To evaluate a polycaprolactone (PCL)-based bioresorbable bulking agent for safety and efficacy in female patients with mild to moderate stress urinary incontinence (SUI) who attempted and failed prior pelvic floor muscle training. A high safety profile is expected due to the bioresorption profile of PCL and a sustained clinical effect is expected due to PCL induced neocollagenesis, where a scaffold of natural collagen (types I and III) forms around the microspheres. PCL is a well-known polymer which has been used successfully in numerous Food and Drug Administration (FDA) approved and Conformité Européenne (CE) marked medical devices and is fully bioresorbable.

50 female patients were treated by transurethral sub-mucosal injection with a novel PCL-based bulking agent. The mean age of these subjects was 47.5 years ± 12.2 ranging from 26-81 years with a median age of 47 years. To date, 49 subjects have completed the 3-month follow-up, 47 have completed the 6-month follow-up and 13 have completed the 12-month follow-up. Since this is a  24-month study, preliminary results presented here can be subject to change. Safety was assessed based on reported adverse events. Efficacy was assessed with the Stamey Grading System (SGS), Patient Global Impression of Severity (PGI-S) and Patient Global Impression of Improvement (PGI-I). Quality of life QoL was assessed with the International Consultation on Incontinence Questionnaire – Short Form (ICIQ-SF) and Incontinence Quality of Life (I-QOL) scale. ICIQ-SF severity was divided into the following categories: slight (1 – 5), moderate (6 – 12), severe (13 – 18) and very severe (19 – 21) according to Klovning et al. [1].

Initial mean treatment volume was 1.5mls ± 0.5 (n=49). 14/49 (28.6%) subjects were re-treated with a mean re-treatment volume of 1.3mls ± 0.4 (n=49). SGS improvements were 63.3% (cure-rate 42.9%) and 55.3% (cure-rate 42.6%) at 3- (n=49) and 6-month (n=47) follow-up, respectively. PGI-S improvements were 75.5% (cure-rate 53.1%) and 72.3% (cure-rate 44.7%) at 3- (n=49) and 6-month (n=47) follow-up, respectively. Results from the PGI-I show a high treatment success of 85.7% at 3-month (n=49) follow-up and 74.5% at 6-month (n=47) follow-up. Quality of Life (QoL) results show that the median ICIQ-SF scores improved from 13 (“severe”) at baseline to 7 and 6 (“moderate”) at 3- and 6-month follow-up, respectively. 87.8% and 70.0% of the subjects were improved on their I-QoL at 3- (n=49) and 6-month (n=47)  follow-up, respectively. Results are summarized in Table 1. 
Seven out of 49 subjects reported post-treatment related adverse events (AEs). AEs were mild in nature and resolved spontaneously by providing relevant medication and/or catheterization. Three AEs (6.0%) occurred directly post-treatment (hematuria, dysuria and urinary retention) and four AEs (8.0%) between treatment and the 6-month follow-up (urinary tract infection, urge incontinence, psoriasis and severe coughing). One serious AE (SAE) required hospitalization to treat urinary retention which was resolved with the use of a catheter.

The intermediate analysis suggests that PCL-based bulking agent treatment is both safe and effective, resulting in improvements in SUI severity and QoL, with a low adverse event rate. The study is ongoing and the amount of data and follow-up period will be extended out to 5 years, providing additional safety and efficacy data.

QoL measures are an essential end-point for measuring patients perceptions of the effects of incontinence treatments. Improvements in QoL shown here further demonstrate the efficacy of this PCL-based bulking agent. In addition to its efficacy, bioresorption is an attractive safety feature of the PCL-based bulking agent when compared to permanent materials. Preliminary results suggest that the bioresorbable PCL-based bulking agent is a promising safe and effective treatment option, and a valuable addition to the current treatment armament for female patients with mild to moderate SUI, who attempted and failed prior pelvic floor muscle training.

Klovning A, Avery K, Sandvik H, Hunskaar S. Comparison of two questionnaires for assessing the severity of urinary incontinence: The ICIQ-UI SF versus the incontinence severity index. Neurourol Urodyn. 2009;28(5):411-415.