BACKGROUND: Overactive bladder (OAB) condition is a chronic disease characterized by urinary urgency with or without urge incontinence and frequency. This has caused a huge economic burden that has affected the quality of life of patients. OBJECTIVE: To determine the efficacy of OAB medication on the decrease of overactive bladder symptoms between solifenacin and mirabegron in men who underwent TURP. METHODOLOGY: The current Randomized controlled trial was done at the Department of Urology, IKD, Peshawar from 01-08-2021 to 01-02-2022.This study was conducted on 90 Male patients of age 30 to 70 years divided in two groups. Patients with BPH who underwent TURP with no active UTI and no gross hematuria were included. Patients who had overt neurological diseases such as cerebrovascular disease, senile dementia or spinal cord injury, patients having severe medical disease and completely immobile and having postvoid residual volume (PVR) larger than 150ml were excluded. Efficacy of improvement in OAB symptoms in both groups was assessed. RESULTS: This study was conducted on 90 patients divided in two group. Group A received mirabegron and group B received solifenacin. In group A OAB symptoms showed significant improvement as compared to group B. 35 (62.5%) patients in group A showed improvement in OAB symptoms and 21 (37.5%) patients in group B showed improvement. The difference was statistically significant (P = 0.002). CONCLUSION: In our study the efficacy of OAB medication on the decrease of overactive bladder symptoms of solifenacin was 35 (62.5%) and mirabegron was 21 (37.5%) in men who underwent TURP.
Overactive bladder (OAB) condition is a chronic disease characterized by urinary urgency with or without urge incontinence and frequency .This has caused a huge economic burdens that have affected the quality of life of patients 1,Urinary frequency, urgency and urge incontinence are common symptoms that occur in patients after transurethral prostatectomy (TURP) or transurethral incision of the prostate (TUIP)3. Patients usually complaining of these overactive bladder (OAB) symptoms.
The causes of post-prostatectomy Over Active Bladder might be detrusor over activity (DO) before TURP, increase afferent input due to acute inflammation after TURP, or a weak urethral sphincter which cannot hold urine at the bladder capacity. Antimuscarinics and beta-3 adrenoceptor agonist are two different classes of medication for OAB4. Around 70% of patients can improve symptoms after treatment with antimuscarinics and has been widely used to treat OAB. Beta-3 adrenoceptor agonist (mirabegron) can also decrease detrusor over activity. It also results in improvement in OAB symptoms. Combination treatment of solifenacin 5mg plus mirabegron 25 or 50mg was more effective than mirabegron 50mg alone, but with more anticholinergic side effects5. However, antimuscarinics might decrease detrusor contractility and result in increase of postvoid residual (PVR) volume. Recent studies reveal that mirabegron does not impair detrusor contractility or increase post void residual volume6.
Under this consideration, mirabegron has been widely used in the management of male lower urinary tract symptoms (LUTS) due to benign prostate hyperplasia (BPH)7. One study showed that the OAB symptoms of 83 % of patients get improved with Mirabegron while 56% percent with solifenacin8
However, there has been no such research studies to compare which drug provides more benefit to decrease the OAB symptoms severity immediately after TURP. This study tries to compare the therapeutic efficacy between solifenacin and mirabegron in men with BPH and having OAB symptoms immediately after TURP.
Study Design: 01-08-2021 to 01-02-2022 Sample Size: Sample size for this trial will be based on the previously reported improvement in OAB symptoms with Mirabegron & Solifenacin, 83.3% & 56 % respectively8, taking 95% confidence interval and power of 80%. It is a total number of 90 patients, 45 patients in each group using WHO sample size calculator. Sampling technique: consecutive non probability consecutive sampling. Inclusion Criteria: Male patients of age 30 to 70 years Male patients with BPH and undergo TURP . Patients void smoothly after catheter removal. No active urinary tract infection. No gross hematuria or blood clot obstruction. Exclusion Criteria: Patients have overt neurological diseases such as cerebrovascular disease, senile dementia or spinal cord injury. Patients have severe medical disease and completely immobile. Patients have postvoid residual volume (PVR) larger than 150ml. The above-mentioned conditions may act as confounders and if included will introduce bias in study results. DATA COLLECTION PROCEDURE After acceptance of the synopsis by CPSP, this study was conducted in the Department of Urology Institute of Kidney Diseases , Peshawar. Patients fulfilling the study criteria were recruited for the study. Informed Consent were taken from all the included patients. Patients were allocated randomly into two equal groups by blocked randomization, group A (Mirabegron ) & group B (solifenacin). History, examination, laboratory investigations (urinalysis, random blood sugar, complete blood count, coagulation profile, ALT, AST and serum creatinine) and radiological investigations (pelvi-abdominal ultrasonography with post-void ) done for all patients. Group A patients received solifenacin 5mg orally once-daily while group B patients received Mirabegron 50mg orally once –daily. Duration for taking these OAB medications for both groups were for four weeks from baseline after catheter removal. Patients were assessed after every week for Overactive bladder symptoms. Those who lost follow up werr replaced by recruiting new patients using the same sampling technique, strictly following the study criteria. All the information obtained were recorded on a pre-designed proforma. DATA ANALYSIS PROCEDURE Data were entered in SPSS version 21.0. Mean ± SD were calculated for variables like patient’s age and prostate size .Frequencies & percentages were calculated for variables like urgency urge incontinence and decrease in OAB symptoms of both groups. The comparison of effectiveness (as per operational definitions) were made using Chi-Square Test. P-value of 0.05 or less was considered as significant. Improvement in overactive bladder symptoms in both the groups were stratified among age, urgency, day and night time frequency and urge incontinence to see effect modification. Post-stratification Chi-Square Test was applied keeping P-value of 0.05 or less as significant. All results were presented in the form of tables and graphs.
