Clinical trial NCT00283686
Conditions: Kidney, Polycystic
Keywords: polycystic kidney disease polycystic kidney disease adpkd halt pkd blood pressure bp hypertension renal renin-angiotensin-aldosterone-system RAAS
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Start date: 2006-01-01; Completion date: 2014-06-01
Enrollment: 558 participants; Allocation: RANDOMIZED; Intervention model: FACTORIAL

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.

Arms: arm 1: Lisinopril + Telmisartan (ACE-I + ARB) and standard blood pressure control of 120-130/70-80 mm Hg arm 2: Lisinopril + Telmisartan (ACE-I + ARB) and low blood pressure control of 95-110/60-75 mm Hg arm 3: Lisinopril + Placebo (ACE-I + Placebo) and standard blood pressure control of 120-130/70-80 mm Hg arm 4: Lisinopril + Placebo (ACE-I + Placebo) and low blood pressure control of 95-110/60-75 mm Hg
Interventions: intervention 1: Lisinopril intervention 2: Telmisartan intervention 3: Placebo intervention 4: Standard Blood Pressure Control intervention 5: Low Blood Pressure Control
Intervention descriptions: intervention 1: Lisinopril titrated to 5mg, 10mg, 20mg, 40mg intervention 2: Telmisartan/Placebo titrated to 40mg and 80mg, as tolerated by participants intervention 3: Telmisartan/Placebo titrated to 40mg and 80mg, as tolerated by participants intervention 4: Achieve standard blood pressure control of 120-130/70-80 mm Hg using step dosing specified in protocol of lisinopril, study drug, hydrochlorothiazide, metoprolol, or non-dihydropyridine and dihydropyridine calcium channel blockers (diltiazem), clonidine, minoxidil, hydralazine at the discretion of the investigator intervention 5: Achieve low blood pressure control of 95-110/60-75 mm Hg using step dosing specified in protocol of lisinopril, study drug, hydrochlorothiazide, metoprolol, or non-dihydropyridine and dihydropyridine calcium channel blockers (diltiazem), clonidine, minoxidil, hydralazine at the discretion of the investigator

Protocol documents: