Prevention and Management of Intravesical BCG-related Lower Urinary Tract Symptoms With Prophylactic Pentosan Polysulphate in Patients With Non-Muscle-Invasive Bladder Cancer: A Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Determine the efficacy (Urgency episodes assessed by bladder diary) a of co-administration of Pentosan Polysulphate in preventing BCG-related LUTS in adult subjects with a diagnosis of NMIBC.
研究概览
简要总结
Common local side effects are generally seen during induction and during the first 6 months of BCG maintenance. BCG-related cystitis is frequent and unavoidable. Furthermore, repeated BCG instillation increases the incidence and severity of irritative bladder symptoms. Several methods attempted to reduce the intensity and frequency of BCG- related lower urinary tract symptoms (LUTS), such as, administration of anti-tuberculosis drug isoniazid or oral antibiotic ofloxacin or by reducing the BCG dose, but without any encouraging results. Local side effects requiring cessation of treatment are seen more frequently in the first year of therapy, preventing patients from receiving their BCG maintenance regimen.
Pentosan Polysulphate (PPS), is an oral medication with unique analgesic properties used to relieve bladder pain and discomfort related to other conditions, has been investigated in a small study with encouraging result in this patient population. This suggest that PPS is well tolerated and effective at decreasing BCG-related LUTS.
The purpose of this study is first to investigate the efficacy of co-administration of Pentosan Polysulphate to prevent these adverse events and the impact of this intervention on quality of life. The second goal is to determine which patients are more vulnerable to develop BCG- related lower urinary tract symptoms (LUTS), based on clinical assessment, demographics data, voiding parameters, and urinary inflammatory markers, and then to assess the effectiveness of BCG therapy following co-administration of ELMIRON.
详细描述
Study purpose and rationale:
BCG-related LUTS is a condition which can have a significant negative impact on the psychological well-being, social functioning, and overall quality of life of bladder cancer patients. Clinical studies have demonstrated effects of PPS on damaged urothelium in the bladder, which is a key feature for diminishing BCG local side effects. The "dual action" protective effect on bladder epithelium and replacing the mucus in the glycosaminoglycan layer of damaged urothelium provides a scientific rationale to evaluate whether PPS treatment may be a preventive option for NMIBC patients treated with BCG.
It is therefore important to find a treatment strategy to control the BCG-related LUTS so that candidate patients do not lose the benefit of BCG treatment while maintaining its efficacy and ensuring optimal outcomes. This study will identify the patients that are more vulnerable to develop these side effects and determine the efficacy of PPS to diminish BCG- related lower urinary tract symptoms (LUTS) and associated impact on quality of life.
Sample Size:
For the first aim, power analysis was estimated using a One-way (ANOVA) hypothesis test with a type 1 error of 5%, 80% power, and 20% dropout rate. It was calculated based on the ICIQ-LUTSqol expected values. The baseline mean ICIQ-LUTSqol score used was 33.1 and SD of 7.3, the outcome ICIQ-LUTSqol score mean used 28.48, with a SD of 4.95, which is the minimally important difference of 3.7124. The investigator calculate a number of 30 patients per group, for a total sample size of 60. (Calculated by pass program v 15.0.03)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients aged 18 to 85 will be eligible for inclusion in this study if all of the following criteria apply:
- •Willing to provide written informed consent
- •Confirmed diagnosis (biopsy-proven) of intermediate- and high-risk NMIBC
- •Two to four weeks following complete tumor resection
- •Candidate for BCG induction therapy based on CUA clinical guidelines
- •Subjects must not be pregnant, lactating, or actively trying to become pregnant, Subjects who are premenopausal and of childbearing potential must have a negative pregnancy test at Screening (serum) and at Day 0 (urine) and must use a medically acceptable and effective method of birth control for the duration of the study, which can include:
- •Having a male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject
- •Use of double-barrier methods of contraception; condoms with the use of caps (with spermicide) and intra-uterine devices are acceptable
- •Use of hormonal contraceptives (oral, depots, patches, etc.) with double-barrier methods of contraception as outline above
- •True abstinence: When this is in line with the preferred and usual lifestyle of the subject (period abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
排除标准
- •Contraindications to BCG therapy
- •Solitary tumors except pT1 high grade
- •Tumor stage ≥ T2
- •Previous BCG or chemotherapy instillation
- •Carcinoma in situ and variant histology of urothelial carcinoma
- •Subjects with concurrent (at Screening), urinary tract infections (positive dipstick for urinary tract infection and abnormal microscopic evaluation, signs and symptoms)
- •Unevaluated urinary retention, Post void residual (PVR) urine volume > 150 ml
- •Diagnosis of dementia
- •Any concurrent condition or any clinically significant abnormality on the screening physical examination, laboratory tests, which, in the opinion of the Investigator, may affect the interpretation of efficacy or safety data, or which otherwise contraindicates participation in a clinical study with PPS.
