HALT Progression of Polycystic Kidney Disease Study A
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 558
- 试验地点
- 7
- 主要终点
- Study A: Percent Annual Change in Total Kidney Volume
研究概览
简要总结
The efficacy of interruption of the renin-angiotensin-aldosterone system (RAAS) on the progression of cystic disease and on the decline in renal function in autosomal dominant kidney disease (ADPKD) will be assessed in two multicenter randomized clinical trials targeting different levels of kidney function: 1) early disease defined by GFR >60 mL/min/1.73 m2 (Study A); and 2) moderately advanced disease defined by GFR 25-60 mL/min/1.73 m2 (Study B; NCT01885559). Participants will be recruited and enrolled, either to Study A or B, over the first three years. Participants enrolled in Study A will be followed for at least 5 years, while those enrolled in Study B will be followed for five-to-eight years, with the average length of follow-up being six and a half years. The two concurrent randomized clinical trials differ by eligibility criteria, interventions and outcomes to be studied.
详细描述
* Specific Aims of Study A
To study the efficacy of angiotensin-converting-enzyme inhibitor (ACE-I) and angiotensin-receptor blockade (ARB) combination therapy as compared to ACE-I monotherapy and usual vs. low blood pressure targets on the percent change in kidney volume in participants with preserved renal function (GFR >60 mL/min/1.73m2)and high-normal blood pressure or hypertension (>130/80 mm Hg).
* Hypotheses to be tested in Study A
In ADPKD individuals with hypertension or high-normal blood pressure and relatively preserved renal function (GFR >60 mL/min/1.73 m2), multi-level blockade of the RAAS using ACE-I/ARB combination therapy will delay progression of cystic disease as compared to ACE-I monotherapy, and a low blood pressure goal will delay progression as compared with standard control.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 15 Years 至 64 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of ADPKD.
- •Age 15-49 (Study A); Age 18-64 (Study B).
- •GFR >60 mL/min/1.73 m2 (Study A); GFR 25-60 mL/min/1.73 m2 (Study B).
- •BP ≥130/80 or receiving treatment for hypertension.
- •Informed Consent.
排除标准
- •Pregnant/intention to become pregnant in 4-6 yrs.
- •Documented renal vascular disease.
- •Spot urine albumin-to-creatinine ratio of >0.5 (Study A) or ≥1.0 (Study B) and/or findings suggestive of kidney disease other than ADPKD.
- •Diabetes requiring insulin or oral hypoglycemic agents / fasting serum glucose of >126 mg/dl / random non-fasting glucose of >200 mg/dl.
- •Serum potassium >5.5 milliequivalent per liter (mEq/L) for participants currently on ACE-I or ARB; >5.0 mEq/L for participants not currently on ACE-I or ARB.
- •History of angioneurotic edema or other absolute contraindication for ACE-I or ARB. Intolerable cough associated with ACE-I is defined as a cough developing within six months of initiation of ACE-I in the absence of other causes and resolving upon discontinuation of the ACE-I.
- •Indication (other than hypertension) for β-blocker or calcium channel blocker therapy (e.g. angina, past myocardial infarction, arrhythmia), unless approved by the site principal investigator. (PI may choose to accept an individual who is on only a small dose of one of these agents and would otherwise be eligible.)
- •Systemic illness necessitating nonsteroidal antiinflammatory drugs (NSAIDs), immunosuppressant or immunomodulatory medications.
- •Systemic illness with renal involvement.
- •Hospitalized for acute illness in past 2 months.
- •Life expectancy <2 years.
- •History of non-compliance.
- •Unclipped cerebral aneurysm >7mm diameter.
- •Creatine supplements within 3 months of screening visit.
- •Congenital absence of a kidney (also total nephrectomy for Study B).
- •Known allergy to sorbitol or sodium polystyrene sulfonate.
- •Exclusions specific to magnetic resonance imaging (Study A).
研究组 & 干预措施
Study A, Arm 1
Lisinopril + Telmisartan (ACE-I + ARB) and standard blood pressure control of 120-130/70-80 mm Hg
干预措施: Lisinopril (Drug)
Study A, Arm 1
Lisinopril + Telmisartan (ACE-I + ARB) and standard blood pressure control of 120-130/70-80 mm Hg
干预措施: Telmisartan (Drug)
Study A, Arm 1
Lisinopril + Telmisartan (ACE-I + ARB) and standard blood pressure control of 120-130/70-80 mm Hg
干预措施: Standard Blood Pressure Control (Other)
Study A, Arm 2
Lisinopril + Telmisartan (ACE-I + ARB) and low blood pressure control of 95-110/60-75 mm Hg
干预措施: Lisinopril (Drug)
Study A, Arm 2
Lisinopril + Telmisartan (ACE-I + ARB) and low blood pressure control of 95-110/60-75 mm Hg
干预措施: Telmisartan (Drug)
Study A, Arm 2
Lisinopril + Telmisartan (ACE-I + ARB) and low blood pressure control of 95-110/60-75 mm Hg
干预措施: Low Blood Pressure Control (Other)
Study A, Arm 3
Lisinopril + Placebo (ACE-I + Placebo) and standard blood pressure control of 120-130/70-80 mm Hg
干预措施: Lisinopril (Drug)
Study A, Arm 3
Lisinopril + Placebo (ACE-I + Placebo) and standard blood pressure control of 120-130/70-80 mm Hg
干预措施: Placebo (Drug)
Study A, Arm 3
Lisinopril + Placebo (ACE-I + Placebo) and standard blood pressure control of 120-130/70-80 mm Hg
干预措施: Standard Blood Pressure Control (Other)
Study A, Arm 4
Lisinopril + Placebo (ACE-I + Placebo) and low blood pressure control of 95-110/60-75 mm Hg
干预措施: Lisinopril (Drug)
Study A, Arm 4
Lisinopril + Placebo (ACE-I + Placebo) and low blood pressure control of 95-110/60-75 mm Hg
干预措施: Placebo (Drug)
Study A, Arm 4
Lisinopril + Placebo (ACE-I + Placebo) and low blood pressure control of 95-110/60-75 mm Hg
干预措施: Low Blood Pressure Control (Other)
结局指标
主要结局
Study A: Percent Annual Change in Total Kidney Volume
时间窗: Baseline and 2-, 4- and 5-year follow-up
Annual percentage change in total kidney volume as assessed by abdominal magnetic resonance imaging (MRI) at baseline, 2 years, 4 years, and 5 years follow-up.
次要结局
- All-Cause Hospitalizations(Up to 96 months)
- Quality of Life Mental Component Summary(baseline, 12, 24, 36, 48, 60, 72, 84, and 96 months (assessed annually))
- Aldosterone(Up to 96 months (assessed annually))
- Quality of Life Physical Component Summary(baseline, 12, 24, 36, 48, 60, 72, 84, and 96 months (assessed annually))
- Kidney Function (eGFR)(Up to 96 months (6 month assessments))
- Left Ventricular Mass Index(0, 24 months, 48 months, 60 months)
- Albuminuria(Up to 96 months (assessed annually))
- Renal Blood Flow(0, 24 months, 48 months, 60 months)