Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: The IRONOUT HF Randomized Clinical Trial

Randomized clinical trial in adults with heart failure with reduced ejection fraction (LVEF  40%) and iron deficiency who were stable on guideline-directed medical therapy. Participants were enrolled at 23 sites in the United States between September 2014 and November 2015.

Oral iron polysaccharide, 150 mg by mouth twice daily for 16 weeks, compared with placebo. The active intervention arm included 111 participants randomized to oral iron polysaccharide.

High-dose oral iron did not improve exercise capacity or related clinical outcomes over 16 weeks. The primary endpoint, change in peak VO2, was +23 mL/min with oral iron versus -2 mL/min with placebo, for a between-group difference of 21 mL/min (95% CI, -34 to +76; P = .46). The 6-minute walk distance changed by 15 m versus 21 m, with a difference in change of -1 m (95% CI, -24 to 23; P = .95), and NT-proBNP showed no meaningful between-group difference (159 pg/mL; P = .48). KCCQ clinical summary score also did not significantly differ (difference 3.4; P = .08), and adverse events were similar between groups (35% vs 39%; serious adverse events 10% vs 9%).

The treatment period was short at 16 weeks, which may limit detection of longer-term effects. The active-arm sample was modest, and the trial found no significant benefit across the primary and key secondary endpoints. Some baseline values and demographic details were not reported per arm, which limits more granular subgroup interpretation.