Flexibly adding-on Second Antimuscarinic Agent to the First Antimuscarinics for Refractory Overactive Bladder Syndrome
Condition: Overactive Bladder
MeSH terms: Urinary Bladder, Overactive
Study type: Interventional
Phase: Phase 4

Summary: 
      To investigate if oxybutynin ER adding on antimuscarinics is more effective than
      mono-antimuscarinic treatment for patients with refractory OAB
    

Detailed description: 
      -  Introduction:Overactive bladder (OAB) is a symptom syndrome characterized by urgency
           frequency with or without urgency incontinence. Usually no metabolic or anatomical
           disorders can be found in patients with OAB, and the condition may have a great impact
           on quality of life. Antimuscarinics are the first line treatment and yield a success
           rate of more than 70%. Urothelial dysfunction and abnormalities of sensory receptor
           expression or transmitter release in the suburothelial nerves might contribute to OAB
           which is refractory to antimuscarinics. In patients who failed current antimuscarinic
           treatment, intravesical botulinum toxin A (BoNT-A) injection provides an chance of
           improvement. Previous studies reported success rates of BoNT-A injection for OAB ranged
           from 60 to 80%. Intravesical treatment to inhibit abnormal receptor expression or
           transmitter release in the sensory nerve terminals of the suburothelial space can
           provide good therapeutic effects in the treatment of OAB. However, patients might
           develop large postvoid residual (PVR) and subsequent urinary tract infection (UTI) after
           BoNT-A injections, therefore, this treatment is usually left for patients who are
           refractory to antimuscarinic therapy. However, how to define antimuscarinic refractory
           OAB remains controversial. How many different types of antimuscarinics should be
           prescribed before we call the case failure has not been elucidated. The aim of this
           study is to evaluate the effect of flexibly adding-on oxybutynin ER (5mg QD) in patients
           with OAB who were refractory to monotherapy with the first antimuscarinic agent
           (tolterodine 4mg QD).

        -  Methods: A total of 200 patients with refractory OAB will be included in this
           prospective, open label protocol. Inclusion criteria are persistent OAB symptoms
           (frequency urgency with/without urgency urinary incontinence) after behaviour therapy
           and an optimized dose of one antimuscarinic agent (Tolterodine 4mg) for at least 3
           months. Patients with neurogenic diseases, untreated bladder outlet obstruction,
           recurrent UTI, large PVR (>150ml) will be excluded from this study. Patients will be
           randomized to allocate in the treatment group (receiving tolterodine 4mg QD and
           oxybutynin 5mg to 15mg QD) or control group (tolterodine 4mg QD) in 1:1 ratio based on
           the permuted block randomization code. Oxybutynin ER 5mg to 15 mg once daily will be
           flexibly adding-on from baseline to the third month in the treatment group, depending on
           patient's effectiveness and tolerability to adverse events. At the baseline, 1 and 3
           months after oxybutynin ER adding-on, we will assess the International Prostate Symptom
           Score (IPSS), Overactive Bladder Symptom Score (OABSS), Patient Perception of Bladder
           Condition (PPBC), the Urgency Severity Scale (USS) questionnaires, uroflowmetry and PVR.
           The therapeutic effect will be considered as successful if there was a reduction of PPBC
           of 2 from baseline and a reduction of USS of 1 from baseline, or the USS value is 0 at 3
           months. The adverse events and tolerability of this combined therapy will also be
           assessed.

        -  Expected Results: Compared with baseline, total IPSS, IPSS storage subscore, quality of
           life indexes, OABSS, USS and PPBC will be expected to significantly decrease at 1 and 3
           months. PVR might be increased at 3 months after adding-on treatment. The changes of
           IPSS voiding subscore, peak urinary flow rate and voided volume might be increased or
           comparable to the control group during the follow-up. We expect at least one-third of
           patients can have a successful therapeutic effect without significantly increased
           adverse events. However, the other patients might withdraw from the study due to adverse
           events such as severe dry mouth, constipation, large PVR, UTI, severe difficult
           urination or acute urinary retention.

      Adverse events should be cautiously monitored during the treatment course.
    

Intervention name(s): Detrusitol 4mg QD and Oxybutynin ER 5mg QD; Detrusitol 4mg QD
Intervention type(s): Drug; Drug
Intervention description(s): Study group; Control group
Other intervention name(s): Tolterodine (Detrusitol) 4mg QD; Oxybutynin (Ditropan) ER 5mg QD; Tolterodine (Detrusitol) 4mg QD
Intervention MeSH terms: Mandelic Acids; Tolterodine Tartrate; Oxybutynin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Prospective, open-label study. The overactive bladder patients maintained their previous antimuscarinic medication and we flexibly added on the second antimuscarinic drug (oxybutynin ER 5 mg QD) or not.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Refractory overactive bladder syndrome; Antimuscarinic agent