Table 2: Ongoing Large Outcome Trials of Intravenous Iron in Heart Failure.

Study	FAIR-HF2	Affirm-AHF	HEART-FID	IRONMAN
ClinicalTrials.gov Registration Number	NCT03036462	NCT02937454	NCT03037931	NCT02642562
Actual Start Date	7 February 2017	3 April 2017	15 March 2017	August 2016
Estimated Completion Date	October 2020	June 2019	January 2021	February 2021
HF Duration	Chronic	Acute	Chronic	Chronic
Primary Outcome(s)	Combined HF hospitalisations and CV death	Combined HF hospitalisations and CV death	• Death at 1 year • HF hospitalisation at 1 year • Change in 6-minute walk time at 6 months	Combined HF hospitalisations and CV death
Duration of Follow-up	At least 1 year	1 year	1 year	Minimum 2.5 years from last patient recruited
Intervention	Ferric carboxymaltose	Ferric carboxymaltose	Ferric carboxymaltose	Iron (III) isomaltoside 1,000
Amount of Iron	1,000 mg IV bolus followed by optional 500–1,000 mg within first 4 weeks (up to a total of	2,000 mg), followed by 500 mg every 4 months except when haemoglobin is >16.0 g/dl or ferritin is >800 μg/l	First dose is undiluted bolus injection. Study treatment dose (ml) to be determined by the patient’s body weight and haemoglobin value at respective visits	15 mg/kg (maximum 750 mg). Two doses seven days apart (maximum combined dose of 1,500 mg). Repeated every 6 months as indicated by iron indices	20 mg/kg
Estimated Enrolment	1,200	1,100	3,014	1,300
Important Inclusion Criteria	• Patients with chronic HF present for at least 12 months • Confirmed presence of iron deficiency • Serum haemoglobin of 9.5–14.0 g/dl	• Current hospitalisation for an episode of acute HF • Iron deficiency • LVEF <50 % within 12 months prior to randomisation	• Stable HF (NYHA II-IV) on maximally-tolerated background therapy • LVEF ≤35 % • Haemoglobin >9.0 g/dl and <13.5 g/dl (females) or <15.0 g/ dl (males) • Serum ferritin <100 ng/ml or 100–300 ng/ml with TSAT <20 %. • Either documented hospitalisation for HF within 12 months of enrolment or elevated natriuretic peptides	• LVEF <45 % • NYHA class II-IV • Iron deficient, defined as TSAT <20 % and/or ferritin <100 μg/l • Current or recent HF hospitalisation within 6 months for HF or elevated natriuretic peptides

Affirm-AHF = Study to Compare Ferric Carboxymaltose with Placebo in Patients with Acute Heart Failure and Iron Deficiency; CV = cardiovascular; FAIR-HF2 = Intravenous Iron in Patients with Systolic Heart Failure and Iron Deficiency to Improve Morbidity and Mortality; HEART-FID = Randomized Placebo-controlled Trial of FCM as Treatment for Heart Failure with Iron Deficiency; HF = heart failure; IRONMAN = Intravenous Iron Treatment in Patients with Heart Failure and Iron Deficiency; LVEF = left ventricular ejection fraction; NYHF = New York Heart Failure;

TSAT = transferring saturation.