Rationale and design of the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure Trial (ASCEND-HF).
BACKGROUND
Acute decompensated heart failure (ADHF) is a major public health burden with significant mortality and morbidity. Nesiritide is a recombinantly produced intravenous formulation of human B-type natriuretic peptide that promotes vasodilation and increases salt and water excretion, which results in reduced cardiac filling pressures. Prior studies have shown that dyspnea is improved in patients with ADHF 3 hours after nesiritide infusion with significant dose-related reductions in cardiac filling pressures and systemic vascular resistance without significant arrhythmias. However, the effect of nesiritide on dyspnea at 6 or 24 hours is unknown, and no clinical outcome trials have been done to provide a reliable estimate of the effect of nesiritide on morbidity and mortality.


METHODS
The Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure trial (ASCEND-HF) is a phase III study evaluating the efficacy and safety of nesiritide in patients with ADHF. Patients hospitalized for hear failure will be randomly assigned to receive either intravenous nesiritide or matching placebo for 24 hours to 7 days. The 2 coprimary end points are (1) assessment of acute dyspnea at 6 or 24 hours and (2) death or rehospitalization for hear failure within 30 days. A total of 7,000 patients will be enrolled worldwide between 2007 and 2010.


CONCLUSIONS
The data from the ASCEND-HF trial will establish whether nesiritide safely improves acute dyspnea as well as morbidity and mortality at 30 days.
Hernandez
Adrian F
AF
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA. adrian.hernandez@duke.edu
O'Connor
Christopher M
CM
Starling
Randall C
RC
Reist
Craig J
CJ
Armstrong
Paul W
PW
Dickstein
Kenneth
K
Lorenz
Todd J
TJ
Gibler
W Brian
WB
Hasselblad
Vic
V
Komajda
Michel
M
Massie
Barry
B
McMurray
John J V
JJ
Nieminen
Markku
M
Rouleau
Jean L
JL
Swedberg
Karl
K
Califf
Robert M
RM
D004417:Dyspnea / Q000188:drug therapy / Q000209:etiology; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology; D006760:Hospitalization; D006801:Humans; D009017:Morbidity; D045283:Natriuretic Agents / Q000627:therapeutic use*; D020097:Natriuretic Peptide, Brain / Q000627:therapeutic use*; D012107:Research Design; D016019:Survival Analysis; D016896:Treatment Outcome
D045283:Natriuretic Agents; D020097:Natriuretic Peptide, Brain