HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 25
- 主要终点
- Changes in kidney function decline
研究概览
简要总结
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive formation of renal cysts which ultimately lead to a loss of renal function.
Tolvaptan (a V2R antagonist) is currently the only effective treatment for preserving renal function in ADPKD. However, side-effects such as polyuria limit its tolerability and thereby the therapeutic potential. This study will test whether co-administration with hydochlorothiazide can improve V2RA efficacy (slowing kidney function decline) and tolerability (quality of life) in ADPKD. Approximately 300 patients will be enrolled.
详细描述
Aims: The main objectives of the current study are to prospectively test whether HCT co-treatment can improve V2RA efficacy (slowing kidney function decline) and tolerability (quality of life) in PKD.
Study design: Investigator driven randomized placebo-controlled multicenter trial
Study population: 300 ADPKD patients of ≥18 years, with an eGFR of > 25 mL/min/1.73m2, on stable treatment with the highest tolerated dose of V2RA
Intervention: Oral HCT 25 mg once daily or matching placebo for a total of 156 weeks. The randomization ratio will be 1:1.
Study visit schedule: study measurements will be performed during 12-weekly visits (which is routine care for V2RA treated patients), except for one additional study visit (or telephone call) 2 weeks after the start of treatment
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
- Quadruple (Participant, Care Provider, Investigator, 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
- •ADPKD diagnosis (modified Ravine criteria)
- •≥18 years old
- •eGFR > 25 mL/min/1.73m2
- •On stable treatment with the highest tolerated dose of V2RA for a minimum of 3 months
排除标准
- •Known intolerance to hydrochlorothiazide
- •Use of any diuretic
- •Orthostatic hypotension complaints or blood pressure <105/65mmHg during screening visit
- •Uncontrolled hypertension (blood pressure >160/100mmHg)
- •Hypokalemia (<3.5 mmol/L)
- •History of active gout on maintenance preventive treatment for gout (allopurinol, desuric and/or colchicine), defined as ≥2 episodes during the last year
- •History of skin cancer (basal cell, squamous cell and melanoma)
研究组 & 干预措施
Placebo
Matching oral placebo, once daily, for a total of 156 weeks. The placebo is inert.
干预措施: Placebo (Drug)
Hydrochlorothiazide
Oral hydrochlorothiazide 25mg, once daily, for a total of 156 weeks
干预措施: Hydrochlorothiazide 25 mg (Drug)
结局指标
主要结局
Changes in kidney function decline
时间窗: 156 weeks
The primary outcome is the change in kidney function decline (assessed as eGFR slope, in ml/min/1.73 m2 per year), calculated with linear mixed models, using all available creatinine values from week 12 until end of treatment between the tolvaptan/placebo and tolvaptan/HCT group.
次要结局
- Quality of life, assessed by the SF-12 questionnaire(156 weeks)
- Quality of life, assessed by the EQ-5D questionnaire(156 weeks)
- Change in V2RA dose(168 weeks)
- Change in V2RA discontinuation rate(168 weeks)
- Changes in serum sodium concentration(168 weeks)
- Changes in eGFR from baseline compared to end of study (12 weeks after End of Treatment)(168 weeks)
- Incidence of 30% decrease in eGFR, end stage kidney disease (EKSD) or renal death(168 weeks)
- Changes in 24-hour urine volume(156 weeks)
- Quality of life, assessed by the TIPS questionnaire(156 weeks)
- Quality of life, assessed by the ADPKD-UIS questionnaire(156 weeks)
- Changes in serum potassium concentration(168 weeks)
- Changes in plasma serum calcium concentration(168 weeks)
- Changes in serum phosphate concentration(168 weeks)
- Incidence of (serious) adverse events(168 weeks)
研究者
Ron Gansevoort
Prof. dr.
University Medical Center Groningen