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 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

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)692-699
Number of pages8
JournalAmerican Journal of Kidney Diseases
Volume57
Issue number5
DOIs
StatePublished - May 2011

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Safety Management
Autosomal Dominant Polycystic Kidney
Kidney
Cysts
Placebos
Albuminuria
Renal Insufficiency
Creatinine
tolvaptan
TEMPO
Growth
Safety
Pain
Vasopressin Receptors
Polycystic Kidney Diseases
Vital Signs
Vasopressins
Sample Size
Population
Animal Models

Keywords

  • autosomal dominant polycystic kidney disease (ADPKD)
  • Clinical trial
  • polycystic kidney disease
  • vasopressin

ASJC Scopus subject areas

  • Nephrology

Cite this

Rationale and design of the TEMPO (tolvaptan efficacy and safety in management of autosomal dominant polycystic kidney disease and its outcomes) 3-4 study. / Torres, Vicente; Meijer, Esther; Bae, Kyongtae T.; Chapman, Arlene B.; Devuyst, Olivier; Gansevoort, Ron T.; Grantham, Jared J.; Higashihara, Eiji; Perrone, Ronald D.; Krasa, Holly B.; Ouyang, John J.; Czerwiec, Frank S.

In: American Journal of Kidney Diseases, Vol. 57, No. 5, 05.2011, p. 692-699.

Research output: Contribution to journalArticle

Torres, V, Meijer, E, Bae, KT, Chapman, AB, Devuyst, O, Gansevoort, RT, Grantham, JJ, Higashihara, E, Perrone, RD, Krasa, HB, Ouyang, JJ & Czerwiec, FS 2011, 'Rationale and design of the TEMPO (tolvaptan efficacy and safety in management of autosomal dominant polycystic kidney disease and its outcomes) 3-4 study', American Journal of Kidney Diseases, vol. 57, no. 5, pp. 692-699. https://doi.org/10.1053/j.ajkd.2010.11.029
Torres, Vicente ; Meijer, Esther ; Bae, Kyongtae T. ; Chapman, Arlene B. ; Devuyst, Olivier ; Gansevoort, Ron T. ; Grantham, Jared J. ; Higashihara, Eiji ; Perrone, Ronald D. ; Krasa, Holly B. ; Ouyang, John J. ; Czerwiec, Frank S. / Rationale and design of the TEMPO (tolvaptan efficacy and safety in management of autosomal dominant polycystic kidney disease and its outcomes) 3-4 study. In: American Journal of Kidney Diseases. 2011 ; Vol. 57, No. 5. pp. 692-699.
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AU - Meijer, Esther

AU - Bae, Kyongtae T.

AU - Chapman, Arlene B.

AU - Devuyst, Olivier

AU - Gansevoort, Ron T.

AU - Grantham, Jared J.

AU - Higashihara, Eiji

AU - Perrone, Ronald D.

AU - Krasa, Holly B.

AU - Ouyang, John J.

AU - Czerwiec, Frank S.

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