HALT Progression of Polycystic Kidney Disease Study A
- Conditions
- Kidney, Polycystic
- Interventions
- Drug: PlaceboOther: Low Blood Pressure ControlOther: Standard Blood Pressure Control
- Registration Number
- NCT00283686
- Brief Summary
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.
- Detailed Description
\* 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 558
- 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.
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Study A, Arm 1 Lisinopril Lisinopril + Telmisartan (ACE-I + ARB) and standard blood pressure control of 120-130/70-80 mm Hg Study A, Arm 2 Low Blood Pressure Control Lisinopril + Telmisartan (ACE-I + ARB) and low blood pressure control of 95-110/60-75 mm Hg Study A, Arm 1 Standard Blood Pressure Control Lisinopril + Telmisartan (ACE-I + ARB) and standard blood pressure control of 120-130/70-80 mm Hg Study A, Arm 3 Placebo Lisinopril + Placebo (ACE-I + Placebo) and standard blood pressure control of 120-130/70-80 mm Hg Study A, Arm 3 Standard Blood Pressure Control Lisinopril + Placebo (ACE-I + Placebo) and standard blood pressure control of 120-130/70-80 mm Hg Study A, Arm 4 Placebo Lisinopril + Placebo (ACE-I + Placebo) and low blood pressure control of 95-110/60-75 mm Hg Study A, Arm 4 Low Blood Pressure Control Lisinopril + Placebo (ACE-I + Placebo) and low blood pressure control of 95-110/60-75 mm Hg Study A, Arm 1 Telmisartan Lisinopril + Telmisartan (ACE-I + ARB) and standard blood pressure control of 120-130/70-80 mm Hg Study A, Arm 2 Lisinopril Lisinopril + Telmisartan (ACE-I + ARB) and low blood pressure control of 95-110/60-75 mm Hg Study A, Arm 2 Telmisartan Lisinopril + Telmisartan (ACE-I + ARB) and low blood pressure control of 95-110/60-75 mm Hg Study A, Arm 3 Lisinopril Lisinopril + Placebo (ACE-I + Placebo) and standard blood pressure control of 120-130/70-80 mm Hg Study A, Arm 4 Lisinopril Lisinopril + Placebo (ACE-I + Placebo) and low blood pressure control of 95-110/60-75 mm Hg
- Primary Outcome Measures
Name Time Method Study A: Percent Annual Change in Total Kidney Volume 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.
- Secondary Outcome Measures
Name Time Method 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) Short Form-36 Quality of LIfe Mental Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome)
Aldosterone Up to 96 months (assessed annually) Urinary aldosterone excretion, centrally processed, 24 hour urine collection
Quality of Life Physical Component Summary baseline, 12, 24, 36, 48, 60, 72, 84, and 96 months (assessed annually) Short Form-36 Quality of Life Physical Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome)
Kidney Function (eGFR) Up to 96 months (6 month assessments) The estimated GFR was calculated by means of the Chronic Kidney Disease Epidemiology Collaboration equation with the use of central serum creatinine measurements.
Left Ventricular Mass Index 0, 24 months, 48 months, 60 months Left ventricular mass index (g/m\^2) measured by MRI, centrally reviewed and measured
Albuminuria Up to 96 months (assessed annually) Urine albumin excretion, centrally processed from 24 hour urine collection
Renal Blood Flow 0, 24 months, 48 months, 60 months renal blood flow (mL/min/1.73 m\^2) from MRI, centrally reviewed and measured. This outcome was more difficult to measure resulting in more missing data than other MRI outcomes such as total kidney volume (TKV) and left ventricular mass index (LVMI).
Trial Locations
- Locations (7)
University of Colorado Health Sciences Center
🇺🇸Aurora, Colorado, United States
Tufts University-New England Medical Center
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States