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

Peter Pang, Mandeep Mehra, Aldo P. Maggioni, Gerasimos Filippatos, Jayne Middlebrooks, Prasad Turlapaty, Dmitri Kazei, Mihai Gheorghiade

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
JournalAmerican Heart Journal
Volume161
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

Fingerprint

Adenosine
Heart Failure
Kidney
Clinical Trials Data Monitoring Committees
Placebos
Blood Pressure
Adenosine A1 Receptors
Safety
Cystatin C
Natriuresis
Brain Natriuretic Peptide
Blood Urea Nitrogen
Glomerular Filtration Rate
Acute Kidney Injury
Intravenous Infusions
Multicenter Studies
Creatinine
Seizures
Hospitalization
Therapeutics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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. / Pang, Peter; Mehra, Mandeep; Maggioni, Aldo P.; Filippatos, Gerasimos; Middlebrooks, Jayne; Turlapaty, Prasad; Kazei, Dmitri; Gheorghiade, Mihai.

In: American Heart Journal, Vol. 161, No. 6, 06.2011.

Research output: Contribution to journalArticle

Pang, Peter ; Mehra, Mandeep ; Maggioni, Aldo P. ; Filippatos, Gerasimos ; Middlebrooks, Jayne ; Turlapaty, Prasad ; Kazei, Dmitri ; Gheorghiade, Mihai. / 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. In: American Heart Journal. 2011 ; Vol. 161, No. 6.
@article{c9ce2509b3974f96a6facd9552be0047,
title = "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",
abstract = "Background: 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. Methods: 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. Results: 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. Conclusion: 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.",
author = "Peter Pang and Mandeep Mehra and Maggioni, {Aldo P.} and Gerasimos Filippatos and Jayne Middlebrooks and Prasad Turlapaty and Dmitri Kazei and Mihai Gheorghiade",
year = "2011",
month = "6",
doi = "10.1016/j.ahj.2011.03.004",
language = "English (US)",
volume = "161",
journal = "American Heart Journal",
issn = "0002-8703",
publisher = "Mosby Inc.",
number = "6",

}

TY - JOUR

T1 - Rationale, design, and results from RENO-DEFEND 1

T2 - A randomized, dose-finding study of the selective A1 adenosine antagonist SLV320 in patients hospitalized with acute heart failure

AU - Pang, Peter

AU - Mehra, Mandeep

AU - Maggioni, Aldo P.

AU - Filippatos, Gerasimos

AU - Middlebrooks, Jayne

AU - Turlapaty, Prasad

AU - Kazei, Dmitri

AU - Gheorghiade, Mihai

PY - 2011/6

Y1 - 2011/6

N2 - Background: 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. Methods: 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. Results: 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. Conclusion: 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.

AB - Background: 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. Methods: 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. Results: 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. Conclusion: 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.

UR - http://www.scopus.com/inward/record.url?scp=79958162478&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958162478&partnerID=8YFLogxK

U2 - 10.1016/j.ahj.2011.03.004

DO - 10.1016/j.ahj.2011.03.004

M3 - Article

VL - 161

JO - American Heart Journal

JF - American Heart Journal

SN - 0002-8703

IS - 6

ER -