COMPARATIVE STUDY
JOURNAL ARTICLE
MULTICENTER STUDY
RANDOMIZED CONTROLLED TRIAL

Rationale and design of the TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and its Outcomes) 3-4 Study

Vicente E Torres, Esther Meijer, Kyongtae T Bae, Arlene B Chapman, Olivier Devuyst, Ron T Gansevoort, Jared J Grantham, Eiji Higashihara, Ronald D Perrone, Holly B Krasa, John J Ouyang, Frank S Czerwiec
American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation 2011, 57 (5): 692-9
21333426

BACKGROUND: Current management of autosomal dominant polycystic kidney disease (ADPKD) is focused on treating disease complications, not on slowing cyst development or preventing progression to kidney failure. Tolvaptan, a selective vasopressin V2 (vasopressin 2) receptor antagonist, has been proved to inhibit kidney cyst growth and preserve kidney function in multiple animal models of polycystic kidney disease. The TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) 3-4 Study will examine the long-term effectiveness and safety of tolvaptan in patients with ADPKD. We report baseline characteristics and revised power calculations for the trial.

STUDY DESIGN: A prospective, 3-year, multicenter, double-blind, placebo-controlled trial of tolvaptan, a selective V2 receptor antagonist. Primary outcome is total kidney volume percentage of change from baseline for tolvaptan relative to placebo. Secondary outcome parameters include time to ADPKD-associated complications (kidney function decrease, blood pressure control, renal pain, and albuminuria) and safety end points.

SETTING & PARTICIPANTS: This trial includes patients with ADPKD with relatively preserved kidney function (baseline estimated creatinine clearance ≥60 mL/min), aged 50 years or younger, and with total kidney volume measured using magnetic resonance imaging ≥750 mL.

INTERVENTION: Administration of placebo or tolvaptan, dose titrated to tolerance.

OUTCOMES: Number of subjects enrolled and baseline characteristics.

MEASUREMENTS: Total kidney volume, kidney function, albuminuria, kidney pain, and vital signs.

RESULTS: 1,445 patients with ADPKD were enrolled between March 2007 and January 2009. Preliminary baseline median total kidney volume was 1.46 L, and estimated creatinine clearance was 105 ± 34 mL/min. A prespecified blinded sample-size recalculation at two-thirds enrollment confirmed the likely power of the study to detect 20% differences from placebo in the primary and key secondary end points at P < 0.05.

LIMITATIONS: This is a preselected ADPKD population chosen for its risk of progression to kidney failure and may not represent the general ADPKD population. If study results are positive with regard to the primary end point, positive effects on other secondary clinical outcomes will be required to assess overall benefit.

CONCLUSIONS: This randomized trial is the largest clinical study of a proposed ADPKD intervention to date. It targets patients with ADPKD with early disease who are projected to have rapid cyst growth and accelerated outcomes. Blockade of vasopressin V2 receptor is hypothesized to inhibit cyst growth, thereby delaying additional adverse clinical outcomes.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
21333426
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"