Randomized, double-blind placeboand tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder

2004 BJU INTERNATIONAL | 93, 303–310


A この試験の結果は信頼できるか


Men and women aged ≥18 years with symptoms of OAB (including urgency, urge incontinence, or frequency) for ≥ 3 months were eligible for screening and study enrolment. To be eligible for randomization after the 2-week placebo run-in period (see below), patients had to have had an average frequency of ≥ 8 voids/24 h and have experienced at least three episodes of urgency and/or three episodes of incontinence during the 3-day voiding diary period

18歳以上で、3か月以上の膀胱刺激症状 (頻尿、尿失禁、尿意切迫感)があり、3日間の排尿日記にて、1日8回以上の排尿や、最低3回の尿意切迫感や尿失禁がある男女



significant BOO, a postvoid residual volume of >200 mL, incontinence for which stress was

determined to be the predominant factor, presence of a neurological cause for detrusor

muscle overactivity, evidence of UTI or bladder stones, previous pelvic irradiation,

or previous or current malignant disease of the pelvic organs, any medical condition

contraindicating the use of antimuscarinic medication (including narrow-angle glaucoma and urinary or gastric retention), nonpharmacological treatment for OAB including electrostimulation therapy or start of a bladder training programme during the 2 weeks before or during the study, diabetic neuropathy, use of drugs intended to treat incontinence, use of any drugs with cholinergic or anticholinergic side-effects, and participation in a clinical trial within 30 days before study entry. Women of childbearing potential who were pregnant or

nursing, intending to become pregnant during the study, or who were not using reliable contraceptive methods, were ineligible.



I & C 

Eligible patients after the run-in period (see above) were randomized equally to 12-week double-blind treatment with either tolterodine 2 mg twice daily, placebo, or solifenacin 5 or 10 mg once daily. To maintain blinding, all patients continued to take medication twice daily (using placebo tablets and capsules as necessary) during the 12-week treatment period

12週の治療に及ぶ、トルテロジン2mg 1日2回群と、ソリフェナシン(ベシケア) 5mgもしくは10mg 群と、プラセボ群に無作為に割り付けた。(盲検化するため、プラセボタブレットを使用し、1日2回内服にした。) 



The primary objective of the present phase 3a  trial was to assess the efficacy of solifenacin 5

and 10 mg once-daily compared with placebo in a large sample of patients with symptoms

of OAB.

Efficacy variables included change from baseline in the mean number of urgency episodes and mean number of all incontinence and urge incontinence episodes. Additional variables included mean number of voids/24 h and changes from baseline in mean voided volume/void.

第一目標は、過活動膀胱患者における、プラセボと比較したソリフェナシン (ベシケア) 5mg , 10mg の有効性 (尿意切迫感の平均回数、切迫性尿失禁や全ての尿失禁の平均回数、平均尿量)


The secondary objectives were to assess the safety and tolerability of solifenacin 5 and 10 mg once daily, and to compare the efficacy and safety of solifenacin with tolterodine 2 mg twice daily.

第二目標は、ソリフェナシン5mg, 10mgとトルテロジン2mg (2回/日)を比較した、安全性と忍容性について



This multicentre, randomized, double-blind, tolterodine- and placebo-controlled phase 3a

trial was conducted internationally at 98 centres



A③ 患者はそれぞれの治療群にどのように割り付けられたか?

the four groups were well balanced for all demographic characteristics

Table 1. 参照。4つの治療群の人種別の特徴では、均等に分かれている

The mean number of voids/24 h was 12.08–12.32 and was similar

The mean time from the start of symptoms was 57.4–72.6 months.




Double blind であるが詳細な記載なし







(About a third of patients had received previous drug treatment for OAB)




a power of 90%, 190 evaluable patients per treatment arm were required.

90%の検出力では、各治療群で190人必要 → 十分足りている


B⑧a 結果はどのように示されたか? b 有意差はあるか?
urgency episodes/24 h; compared with the change in the placebo group (-33%), there was a small, statistically insignificant decrease in patients treated with tolterodine (-38%; P= 0.0511) and a statistically significant decrease in those treated with solifenacin 5 mg (-52%) and 10 mg once daily (-55%; both P< 0.001).

1日の尿意切迫感の回数は、プラセボ群で33%減少し、トルテロジン群で統計学的な有意差はないが38%減少し、ソリフェナシン5mgでは52%, 10mgでは55%、有意差をもって減少した。


the change in the mean number of urge incontinence and all incontinence episodes per 24 h; compared with changes in the placebo group (-0.62 episodes/24 h) there were statistically insignificant decreases in both urge and general incontinence with tolterodine. There were statistically significant decreases in the number of urge incontinence episodes in

patients treated with solifenacin 5 mg (-1.41, P= 0.002) and 10 mg (-1.36, P= 0.0028).



Solifenacin also produced statistically significant reductions in all incontinence episodes (5 mg, -1.42,P=.008; and 10 mg, -1.45, P= 0.0038).



the change in mean number of voids/24 h and the percentage change from baseline in each of the four treatment groups. Compared with the change in the placebo group (1.20, -8%), each of the three active treatments was associated with a statistically significant reduction in the mean number of daily voids.



Change from baseline in mean volume voided/void is also shown in Table 2;

compared with the change in the placebo group (7.4 mL) there were statistically significant increases of 24.4 mL (+20.3%) with tolterodine 2 mg twice daily 32.9 mL (+25.1%) with solifenacin 5 mg once daily, and 39.2 mL (+29.0%; all P < 0.001) with solifenacin 10 mg once daily.

平均尿量の変化は、プラセボ群(7.4ml) と比較して、トルテロジン群で24.4ml (+20.3%)、ソリフェナシン5mg群で32.9ml (+25.1%)、10mg群で39.2ml (+29%)と優位に増加した。

c 副作用は 

the incidence of dry mouth was lowest in patients treated with solifenacin 5 mg (14%) and most of these cases (80%) were mild. Constipation, predominantly mild or moderate in all groups,

was reported in 7.2% and 7.8% of patients treated with solifenacin 5 and 10 mg,

respectively, in 2.6% of patients treated with tolterodine and in 1.9% of placebo patients. Blurred vision (mild in most cases) was reported in 3.6% of patients receiving solifenacin 5 mg, 5.6% receiving solifenacin 10 mg, 1.5% receiving tolterodine and 2.6% receiving placebo.


便秘はすべての群で、mild からmoderateであり、ソリフェナシン5mg群で7.2%、10mg群で7.8%、トルテロジン群で2.6%、プラセボ群で1.9%であった。目のかすみはたいていのケースでmildであったが、ソリフェナシン5mg群で3.6%、10mg群で5.6%、トルテロジン群で1.5%、プラセボ群で2.6%であった。









Up to Dateでも、筋トレや生活指導でも改善しない場合の薬物療法としては抗コリン薬が推奨されている。

ただ、下記のsystematic reviewでも効果はあるが限定的と記載。

Benefits and harms of pharmacologic treatment for urinary incontinence in women: a systematic review. - PubMed - NCBI