A central factor in the pathogenesis of heart failure (HF) with reduced ejection 
fraction is the initial decrease in systolic function. Prior attempts at 
increasing cardiac contractility with oral drugs have uniformly resulted in 
signals of increased mortality at pharmacologically effective doses. Omecamtiv 
mecarbil is a novel, selective cardiac myosin activator that has been shown to 
improve cardiac function and to decrease ventricular volumes, heart rate, and 
N-terminal pro-B-type natriuretic peptide in patients with chronic HF. The 
GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through 
Improving Contractility in Heart Failure) trial tests the hypotheses that 
omecamtiv mecarbil can safely improve symptoms, prevent clinical HF events, and 
delay CV death in patients with chronic HF. The GALACTIC-HF trial is an 
international, multicenter, randomized, double-blind, placebo-controlled, 
event-driven cardiovascular outcomes trial. More than 8,000 patients with 
chronic symptomatic (New York Heart Association functional class II to IV) HF, 
left ventricular ejection fraction ≤35%, elevated natriuretic peptides, and 
either current hospitalization for HF or history of hospitalization or emergency 
department visit for HF within a year of screening will be randomized to either 
oral placebo or omecamtiv mecarbil employing a pharmacokinetic-guided dose 
titration strategy using doses of 25, 37.5, or 50 mg twice daily. The primary 
efficacy outcome is the time to cardiovascular death or first HF event. The 
study has 90% power to assess a final hazard ratio of approximately 0.80 in 
cardiovascular death, the first secondary outcome. The GALACTIC-HF trial is the 
first trial examining whether selectively increasing cardiac contractility in 
patients with HF with reduced ejection fraction will result in improved clinical 
outcomes. (Registrational Study With Omecamtiv Mecarbil/AMG 423 to Treat Chronic 
Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329).