HALT Progression of Polycystic Kidney Disease Study B
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 486
- 试验地点
- 7
- 主要终点
- Number of Participants With 50% Reduction of Baseline eGFR, End Stage Renal Disease (ESRD, Initiation of Dialysis or Preemptive Transplant), or Death.
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 simultaneous 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). Participants will be recruited and enrolled, either to Study A or B, over the first three years. Participants 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.
Combination therapy will use angiotensin-converting-enzyme inhibitor (ACE-I) and an angiotensin-receptor blocker (ARB). Monotherapy will use ACE-I alone.
详细描述
* Specific Aim of Study B
To study the effects of ACE-I/ARB combination therapy as compared to ACE-I monotherapy in the setting of standard blood pressure control (110-130/80 mm Hg) on the time to a 50% reduction of baseline estimated Glomerular Filtration Rate (eGFR), end-state renal disease (ESRD) or death, in hypertensive individuals with moderate renal insufficiency (GFR 25-60 mL/min/1.73m2).
* Hypothesis to be tested in Study B
In hypertensive ADPKD individuals with moderate renal insufficiency (GFR 25-60 mL/min/1.73 m2), intensive blockade of the RAAS using combination ACE-I/ARB therapy will slow the decline in kidney function over ACE-I monotherapy, independent of standard blood pressure control (110-130/80 mm Hg).
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
- 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 (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 (MR) imaging (Study A).
研究组 & 干预措施
ACE-I + placebo
Monotherapy of lisinopril and placebo. Standard blood pressure control of 110-130/80 mm Hg
干预措施: Lisinopril (Drug)
ACE-I + placebo
Monotherapy of lisinopril and placebo. Standard blood pressure control of 110-130/80 mm Hg
干预措施: Placebo (Drug)
ACE-I + ARB
Dual therapy of lisinopril and telmisartan treatments. Standard blood pressure control of 110-130/80 mm Hg.
干预措施: Lisinopril (Drug)
ACE-I + ARB
Dual therapy of lisinopril and telmisartan treatments. Standard blood pressure control of 110-130/80 mm Hg.
干预措施: Telmisartan (Drug)
结局指标
主要结局
Number of Participants With 50% Reduction of Baseline eGFR, End Stage Renal Disease (ESRD, Initiation of Dialysis or Preemptive Transplant), or Death.
时间窗: Patients followed for 5-8 years with average of 6.5 years follow up
次要结局
- Hospitalizations(up to 8 years)
- Cardiovascular Hospitalizations(up to 8 years)
- Quality of Life Physical Component Summary(up to 8 years (annually assessed))
- Back or Flank Pain(48 months)
- Aldosterone(up at 8 years (annually assessed))
- Quality of Life Mental Component Summary(up to 8 years (annually assessed))
- Albuminuria(up to 8 years (annually assessed))