Incobotulinumtoxin Versus Onabotulinumtoxin in the Treatment of Patients With Overactive Bladder Syndrome
试验速览
- 阶段
- 3 期
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Change from baseline in the frequency of urinary incontinence episodes.
研究概览
简要总结
The aim of the original study was to compare Incobot/A versus Onabot/A in order to evaluate if the differences in the pharmacologic formulations between the two drugs could affect their efficacy and safety in the treatment of neurogenic overactive bladder (OAB).
In the original study protocol two different dosages for either Incobot/A and Onabot/A (200 U and 100 U) were considered, to treat patients with neurogenic detrusor overactivity incontinence performing intermittent catheterization (IC) with higher dosages and those able to void spontaneously with lower dosage, with the resulting four treatment groups. For such a study, a very large sample of participants should have been treated and followed up, to have adequate power to demonstrate the hypothesis. At the end of last February 2020, we had to temporarily stop all the clinical activities related to the study and patients' recruitment, due to the occurrence of Sars-Cov-2 pandemic in our Country. At that point, a non-inferiority study seemed to be possible and adequate, and we adapted the protocol accordingly. In addition, on the basis of previously published information, we could hypothesize that the new drug (Incobot/A) would have had at least a roughly similar effect to the control drug (Onabot/A). In order to perform a non-inferiority study, the power and sample size analysis have been re-planned.
Thus, we perform a not planned interim analysis to show the preliminary results of an ongoing, non-inferiority trial in which patients' recruitment temporarily stopped due to incontrollable external factors. The present study will be aimed to assess the non-inferiority of Incobot/A compared to Onabot/A on the efficacy and safety parameters, in the treatment of patients with refractory NDOI performing IC, who are randomized to receive 200 U of Incobot/A or Onabot/A intradetrusor injections and who are followed up to 12 wks after treatment
详细描述
This is a pilot, prospective, randomized, double blinded, multicentre, clinical trial. After giving a written informed consent, all the patients will be randomized into two groups: Group 1, including patients who will be treated with the Incobot/A and Group 2, including patients who will be treated with Onabot/A. The randomization process will be made by a computerized system. Enrolling period: September 2018- April 2020.
Inclusion criteria:
- patients (males and females) with neurogenic urge urinary incontinence (UUI) (with urgency, increase in day- time and night- time urinary frequency) and with urodynamic diagnosis of detrusor overactivity (DO);
- 18- 80 years;
- women of childbearing age, who use a reliable method of contraception throughout the study period (a pregnancy test must be performed during enrolment in the study);
- spinal cord injury at or below T1, diagnosed at least 6 months before the screening in case of a vesico-sphincter dysfunction due to spinal cord injury;
- EDSS score ≤ 6, in MS patients;
- patients refractory to anticholinergic therapy (≥ 1 anticholinergic agent)
- application of intermittent catheterizations to empty the bladder. In the case of spontaneous micturition, the patients should agree for the use of intermittent catheterizations, in case this will be necessary after treatment with the detrusor injection of botulinumtoxin A.
Urodynamic characteristics:
urodynamic diagnosis of DO, refractory to standard anticholinergics and naïve to intradetrusor injection of onabotulinumtoxin A.
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
- Double (Participant, Investigator)
盲法说明
Partecipants, investigators and outcomes assessor
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patients (males and females) with neurogenic urge urinary incontinence (UUI) (with urgency, increase in day- time and night- time urinary frequency) and with urodynamic diagnosis of DO;
- •18- 80 years;
- •women of childbearing age, who use a reliable method of contraception throughout the study period (a pregnancy test must be performed during enrolment in the study);
- •spinal cord injury at or below T1, diagnosed at least 6 months before the screening in case of a vesico-sphincter dysfunction due to spinal cord injury;
- •EDSS score ≤ 6, in MS patients;
- •patients refractory to anticholinergic therapy (≥ 1 anticholinergic agent)
- •application of intermittent catheterizations to empty the bladder. In the case of spontaneous micturition, the patients should agree for the use of intermittent catheterizations, in case this will be necessary after treatment with the detrusor injection of botulinumtoxin A.
排除标准
- •recurring urinary tract infections (UTIs) (≥ 4 episodes/year);
- •spinal cord injuries above T1;
- •MS patients: EDSS score ≥ 6;
- •patients who won't or can't perform intermittent catheterization;
- •pregnancy or breast- feeding, if female patients;
- •post- void residual volume (PRV) > 150 ml, in the case of spontaneous micturition;
- •hypersensitivity to the active substance or to any of the excipients (listed in section 6.1 of RCP);
- •generalized diseases of muscular activity (e.g. myasthenia gravis, Lambert-Eaton syndrome);
- •presence of infection or inflammation at the injection site;
- •patients with acute urinary retention at the time of treatment, not routinely subjected to catheterization;
- •men with overactive bladder and signs or symptoms of urinary obstruction should not be treated;
- •documented or suspected active malignant neoplasia or previous history, within 2 years prior to screening;
- •patients who must or want to continue taking illegal drugs or drugs that may interfere with the proper conduct of the study;
- •chronic abuse of alcohol or drugs or any condition that in the opinion of the investigator doctor makes an unreliable subject in correctly completing the study procedures;
- •any other clinical condition that would endanger the safety of patients in participating in the study or that could prevent the subjects from adhering to the protocol.
研究组 & 干预措施
Incobot/A 100 U
Incobot/A 100 U diluted in 10 ml of sodium chloride solution 0.9% by endoscopic detrusor injections (20 injections, 0.5 ml of solution for each injection) will be administered in patients able to perform spontaneous micturitions
干预措施: IncobotulinumtoxinA 100 UNT Injection [Xeomin] (Drug)
Incobot/A 200 U
Incobot/A 200 U diluted in 30 ml of sodium chloride solution 0.9% by endoscopic detrusor injections (30 injections, 1 ml of solution for each injection) will be administered in patients performin intermittent catheterization.
干预措施: IncobotulinumtoxinA 100 UNT Injection [Xeomin] (Drug)
Onabot/A 100 U
Onabot/A 100 U diluted in 10 ml of sodium chloride solution 0.9% by endoscopic detrusor injections (20 injections, 0.5 ml of solution for each injection) will be administered in patients able to perform spontaneous micturitions
干预措施: OnabotulinumtoxinA 100 UNT [Botox] (Drug)
Onabot/A 200 U
Onabot/A 200 U diluted in 30 ml of sodium chloride solution 0.9% by endoscopic detrusor injections (30 injections, 1 ml of solution for each injection) will be administered to patients performing intermittent catheterization
干预措施: OnabotulinumtoxinA 100 UNT [Botox] (Drug)
结局指标
主要结局
Change from baseline in the frequency of urinary incontinence episodes.
时间窗: 24 weeks
change from baseline in the daily frequency of urinary incontinence episodes, as assessed by the 3-day voiding diary.
Evaluation of frequency of urinary tract infections in both arms of treatment.
时间窗: 2, 12, 24 weeks
Measurement of eventual differencies between the two arms of treatment in the frequency of urinary tract infections at 2, 12 and 24 weeks after treatment
次要结局
- Change from baseline in Incontinence Quality of Life (I-QoL) questionnaire total score.(2, 12, 24 weeks)
- Change from baseline in urodynamic parameters.(24 weeks)
- Recording of the adverse events.(2, 12, 24 weeks)
研究者
Antonella Giannantoni
PA
University Of Perugia