between the sildenafil and placebo groups. Interestingly, seven patients were hospitalized 14 times during the course of this study, most of which (10) were related to major priapism episodes. Of these 10 visits, only 2 occurred to patients' actively on sildenafil therapy and the remaining 8 occurred to placebo or nonadherent sildenafil patients.
Urology. 2015 Sep 29 [Epub ahead of print]
Aria Shakeri, Brandon Van Asseldonk, Dean S Elterman, Peter Black
Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. , Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. , Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. , Vancouver Prostate Centre, University of British Columbia.