Efficacy of Solifenacin, Mirabegron and Combination Therapy in Children With Overactive Bladder and Daytime Urinary Incontinence (BeDry)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 236
- 试验地点
- 10
- 主要终点
- Treatment response
研究概览
简要总结
The primary objective is to evaluate if (1) combination therapy of solifenacin and mirabegron in low doses is superior to monotherapy of solifenacin in high dose and if (2) combination therapy of mirabegron and solifenacin in low doses is superior to monotherapy of mirabegron in high dose in treatment of daytime urinary incontinence among children aged 5 to 14 years who are none complete responders to respectively monotherapy of solifenacin in low dose or monotherapy of mirabegron in low dose.
In total, 236 children diagnosed with daytime urinary incontinence will be randomized 1:1:1:1 to one of four treatment groups. Total pharmacological treatment period will be 18 weeks.
详细描述
Background: According to International Children's Continence Society, first-line treatment of children with daytime urinary incontinence is standard urotherapy, eventually followed by pharmacotherapy of anticholinergics. The effect of medical treatment is sparsely investigated and primarily in non-randomized trials.
Objectives: The primary objective is to evaluate if (1) combination therapy of solifenacin and mirabegron in low doses is superior to monotherapy of solifenacin in high dose and if (2) combination therapy of mirabegron and solifenacin in low doses is superior to monotherapy of mirabegron in high dose in treatment of daytime urinary incontinence among children aged 5 to 14 years who are none complete responders to respectively monotherapy of solifenacin in low dose or monotherapy of mirabegron in low dose.
The secondary objective is to evaluate the treatment response of combination therapy of solifenacin and mirabegron in low doses, monotherapy in high dose and monotherapy in low doses as supplementary comparisons. Additionally, the secondary objective is to evaluate side effects, safety, and tolerability of the medical treatment as well as the effect of treatment on well-being and quality of life.
Study design: The BeDry study is designed as a multicenter, randomized, single-blinded, controlled clinical trial. Included children will be randomized 1:1:1:1 to one of four treatment groups. Children aged 5-14 years diagnosed with daytime urinary incontinence refractory to standard urotherapy will be randomized. Initially two groups will receive solifenacin 5 mg and two groups will receive mirabegron 25 mg. After 6 weeks, non-complete respondsers will receive add-on treatment according to their primary randomization group; group 1A will reviece solifenacin 5 mg and add-on solifenacin 5 mg, group 1B will receive solifenacin 5 mg and add-on mirabegron 25 mg, group 2A will receive mirabegron 25 mg and add-on mirabegron 25 mg, group 2B will receive mirabegron 25 mg and add-on solifenacin 5 mg. Total treatment period will be 18 weeks. The primary endpoint measure is treatment response assessed by change from visit 2 to end of study, according to number of wet days pr. 7 days by DryPie.
Perspectives: The trial has the potential to optimize medical treatment of children with daytime urinary incontinence, to shorten the treatment period, diminish side effects and minimized unnecessary medical expenses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
盲法说明
The study is single-blinded, and the study subject will receive medication delivered from the study site. The investigator does not know which treatment the individual participant receives. Participants will be informed that they are not allowed to reveal the blinded investigator the study medication, and an unblinded nurse will guide and answer questions to participants in case of dose titration.
入排标准
- 年龄范围
- 5 Years 至 14 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participants custody holder(s) must voluntarily sign and date an informed consent prior to initiation of any study specific procedures.
- •Age 5 to 14 years (inclusive) at the time of inclusion.