This study was conducted on 90 patients divided in two group. Group A received mirabegron and group B received solifenacin. The mean age in group A was 50.89±11.56 and mean age in group B was 53.02±11.07 years. Mean prostate size in group A was 50.31±5.66 gm and 50.77±5.9 gm in group B (Table 1). According to age distribution there were 25 (58.1%) in the age range of 30 to 50 years in group A and 18 (41.9%) in group B. There were 20 (42.6%) patients in the age range of 31 to 70 in group A and 27 (57.4%) in group B. (Table 2). In group A OAB showed significant improvement as compared to group B. 35 (62.5%) patients in group A showed improvement in OAB and 21 (37.5%) patients in group B showed improvement.
The difference was statistically significant (P = 0.002). (Table 3). According to day time frequency in group A 30 (75%) patients had frequency < 4 times, 11 (34.4%) had frequency 4 to 5 times and 4 (22.2%) had frequency > 5 times. In group B 10 (25%) had frequency < 4 times, 21 (65.6%) had frequency between 4 to 5 times and 14 (77.8%) had frequency > 5 times. (Table 4). According to night time frequency in group A 30 (73.2%) patients had frequency < 4 times, 10 (24.4%) patients had frequency between 4 to 5 times and 5 (62.5%) had frequency > 5 times. In group A 11 (26.8%) had frequency < 4 times, 31 (75.6%) had frequency between 4 to 5 times and 3 (37.5%) had frequency > 5 times. (Table 5). In group A 11 (23.4%) patients had urgency/urgency incontinence and in group B 36 (76.6%) had urgency/urgency incontinence. (Table 6). Stratification of OAB improvement in both groups w.r.t age, day time frequency, night time frequency and urgency/urgency incontinence can be seen from table no 7 to table no 10.
Table 1: Descriptive statistics (N = 90)
|
Groups |
Age (years) |
Prostate size (gm) |
|
|
Group A (Mirabegron) (n = 45) |
Mean |
50.89 |
50.3111 |
|
Std. Deviation |
11.566 |
5.66417 |
|
|
Group B (Solifenacin) (n = 45) |
Mean |
53.02 |
50.7778 |
|
Std. Deviation |
11.075 |
5.97300 |
|
Table 2: Age distribution of the enrolled patients
|
|
Age distribution |
Total |
||
|
30 to 50 |
31 to 70 |
|||
|
Groups |
Group A (Mirabegron) |
25 |
20 |
45 |
|
58.1% |
42.6% |
50.0% |
||
|
Group B (Solifenacin) |
18 |
27 |
45 |
|
|
41.9% |
57.4% |
50.0% |
||
|
Total |
43 |
47 |
90 |
|
|
100.0% |
100.0% |
100.0% |
||
Table 3: Improvement in OAB between both groups
|
|
Improvement in OAB symptoms |
Total |
P value |
||
|
Yes |
No |
||||
|
Groups |
Group A (Mirabegron) |
35 |
10 |
45 |
0.002 |
|
62.5% |
29.4% |
50.0% |
|||
|
Group B (Solifenacin) |
21 |
24 |
45 |
||
|
37.5% |
70.6% |
50.0% |
|||
|
Total |
56 |
34 |
90 |
||
|
100.0% |
100.0% |
100.0% |
|||
Table 4: Day time frequency in OAB patients
|
|
Day time frequency |
Total |
|||
|
< 4 times |
4 to 5 times |
> 5 times |
|||
|
Groups |
Group A (Mirabegron) |
30 |
11 |
4 |
45 |
|
75.0% |
34.4% |
22.2% |
50.0% |
||
|
Group B (Solifenacin) |
10 |
21 |
14 |
45 |
|
|
25.0% |
65.6% |
77.8% |
50.0% |
||
|
Total |
40 |
32 |
18 |
90 |
|
|
100.0% |
100.0% |
100.0% |
100.0% |
||
Table 5: Night time frequency in OAB patients.
