title: Results of a non-specific immunomodulation therapy in chronic heart failure (ACCLAIM trial): a placebo-controlled randomised trial.
abstract: 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.
authors.affiliation: Heart Transplant Program, Methodist DeBakey Heart Center, Methodist Hospital, Houston, TX 77030, USA. gtorre@tmhs.org
authors.forename: Guillermo
authors.initials: G
authors.lastname: Torre-Amione
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bourge
authors.forename: Wilson S
authors.initials: WS
authors.lastname: Colucci
authors.forename: Barry H
authors.initials: BH
authors.lastname: Greenberg
authors.forename: Per
authors.initials: P
authors.lastname: Hildebrandt
authors.forename: Andre
authors.initials: A
authors.lastname: Keren
authors.forename: Michael
authors.initials: M
authors.lastname: Motro
authors.forename: Lemuel A
authors.initials: LA
authors.lastname: Moyé
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Otterstad
authors.forename: Craig M
authors.initials: CM
authors.lastname: Pratt
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.forename: Jean Lucien
authors.initials: JL
authors.lastname: Rouleau
authors.forename: Francois
authors.initials: F
authors.lastname: Sestier
authors.forename: Bernhard R
authors.initials: BR
authors.lastname: Winkelmann
authors.forename: James B
authors.initials: JB
authors.lastname: Young
mesh_terms: 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
chemical_list: D007155:Immunologic Factors