Effect of intraurethral captopril gel on the recurrence of urethral stricture after direct vision internal urethrotomy: Phase II clinical trial

Abstract

Objective: The purpose of this study is to evaluate the effect of intraurethral captopril gel as an antifibrotic agent on patients with urethral stricture. Materials and Methods: In the first phase of clinical trial, 13 rabbits were included and local side-effects of captopril gel were evaluated. In the second phase, 56 patients were enrolled from April 2004 to January 2006. After internal urethrotomy the patients were classified into three patient groups: (i) received placebo gel (group I); (ii) received 0.1% captopril gel (group II); and (iii) instilled 0.5% captopril gel intraurethrally (group III). Results: In phase I, no significant local side-effects were seen in the urethra of rabbits. In phase II, the mean age of the patients was 39.5 and the mean follow-up duration was 16 months. The most common etiology of the urethral stricture in the patients was iatrogenic (35.7%), most of their strictures had a depth of 0.5 cm or less (67.8%), and the length of most strictures was between 1 and 2 cm (41.1%). The patients' maximum urine flow increased more in groups II and III, than in group I (P < 0.04, P < 0.05, respectively). The recurrence rate was less in groups II and III than in group I (P < 0.05). In terms of the maximal urine flow and recurrence rate, no significant difference was seen between group II and group III (P = 0.13, P = 0.21, respectively). Conclusion: Captopril gel is a safe, effective and non-toxic agent for decreasing the recurrence rate of the urethral stricture after internal urethrotomy. However, more studies, including more cases and a longer follow up, are needed to prove the effect of captopril gel on patients' urethra.

Antifibrotic Role of Captopril after Ureteral Injury

“…The angiotensin-converting enzyme inhibitors (ACE-I) can inhibit the angiotensin-converting enzyme and block the conversion of angiotensin I to angiotensin II, thereby reducing angiotensin II levels within the fibrotic tissue, and then reducing TGF-β expression, resulting in an antifibrosis function [15,16,17]. Shiraz et al [1] have reported in patients with urethral stricture, after urethral incision, early administration of ACE-I gel in the urethra could significantly reduce the recurrence rate of urethral stricture. Currently, angiotensin-converting enzyme inhibitors represented by captopril have become an important treatment of congestive heart failure, liver fibrosis, pulmonary fibrosis and other fibrotic diseases.…”

“…Pathological examination proved that fibrotic scarring is the major pathological characteristic responsible for upper urinary tract obstruction. For urethra stricture, Shiraz et al [1] have reported that early administration of ACE-I gel in the urethra after urethral incision could significantly reduce the recurrence rate of urethral stricture. However, to our knowledge, up till now, no effective clinical intervention has been found to mitigate or stop such a fibrotic process after ureteral injury.…”

Minimally invasive treatment of urethral strictures in men

“…Based on experience with the antifibrotic properties of the angiotensin-converting enzyme-inhibitor captopril, a phase II clinical trial of intraurethral captopril gel on the recurrence of urethral stricture after OIU/DVIU was conducted [35]. Men 18-79 years old (mean, 39.5 ± 15.3) were followed for 6-30 months (mean, 16).…”

Halofuginone-Coated Urethral Catheters Prevent Periurethral Spongiofibrosis in a Rat Model of Urethral Injury

“…Strictures are associated with alteration of the collagen ratios with a significant increase in type I collagen. 7 To prevent recurrence of strictures, various pharmacologic therapies have been used locally [8][9][10][11] ; however, these substances have not been specific for collagen type I, and therefore, further research into more targeted therapies may produce improvement in outcomes. Halofuginone (HF) is a potent inhibitor of collagen type I 12 and has been demonstrated in previous studies to prevent stricture formation when given systemically.…”