|
|
Night time frequency |
Total |
|||
|
< 4 times |
4 to 5 times |
> 5 times |
|||
|
Groups |
Group A (Mirabegron) |
30 |
10 |
5 |
45 |
|
73.2% |
24.4% |
62.5% |
50.0% |
||
|
Group B (Solifenacin) |
11 |
31 |
3 |
45 |
|
|
26.8% |
75.6% |
37.5% |
50.0% |
||
|
Total |
41 |
41 |
8 |
90 |
|
|
100.0% |
100.0% |
100.0% |
100.0% |
||
Table 6: Frequency of urgency/Urgency incontinence
|
|
Urgency/Urgency incontinence |
Total |
||
|
Yes |
No |
|||
|
Groups |
Group A (Mirabegron) |
11 |
34 |
45 |
|
23.4% |
79.1% |
50.0% |
||
|
Group B (Solifenacin) |
36 |
9 |
45 |
|
|
76.6% |
20.9% |
50.0% |
||
|
Total |
47 |
43 |
90 |
|
|
100.0% |
100.0% |
100.0% |
||
Urinary urgency, frequently accompanied by frequency and nocturia, with or without urgency urinary incontinence (UUI), is classified as overactive bladder (OAB) . OAB is frequent in elderly women, and it has a negative impact on their health-related quality of life9. Many medicines, mostly anti-muscarinic medications, are used in the current pharmacological approach to OAB therapy. Anti-muscarinic drugs, on the other hand, are linked to a high rate of side effects such dry mouth and constipation. Mirabegron, a 3-adrenoceptor agonist with a mode of action different from anti-muscarinics, was developed in 2011 for the treatment of OAB. The 3-adrenoceptor is responsible for human detrusor relaxation and bladder urine storage10. Mirabegron was found to be effective in treating the symptoms of OAB and had a low rate of side effects. When tolterodine is taken as an anti-muscarinic, the incidence of dry mouth is equivalent to that seen with a placebo and three to five times less than when tolterodine is used as an anti-muscarinic. Several studies have shown that both mirabegron and anti-muscarinics improve OAB symptoms, with no statistically significant differences observed between the 2 treatments11. Although anti-muscarinic medicines are the first-line treatment for OAB, they can cause unpleasant side effects, which can lead to poor adherence to the prescribed medications. The most prevalent reason for discontinuation is a bad tongue. In light of this, we must consider which medications should be utilised first in the treatment of OAB.12 Mirabegron is the first 3-adrenoceptor agonist approved for the treatment of OAB in clinical practise. It has a distinct mode of action than anti-muscarinic drugs. Mirabegron has been demonstrated in numerous studies to be effective in treating the symptoms of OAB, and that its efficacy is comparable to that of anti-muscarinic drugs. Bayesian mixed treatment comparisons (MTCs) were used to evaluate medications for OAB efficacy and tolerability, according to Khaled et al.12. According to the MTCs in a study8, mirabegron 50 mg was as effective as anti-muscarinics in reducing the frequency of micturition incontinence and UUI episodes, with the exception of solifenacin 10 mg, which was more effective than mirabegron 50 mg in reducing the frequency of micturition incontinence and UUI episodes. The average change in the baseline number of micturitions for solifenacin 5 mg versus mirabegron 50 mg was -0.24 micturition episodes per day, according to this study. The average daily number of UUI episodes was - 0.294. Treatments with solifenacin 5 mg were somewhat more successful than those with mirabegron 50 mg, but the difference was not significant13. Our study showed that the patients in group A who received mirabegron showed significant improvement in OAB as compared to group B which received solifenacin. In group A OABsymptoms showed significant improvement as compared to group B. 35 (62.5%) patients in group A showed improvement in OAB symptoms and 21 (37.5%) patients in group B showed improvement. The difference was statistically significant (P = 0.002). Our findings are in agreement with a study8 which showed significant improvement OAB symptoms in patients receiving mirabegron as compared to patients receiving solifenacin.
In our study the efficacy of OAB medication on the decrease of overactive bladder symptoms of solifenacin was 35 (62.5%) and mirabegron was 21 (37.5%) in men who underwent TURP.