A Study On Solifenacin Versus Placebo For Return To Continence In Patients After Robot-Assisted Radical Prostatectomy

Review and article summarize the article: A Randomized, Double-Blind, Solifenacin Succinate versusPlacebo Control, Phase 4, Multicenter Study EvaluatingUrinary Continence after Robotic Assisted Radical Prostatectomy.

Objective of the Study

Urinary incontinence also known as involuntary urination is a bladder dysfunction which causes involuntary urination or uncontrolled leakage of urine (Homma, 2008). Several studies have been conducted in the medical setting for deeper knowledge regarding this problem (McGaghie et al., 2010). One such research was performed to evaluate solifenacin versus placebo in patient who were incontinent after catherer removal after robot-assisted radical prostatectomy. In this report, an article based on similar is reviewed. The article was set to examine solifienacin versus placebo on return to continence in patients who were still incontinent 7-21 days after catherter removal after robot-assited radical prostatectomy. The study has provided various information however it is necessary to understand the matter in detail which are related to the urine incontinence.

After the radical prostatectomy the urinary continence is a pivotal end point of the required trifecta outcome (Coelho et al., 2010). The article begins by giving out the same information regarding the potential of the urine continence. According to the article the recovering postoperative continence after RP is the large balance between the strength of the external sphincter and the viability and the impact of bladder compliance and detrusor instability. It is indeed the true fact that they are related to one another and help in balancing one another (Bianco et al., 2015). The article uses the findings of Rodriguez in the investigation that helped understanding the detrusor instability as a cofactor in prolonged incontinence. The arcitle have shown the absence of safety issues witin the phase I trial evaluating solifenacin in the post-RARP setting. The article’s post-RARP demonstrated few important points such as

• Absence of any significant safety issues with solifenacin after RARP
• The severely delayed return prediction that returned of continence which could not be established by the standard baseline preoperative assessment

The leakage degree in the first few days are catheter removal which is after RP may be the best predictor of prolonged incontinence. The article has stated the similar thing regarding the aspect (Overgård et al., 2008). It also said that 95% become able to stay without pad within the duration of 90 days. The article has also given insights about patients with post-prostatectomy incontinence that is with mixed urinary incontinence symptoms as well as those people with mixed urinary incontinence symptoms.

The study was done on the patients who were still incontinence 7-21 days after the catheter removal. The major purpose of the study was to assess the efficacy and safety of 12 weeks of treatment of solifenacin (Wood & Anger, 2014). Versus placebo. It was majorly in patients whose urinary incontinence required 2 to 10 PPD for 7 days consecutively after the catheter removal. The study’s primary objective was the continuous assessment of the time during the 12 weeks of treatment that is associated with solifennacin versus placebo. The secondary objective of the study was categorically assess the treatment effect on the patients who have successfully gained continence at 4, 8 and 12 weeks (Vardy et al., 2009).

Design of the Study

The design of the study was also done with in-depth research in the article. It found that men with newly diagnosed clinically localized prostate cancer, specifically who went through RARP were the main invited candidates to participate in the study in the meantime of Foley catheter removal. The participants received a PDA that is similar to a smartphone device. The device evaluated the use of daily pad and the drug use intake. The intake of drugs and the usage of pad were measured by the smartphone alike device PDA. The devices was used for the purpose mentioned as well as it would ring at night around 7 pm until the patient would provide the required information needed. The information required were regarding medication compliance and usage of pad. The answers that were provided were digitally encrypted and could not be edited for the any purpose which securely transmitted to designated servers. The patients were not provided with any economic incentives. However the pad used or given to the patients were given for free of any charge (Payne et al., 2012).

The treatment free screening and the wash out period was a 7-21 days. The patients who were recording 2 to 10 PPD for consecutively 7 days and were meeting the baseline criteria were capable for the treatment phase of the trail. They were randomized 1:1 to 5 mg solifenacin or placebo. In the week 4 which was based on efficiency and safety along with the investigator, it was found that the dose could be doubled to 10 mg once every day. Screening and end of the treatment were carried out onsite followed by the baseline and week 4 and week 8 visits that were telephone contact visits. The subjects who completed the PDA survey every day while the study was going on. Also, on 12 visits the subjects were asked to complete the AUASS with bother score, the ICIQ-SF and the WPAI at baseline (Lenders, 2010).

Sample size, power estimation and statistical analyses: based on safety analysis set all the safety analyses were conducted which is appreciable in this article. The randomized patients who have had at least one dose of double-blind study, medication were selected for the SAF which could be more specific. Also the FAS consisted of SAF patients who were in the primary efficiency variable had at least once post-baseline assessment. A log rank test stratified by center and baseline pad use was the method of estimating the treatment difference in time to continence at a 2-sided significance level of 0.05. At the end of 12 weeks patients who did not gain continence were censored. The treatment differences were tested between the patients who gained continence at the end of 12-week treatment and who did not (Wenzel et al., 2009).

Results of the Study

Result: a total of 1125 patients from 65 centers were consented to participate in the trail however 39 failed to enter data into the device. 623 patients constituted the SAF as 17 patients had not taken any study medications that were also excluded from the study analysis. Apart from one patient who was on placebo, every other SAF patients were included in the FAS. The primary outcome when measured among the 622 FAS patients there was no difference in the time to return to urinary continence from the baseline to the end of study. In the end it was found that there were no differences between treatment arms  in both who remained at 5 mg and the ones who increased to 10 mg daily at 4 weeks.

The secondary outcome measure was when analyzed it was found in the article that 91 of 313 were favoring solifenacin over placebo versus 66 of 309 patients were continent. In the overall perspective, both the patients experience significant decrease in the number of PPD that was used as the baseline to the study end. Of the 622 FAS subjects a total of 274 participated in the workforce before the study and of 127 144 patient on solifenacin as well as placebo returned to work by the end of the study. In the overall 73% of screened men became continent by the end of the trial and approximately 40% of men during the washout became continent and hence were not randomized.

The main idea of conducting the research was to find out the bladder dysfunction influences recovery of continence of urinary. However, there were certain limitations in the paper that are found. The UDS was an absolute necessary which are ignored in the paper. Along with the short-term evaluation there was need for long term intervention which was essential to see the changes causing bladder dysfunctional.

Conclusion:

In the end of the study, the article states that it was not statistically significant that the primary end point of time to urinary continence. However, the secondary end points of promotion of subject gained continence were statistically significant. Also, dry mouth was one of the  solifenacin side effect. No there notable safety observation was there and it is only in 1B of continence outcome that the study provides clinical evidences

References:

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Coelho, R. F., Rocco, B., Patel, M. B., Orvieto, M. A., Chauhan, S., Ficarra, V., ... & Patel, V. R. (2010). Retropubic, laparoscopic, and robot-assisted radical prostatectomy: a critical review of outcomes reported by high-volume centers. Journal of Endourology, 24(12), 2003-2015.

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Wood, L. N., & Anger, J. T. (2014). Urinary incontinence in women. Bmj, 349, g4531.