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Am Heart J. 2011 Jun;161(6):1012-23.e3. doi: 10.1016/j.ahj.2011.03.004.

Rationale, design, and results from RENO-DEFEND 1: a randomized, dose-finding study of the selective A1 adenosine antagonist SLV320 in patients hospitalized with acute heart failure.

Collaborators (172)

Gheorghiade M, Filippatos G, Maggioni A, Mehra M, Pang PS, Thygesen K, DeGroote P, Arnold M, Martinez F, Broncel M, Macarie C, Arutyunov G, Sefarovic P, Parkhomenko A, Alvarez C, Cartasegna L, Fernandez A, Fuselli JJ, Giacomi G, Guzman L, Hasbani E, Navarro JL, Patocchi C, Schygiel PO, Nguyen V, Rajda M, Nunez Peirano L, Araneda G, Cobos J, Escobar J, Larico M, Lopetegui M, Martinez D, Opazo M, Pedemonte O, Potthoff S, Stockins B, Venegas J, Nielsen T, Raymond I, Vejby-Christensen H, Nielsen H, Thygesen K, Wiggers H, Cohen Solal A, Cottin Y, De Groote P, Dos Santos P, Farah B, Funck F, Mettauer B, Behrens S, Fischer D, Flesch M, Kadel C, Kreuzer J, Mitrovic V, Schwinger R, Sueselbeck T, Winkler R, Zugck C, Benassi A, Carbonieri E, Fragasso G, Lo Pinto G, Montagna L, Paloscia L, Pirelli S, Sicuro M, Sinagra G, Gniot J, Ahremczyk P, Biedrzycka M, Broncel M, Bronisz M, Drzewiecki A, Galar B, Gasior Z, Jaworska K, Jonczy B, Kaminski L, Krauze-Wielicka M, Marcisz C, Mazurek W, Ozegowski S, Sciborski R, Tracz W, Bartos D, Bolohan F, Creteanu M, Dobre I, Macarie C, Minescu B, Pop C, Tomescu M, Arutyunov G, Ballyuzek M, Goloshchekin B, Karpov Y, Khasanov N, Khokhlov A, Kosmacheva E, Kostenko V, Libov I, Sayganov S, Shogenov Z, Sitnikova M, Tereschenko S, Vishnevsky A, Zadionchenko V, Zateyshchikov D, Zateyshchikova A, Borzanovic M, Grujic M, Ilic S, Krotin M, Neskovic A, Pavlovic M, Seferovic P, Goloborodko B, Karpenko O, Koval' O, Parkhomenko A, Potapenko P, Prokhorov O, Vakaliuk I, Yagensky Y, Al-Joundi B, Larned J, Ahmad A, Bareket Y, Barnum O, Berlin H, Chapman D, Char D, Chesoni S, Clarkson W, Clemson B, Courtney M, Goytia-Leos D, Gupta D, Heilman J, Hodsden J, Jafri S, Jain D, Johnson D, Kabour A, Karia D, Khouri S, Koganti D, Levy P, Mancini D, Marais H, Mather P, Morgan A, Moskovits N, Moskowitz R, Murphy A, Pearce D, Quinlan E, Raskin S, Saleh N, Scott C, Shapiro N, Skopicki H, Swerchowsky V, Taylor R, Tita C, Tunio J, Turk S, Ventura H, Walsh M.

Author information

Department of Emergency Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.



Baseline renal impairment as well as worsening renal function during hospitalization is associated with worse short- and long-term outcomes in patients hospitalized for acute heart failure (AHF). We hypothesized that selective A1 adenosine receptor blockade would induce natriuresis while preserving renal function in AHF patients with renal dysfunction.


A phase II, randomized, double-blind, placebo-controlled, parallel group, multicenter study to evaluate the efficacy and safety of 2.5, 7.5, 15, and 30 mg/d SLV320 (1 hour intravenous infusions of 1.25, 3.75, 7.5, and 15 mg SLV320, every 12 hours for 3 days [a total of 6 doses] in addition to standard therapy) in subjects hospitalized with AHF and renal impairment who meet all inclusion/exclusion criteria. The study planned to enroll 450 subjects, with 90 subjects allocated equally to each treatment arm.


The study was terminated early. The decision, which was unrelated to the study conduct or results, with a total of 46 subjects randomized. Of those randomized, 6:8:8:8 and 6 patients, respectively, completed the study in each of the dosing subgroups, with placebo as the fifth group. For the 1.25-mg study group, the mean age was 73 years; mean (SD) systolic blood pressure (SBP), 128.5 (16.2); heart rate, 80.8 (25.0); brain natriuretic peptide, 969.7 (571.28); creatinine (μmol/L), 149.7 (41.0); cystatin C, 1.468 (0.2777); estimated glomerular filtration rate, 33.8 (7.913); and blood urea nitrogen, 12.1 (2.9), with roughly similar values in each treatment arm. No seizures were reported during the study. Eight patients died during the study, none of whom were associated with the study drug per an independent, blinded, data safety monitoring board.


Because of the limited number of subjects and variability observed in the results, no definite conclusions can be made regarding the efficacy and safety of SLV320.


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