- •Hypersensitivity to PPS or any of its ingredients
- •History of clinically significant drug hypersensitivity.
- •Clinically significant or unstable, endocrine, hepatic, renal, immunologic, or heart disease
- •Patients at increased hemorrhagic risk due to unstable disease course (ulcerative GI lesions, aneurysms, internal or external hemorrhoids, thrombocytopenia, hemophilia, polyps or diverticulae).
- •Use of any pharmacologic agent used to treat symptoms of LUTS
- •Participation in a clinical study within the month prior to screening, or exposure to an investigational drug which has not washed out since the last administration prior to screening
- •In the opinion of the Investigator, is at risk of non-compliance with study procedures, or cannot read, understand, or complete study-related materials, particularly informed consent
- •Participation in any clinical study of an investigational drug that may affect urinary function within 1 months prior to screening
- •Severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73m2)
- •Severe hepatic impairment (Child-Pugh B or greater)
- •You are pregnant or breastfeeding
研究组 & 干预措施
Pentosan Polysulfate Na 100Mg Cap
Drug intervention of Pentosan Polysulfate Na 100Mg Cap (ELMIRON) thrice daily PO for 6 weeks, after meeting the eligibility criteria during the the two-week Screening period.
干预措施: Pentosan Polysulfate Na 100Mg Cap (Drug)
Placebo oral capsule
Participants will receive Placebo oral capsule, similar to (ELMIRON 100mg) thrice daily PO for 6 weeks, , after meeting the eligibility criteria during the the two-week Screening period.
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Determine the efficacy (Urgency episodes assessed by bladder diary) a of co-administration of Pentosan Polysulphate in preventing BCG-related LUTS in adult subjects with a diagnosis of NMIBC.
时间窗: Start of treatment to End of treatment (6weeks)
Primary outcome assessment (change from baseline to end of treatment): -Mean change in number of urgency episodes per 24 hours based on a 3-day bladder diary
Determine the efficacy (Urgency episodes assessed by ICIQ-LUTSqol questionnaire) a of co-administration of Pentosan Polysulphate in preventing BCG-related LUTS in adult subjects with a diagnosis of NMIBC.
时间窗: Start of treatment to End of treatment (6weeks)
Primary outcome assessment (change from baseline to end of treatment): -Mean change in ICIQ-LUTSqol questionnaire score
Determine the efficacy (Urgency episodes assessed by OAB-V8 questionnaire) a of co-administration of Pentosan Polysulphate in preventing BCG-related LUTS in adult subjects with a diagnosis of NMIBC.
时间窗: Start of treatment to End of treatment (6weeks)
Primary outcome assessment (change from baseline to end of treatment): -Mean change in OAB-V8 questionnaire score
Determine the safety (Adverse events or reactions as assessed by CTCAE v5.0) of co-administration of Pentosan Polysulphate in preventing BCG-related LUTS in adult subjects with a diagnosis of NMIBC.
时间窗: Start of treatment to End of treatment (6weeks)
Safety: (Number of participants with treatment-related adverse events as assessed by CTCAE v5.0) -Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 at the End of treatment Visit (week 6)
次要结局
- Efficacy of BCG therapy (cancer recurrence and progression assessed by cystoscopy) following co-administration of Pentosan Polysulphate(12 weeks and 24 weeks)
- Efficacy of BCG therapy (cancer recurrence and progression assessed by urine cytology) following co-administration of Pentosan Polysulphate(12 weeks and 24 weeks)
- Predisposing factors to developing BCG-related LUTS involving secondary analysis of patient's characteristics pre- and post-treatment(Start of treatment to End of treatment (6weeks))
- Predisposing factors to developing BCG-related LUTS evaluated by ELISA quantitative measures of urinary inflammatory markers before and after BCG therapy(Start of treatment to End of treatment (6weeks))
- Health-related quality of life (HRQoL) assessed by ICIQ-LUTSqol questionnaire(Baseline, 6weeks , 12 weeks and 24 weeks)
- Health-related quality of life (HRQoL) assessed by VAS questionnaire(Baseline, 6weeks , 12 weeks and 24 weeks)
研究者
Lysanne Campeau, MDCM, PhD, FRCSC
Assistant Professor
Sir Mortimer B. Davis - Jewish General Hospital