Rationale and design of the multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy of vasopressin antagonism in heart failure: Outcome study with Tolvaptan (EVEREST)

Mihai Gheorghiade, Cesare Orlandi, John C. Burnett, David Demets, Liliana Grinfeld, Aldo Maggioni, Karl Swedberg, James E. Udelson, Faiez Zannad, Christopher Zimmer, Marvin A. Konstam, M. C. Bahit, M. Haass, P. E. Carson, P. J. Hauptman, M. Metra, A. Miller, C. O’connor, R. M. Oren, R. PattenI. Pina, Sherryn Roth, J. Sackner-Bernstein, H. Dargie, D. L. Demets, K. Dickstein, B. Greenberg, S. Goldstein, J. Lerman, B. Massie, B. Pitt, J. Ouyang, J. Udelson, H. A. Dieterich, Z. Capkova, F. Gadaleta, M. Mule, M. B. Pricipato, Martin Bilsker, Timothy Bishop, Dennis Bresnahan, David Caskey, Andrew Chai, Eugene Chung, Robert Mel Clark, William Dec, Gary Fishbein, Scott Friedman, Jalal Ghali, Alan Gradman, David Richards, Connor Haugh, David Hinchman, Hassan Ibrahim, Michael Imburgia, Eli Roth, Rafael Sequeira, Robert Siegel, Phil Stockwell, Kris Vijay, Tania Nanevicz, Robert Weiss, Richard Wright, Jay Alexander, Larry Altschul, Mohammad Ashraf, James Bergin, Chris Brown, Robert Capodilupo, Robert Carhart, James Carley, Barry Clemson, Terence Connelly, John Corbelli, Robert Doroghazi, Eric Eichhorn, Mahfouz El-Shahawy, John Foley, Mark Goldberg, David Goldscher, Steven Goldsmith, Terrence Hack, Ethan Haskel, David Hassel, Paul Hauptman, Pamela Rama, Philip Houck, Donald Jansen, Scott Jerome, Yamil Aude, David Joyce, Richard Kachel, Shaival Kapadia, Robert Kipperman, Richard Krasuski, Marvin Kronenberg, Farhad Aduli, Michael Liston, James Hodsen, James McCriskin, Frank McGrew, Robert Shor, Karan Munuswamy, Puneet Narayan, Imran Niazi, E. Dean Nukta, John O’brien, Joseph O’bryan, Maria Teresa Olivari, Mary Ann Peberdy, Mark Jeffrey Pirwitz, Rakesh Prashad, David Rubin, Jonathan Safren, Mitchell Saltzberg, Gregg Schuyler, Jonathan Roberts, Bramah Singh, Rodolfo Sotolongo, David Stagaman, Dwight Stapleton, William Van Decker, Charles Wilkins, Mohamad El-Zaru, Brian Kahn, Joseph Lash, John Banas, Supratim Banerjee, Marlo Leonen, Raymond Benza, Harry Colfer, Edouard Daher, Peter Fattal, Jack Foster, Peter Goodfield, Dinesh Gupta, William Hathaway, Herbert Haught, Tetsuo Ishimori, Bruce Iteld, Michael Kesselbrenner, Marc Klapholz, Peter McCullough, John Cieszkowski, Edward McMillan, Andrew Boyle, Mark Nathan, Terrence O’brien, Gary Felker, William Oellerich, Naveen Pereira, James Sandberg, Ernst Schwarz, Ralph Vicari, Frederick Whittier, Rene Alvarez, Alan Bank, Fred Cobb, David Cullinane, Himadri Dasgupta, J. T. Heywood, Steve Krueger, Brian Lowes, Jack Rose, Joel Sklar, J. Thomas Suh, Nampalli Vijay, Mary Walsh, Doug Chapman, Justine Lachmann, John Gordon, David Kraus, Brent Devries, Kirk Adams, Rachel Bijou, Uri Elkayam, Kenneth Fath, Hillel Ribner, John Schmedtje, Bruce Jackson, Joseph Wight, Michael Miyamoto, Hal Skopicki, Robert Frantz, Marrick Kukin, John McBride, Lana Tsao, Richard Ryder, Michael Koren, Kenneth Taylor, Kathy Hebert, Mara Slawsky, Narendra Singh, Christopher Brian, Syed Jafri, David Smith, Van Stephen Monroe, Mitchell Greenspan, Marc Silver, Lynne Wagoner, Ricky Schneider, Robert Moskowitz, Muhammad Yasin, Douglas Waldo, Tali Arik, Anique Ducharme, Bruce Sussex, Asaad Bakbak, David Borts, Y. K. Chan, L. John Charles, Nadia Giannetti, J. E. Goode, W. Peter Klinke, Jan Kornder, Peter Giannoccaro, Simon Kouz, Jacques Lenis, Serge