Results of a non-specific immunomodulation therapy in chronic heart failure (ACCLAIM trial): a placebo-controlled randomised trial.
BACKGROUND
Evidence suggests that inflammatory mediators contribute to development and progression of chronic heart failure. We therefore tested the hypothesis that immunomodulation might counteract this pathophysiological mechanism in patients.


METHODS
We did a double-blind, placebo-controlled study of a device-based non-specific immunomodulation therapy (IMT) in patients with New York Heart Association (NYHA) functional class II-IV chronic heart failure, left ventricular (LV) systolic dysfunction, and hospitalisation for heart failure or intravenous drug therapy in an outpatient setting within the past 12 months. Patients were randomly assigned to receive IMT (n=1213) or placebo (n=1213) by intragluteal injection on days 1, 2, 14, and every 28 days thereafter. Primary endpoint was the composite of time to death from any cause or first hospitalisation for cardiovascular reasons. The study continued until 828 primary endpoint events had accrued and all study patients had been treated for at least 22 weeks. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00111969.


RESULTS
During a mean follow-up of 10.2 months, there were 399 primary events in the IMT group and 429 in the placebo group (hazard ratio 0.92; 95% CI 0.80-1.05; p=0.22). In two prespecified subgroups of patients--those with no history of previous myocardial infarction (n=919) and those with NYHA II heart failure (n=689)--IMT was associated with a 26% (0.74; 0.57-0.95; p=0.02) and a 39% (0.61; 95% CI 0.46-0.80; p=0.0003) reduction in the risk of primary endpoint events, respectively.


CONCLUSIONS
Non-specific immunomodulation may have a role as a potential treatment for a large segment of the heart failure population, which includes patients without a history of myocardial infarction (irrespective of their functional NYHA class) and patients within NYHA class II.
Torre-Amione
Guillermo
G
Heart Transplant Program, Methodist DeBakey Heart Center, Methodist Hospital, Houston, TX 77030, USA. gtorre@tmhs.org
Anker
Stefan D
SD
Bourge
Robert C
RC
Colucci
Wilson S
WS
Greenberg
Barry H
BH
Hildebrandt
Per
P
Keren
Andre
A
Motro
Michael
M
Moyé
Lemuel A
LA
Otterstad
Jan Erik
JE
Pratt
Craig M
CM
Ponikowski
Piotr
P
Rouleau
Jean Lucien
JL
Sestier
Francois
F
Winkelmann
Bernhard R
BR
Young
James B
JB
D000368:Aged; D002908:Chronic Disease; D004311:Double-Blind Method; D023381:Endpoint Determination / Q000379:methods*; D005260:Female; D006333:Heart Failure / Q000145:classification / Q000503:physiopathology / Q000628:therapy*; D017052:Hospital Mortality; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index
D007155:Immunologic Factors