- •Overactive bladder as per International Children's Continence Society criteria
- •At least 2 daytime urinary incontinence episodes per week
- •Inadequate effect of at least 4 weeks urotherapy (non-pharmacological treatment)
- •No previous treatment with solifenacin, mirabegron or bladder/sphincter botulinum toxin injections
- •No current constipation as per ROME IV criteria or fecal incontinence (laxative treatment is accepted)
- •Per investigator's judgment, the participant can swallow or can learn to swallow study medication
排除标准
- •Inability of the patent(s) or legal guardian(s) to understand the Danish written and oral information
- •Known or suspected hypersensitivity to study medication
- •Any contraindication to the use of the study medication
- •Known urogenital anatomical abnormalities affecting lower urinary tract function
- •Known kidney or bladder stones
- •Known diabetes insipidus
- •Ongoing symptomatic urinary tract infection
- •Recurrent urinary tract infection or ongoing prophylactic antibiotic treatment
- •Known QTc prolongation, QTc >460 ms, or risk of QTc prolongation (hypokalaemia, exercise-induced syncope, or familial long QT syndrome)
- •Other significant electrocardiogram abnormalities
- •Known hypertension
- •≤3 daily voiding, evaluated by 48-hour frequency-volume chart
- •Uroflowmetry suggestive of other pathology than overactive bladder (staccato-shaped, interrupted-shaped, or plateau-shaped curve)
- •Post-void residual >50 ml after double voiding
- •Dipstick haematuria (≥2+ erythrocytes) or macroscopic haematuria
- •Pregnancy or breastfeeding
- •Female subjects of childbearing potential
- •Ongoing constipation according to Rome IV-criteria which is intractable to medication or fecal incontinence
- •Inability to swallow study medication
- •Use of any medication during study period, except permitted medication
研究组 & 干预措施
Solifenacin 5 mg + add-on solifenacin 5 mg
Group 1A: Solifenacin 5 mg for 6 weeks, and if non-complete response after 6 weeks add-on solifenacin 5 mg for 12 weeks.
干预措施: Solifenacin (Drug)
Mirabegron 25 mg + add-on solifenacin 5 mg
Group 2B: Mirabegron 25 mg for 6 weeks, and if non-complete response after 6 weeks add-on solifenacin 5 mg for 12 weeks.
干预措施: Solifenacin (Drug)
Mirabegron 25 mg + ad-on mirabegron 25 mg
Group 2A: Mirabegron 25 mg for 6 weeks, and if non-complete response after 6 weeks add-on mirabegron 25 mg for 12 weeks.
干预措施: Mirabegron (Drug)
Mirabegron 25 mg + add-on solifenacin 5 mg
Group 2B: Mirabegron 25 mg for 6 weeks, and if non-complete response after 6 weeks add-on solifenacin 5 mg for 12 weeks.
干预措施: Mirabegron (Drug)
Solifenacin 5 mg + add-on mirabegron 25 mg
Group 1B: Solifenacin 5 mg for 6 weeks, and if non-complete response after 6 weeks add-on mirabegron 25 mg for 12 weeks.
干预措施: Solifenacin (Drug)
Solifenacin 5 mg + add-on mirabegron 25 mg
Group 1B: Solifenacin 5 mg for 6 weeks, and if non-complete response after 6 weeks add-on mirabegron 25 mg for 12 weeks.
干预措施: Mirabegron (Drug)
结局指标
主要结局
Treatment response
时间窗: From study week 6 and through study completion, an average of 18 weeks in total
Assesed by change in number of wetdays pr. 7 days by DryPie
次要结局
- Maximum voided volume (ml)(From date of randomization until study completion, an average of 18 weeks in total)
- Average voided volume (ml)(From date of randomization until study completion, an average of 18 weeks in total)
- Age standardized maximum voided volume (ml)(From date of randomization until study completion, an average of 18 weeks in total)
- Pediatric incontinence questionnaire total score(From date of randomization until study completion, an average of 18 weeks in total)
- WHO-5 total score(From date of randomization until study completion, an average of 18 weeks in total)
- Miction frequency(From date of randomization until study completion, an average of 18 weeks in total)
- Treatment response(From date of randomization until study completion, an average of 18 weeks in total)
- Inconcintnence severity score(From date of randomization until study completion, an average of 18 weeks in total)
- Urge severity(From date of randomization until study completion, an average of 18 weeks in total)