Lepage, Gordon Moe, Andrew Morris, Yves Pesant, Diego Delgado, Thao Huynh, Patrick Ma, Frank Halperin, Thomas Rebane, A. S. Pandey, Jorge Tronge, Norberto Vulcano, Julio Jorge Bluguermann, Miguel Angel Riccitelli, Sergio Martin Chekherdemian, Roberto Colque, Marcos Amuchastegui, Eduardo Roque Perna, Aristóbulo Enrique Ballestrini, Alejandro Posadas, Ana Maria Salvatti, Luis Girotti, Susana Llois, Monica Sultan, Oscar Grosso, Carlos Estrada, Simón Mario Salzberg, Daniel Nul, Luis Guzmán, Marcelo Halac, Sergio Perrone, Alvaro Sosa Liprandi, Antonio Carlos Pereira Barreto, Celso Blacher, Euler Roberto Fernandes, Gilson Soares Feitosa, Gilmar Valdir Greque, Gilmar Reis, José Marcio Ribeiro, Lilia Nigro Maia, Pedro Pimentel Filho, Salvador Rassi, Paulo Rossi, Alvaro Rabelo Junior, Nadine Clausell, José Francisco Kerr Saraiva, Lilian Soares da Costa, Maria Sanali Moura de Oliveira Paiva, Denilson Albuquerque, Humberto Villacorta Junior, João Carlos Rocha, Jean Paul Salembier, Filip Charlier, Laurence Gabriel, Gilles De Keulenaer, Josef Jandik, Eva Mandysova, Frantisek Padour, Petr Vojtisek, Jiri Vitovec, Lubor Golan, Lenka Hoskova, Dag Tichy, Josef Drazka, David Alan, Ivo Oral, Jiri Janousek, Bohuslav Cernosek, Francois Delahaye, Marc Ferriere, Michel Galinier, Jean Noël Trochu, Thierry Laperche, Zukai Chati, Pierre Gibelin, Nadir Benazza, Michel Martelet, Hermann Ochs, Harald Darius, Thomas Dengler, Raimund Erbel, Hans Figulla, Rainer Hambrecht, Gerd Hasenfuss, Michael Buerke, Robert Schwinger, Stephan Felix, Wolfgang von Scheidt, Stephan Holmer, Juergen Kolditz, Thomas Wichter, Dieter Horstkotte, Hans Neuser, Gerhard Hauf, Holger Vogelshberg, Luigi Tavazzi, Claudio Marabotti, Maurizio Porcu, Silvio Ricci, Tiziano Moccetti, Giovanni Ruggeri, Cristina Opasich, Franco Cosmi, Franco Masini, Pierfranco Terrosu, Vincenzo Cirrincione, Franco Cobelli, Ernesto Murena, Piergiuseppe Agostoni, Pantaleo Giannuzzi, Don Hertzberger, Anho Liem, Walther Jap, Eugene Buys, Frank Den Hartog, Pieter van der Burgh, Gerard Louis Bartels, Jan Wesdorp, Dirk Lok, Angela Maas, Rolf Veldkamp, Paul A.R. de Milliano, Torbjorn Omland, Christian Ostvold, Vernon Bonarjee, Anne Semb, Jacek Grzybowski, Wladyslav Sinkiewicz, Jerzy Kopaczewski, Malgorzata Krzciuk, Janusz Maciejewicz, Andrzej Malinski, Michal Ogorek, Wladyslaw Pluta, Ryszard Sciborski, Tomasz Waszyrowski, Grzegorz Opolski, Krystyna Jaworska, Piotr Ruszkowski, Fryderyk Prochaczek, Radu Capalneanu, Mircea Cinteza, Mihail Dan Datcu, Carmen Georgeta Fierbinteanu Braticevici, Dorel Nastase-Melicovici, Dan Ionescu, Cezar Eugen Macarie, Ioan Tiberiu Nanea, Mariana Radoi, Gabriel Petrisor Tatu-Chitoiu, Stefan Dragulescu, Carmen Ginghina, Félix Pèrez-Villa, Josè Maria Arizón, Jordi Mercé, Juan Delgado, Angel Grande, Pedro Montes, Francisco Ridocci, Manuel Vida, Thomas Kahan, Ulf Dahlström, Cecilia Linde, Gerhard Wikström, Bengt Johansson, Inger Hagerman, Ronnie Willenheimer, Bengt Widgren, John Cleland, Mirza Baig, Steven Lindsay, Jatinder Dhawan, Iain Square, Robert Bain, Anatoly Baranov, Nikolai Gratsiansky, Maria Sitnikova, Konstantin Zrazhevsky, Victor Kostenko, Vladimir Simanenkov, Olga Berkovich, Vagan Mkrtchuan, Mikhail Boyarkin, Raisa Stryuk, Vecheslav Mareev, Vladislav Novozhenov, Sergey Shustov, Lev Sorokin, Vladimir Zadionchenko, Nikita B. Perepech, Boris M. Tankhileitch, Gennady I. Storozhakov, Igor Bokarev, Natalia Sanina, A. Martynov, Sergey Chernov, Sidorienko, Marina Ballyusek

