Current management of ADPKD is focused on managing disease complications, not on slowing cyst development or preventing progression to kidney failure. Tolvaptan, a selective vasopressin V2 receptor antagonist, has proven to inhibit kidney cyst growth and preserve kidney function in multiple animal models of polycystic kidney disease. The TEMPO¾ trial will examine the long-term effectiveness and safety of tolvaptan in ADPKD patients.
A prospective, three-year, multicenter, double-blind, placebo controlled trial.
Setting & Participants
This trial includes ADPKD patients with a relatively preserved kidney function (baseline eCrCl ≥ 60 mL/min) ≤ 50 years of age and total kidney volume (TKV) measured with magnetic resonance imaging (MRI) ≥ 750 mL
Administration of placebo or tolvaptan, a selective V2 receptor antagonist, dose-titrated to tolerance.
Primary outcome is TKV percent change from baseline for tolvaptan relative to placebo. Secondary outcome parameters include time to ADPKD associated complications (renal function decline, blood pressure control, renal pain and albuminuria) and safety endpoints.
Measurements included TKV, kidney function, albuminuria, kidney pain, adverse events and vital signs.
Between March 2007 and January 2009, 1445 ADPKD patients were enrolled. Preliminary baseline median TKV was 1.46 L and eCrCl was 105 ± 34 mL/min. A pre-specified, blinded, sample size re-calculation at 2/3 enrollment confirmed the likely power of the study to detect 20% differences from placebo in the primary and key secondary endpoints at p<0.05.
This is a preselected ADPKD population chosen for its risk for progression to renal failure and may not represent the general ADPKD population. If the study results are positive with regard to the primary endpoint, confirmation among secondary clinical outcomes will be required.
Results from this randomized clinical trial will show whether treatment with a vasopressin V2 receptor antagonist effectively inhibits cyst growth and disease progression defined as a reduction in change in TKV in ADPKD patients.