Research output: Contribution to journalArticle

153 Scopus citations

Abstract

Background: Hospitalizations for worsening heart failure due to fluid overload (congestion) are common. Agents that treat congestion without causing electrolyte abnormalities or worsening renal function are needed. Tolvaptan is an oral vasopressin (V2) antagonist that decreases body weight and increases urine volume without inducing renal dysfunction or hypokalemia. The Efficacy of Vasopressin antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial is evaluating mortality, morbidity, and patient-assessed global clinical status in patients treated with tolvaptan compared with standard care. Methods and Results: Patients are eligible for inclusion if they have a reduced left ventricular ejection fraction and are hospitalized for worsening heart failure with evidence of systemic congestion. Patients are randomized 1:1 to tolvaptan 30 mg/day or matching placebo for a minimum of 60 days. Time to all-cause mortality and time to cardiovascular mortality or heart failure hospitalization are the coprimary end points. Patient-assessed global clinical status and quality of life are also evaluated. EVEREST will be continued until 1065 deaths occur. As of April 18, 2005, 2260 patients have been enrolled. Conclusion: Tolvaptan has been shown to reduce body weight in patients with worsening heart failure without inducing renal dysfunction or causing hypokalemia. The results of EVEREST will determine whether these effects translate into improved clinical outcomes.

Original languageEnglish (US)
Pages (from-to)260-269
Number of pages10
JournalJournal of cardiac failure
Volume11
Issue number4
DOIs
StatePublished - May 1 2005

Keywords

  • Clinical trials
  • Heart failure
  • Morbidity
  • Mortality
  • Vasopressin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Gheorghiade, M., Orlandi, C., Burnett, J. C., Demets, D., Grinfeld, L., Maggioni, A., Swedberg, K., Udelson, J. E., Zannad, F., Zimmer, C., Konstam, M. A., Bahit, M. C., Haass, M., Carson, P. E., Hauptman, P. J., Metra, M., Miller, A., O’connor, C., Oren, R. M., ... Ballyusek, M. (2005). Rationale and design of the multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy of vasopressin antagonism in heart failure: Outcome study with Tolvaptan (EVEREST). Journal of cardiac failure, 11(4), 260-269. https://doi.org/10.1016/j.cardfail.2005.03.009