Intravenous Iron in paTients With Heart failURe and Reduced Ejection fracTion (HFREF) pLus Iron dEficiency (Iron Turtle)

RWTH Aachen University

Status and phase: Completed; Phase 2

Conditions: Iron Deficiency; Heart Failure, Systolic

Treatments: Other: blood withdrawal; Drug: Ferric Carboxymaltose

Study type: Interventional

Funder types: Other

Identifiers

NCT03079518

16-047

Details and patient eligibility

About

Effects of ferric carboxymaltose single HD (1000 mg) infusion upon FGF23 in patients with isolated HFREF compared to patients with HFREF+CKD (all pts with iron deficiency). This study aims at identification of the optimal target population for a follow-up ("main") study.

Full description

Iron deficiency is highly prevalent in patients with HFREF and intravenous high-dose (HD) iron application has significantly improved clinically meaningful endpoints in such patients. The best evidence is existent for ferric carboxymaltose. Intravenous HD iron may influence phosphate metabolism via increases in levels of intact FGF23 and hence induce prolonged hypophosphatemia. Such increases in FGF23 may particularly occur depending on the type of iron carrier.

FGF23 is a significant risk factor for mortality and morbidity in patients with HFREF and other cardiac populations at risk and may directly cause left ventricular hypertrophy and dysfunction. Hence, the application of i.v. HD iron may have potentially beneficial effects on cardiac function but harmful effects via FGF23-induction and hypophosphatemia at the same time. However, FGF23 metabolism has not yet been evaluated in HFREF patients following i.v. HD iron.

FGF23 is elevated in patients with chronic kidney disease. Patients with HFREF + CKD = chronic cardio-renal syndrome are at particular risk regarding elevated morbidity and mortality. The effects of intravenous HD iron upon phosphate and FGF23 metabolism in patients with HFREF + CKD is unknown and effects in this setting may be different compared to effects in patients without pre-existing FGF23 stimulation.

Enrollment: 23 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Written informed consent.
• Age > 18 yrs
• Symptomatic HFREF (LV ejection fraction < 45%) with optimal medical therapy (OMT) for at least 2 months
• Iron deficiency as indicated by by ferritin <100 ng/mL or ferritin 100-299 ng/ml when transferrin saturation (TSAT) <20% and Hb value < 13mg/dl (women) and <14 mg/dl (men)
• Group A: Stable CKD for at least 2 months, defined by estimated glomerular filtration rate (eGFR) (CKD-EPI formula) as 15-60 ml/min/1,73 m3 (CKD III, IV, V-non D)
• Group B: patients with stable eGFR > 60 ml/min/1,73 m3

Exclusion criteria

• Known hypersensitivity to ferric carboxymaltose or any constituents of the formulation,
• Plasma Phosphate < 2.5 mg/dL at screening,
• Renal replacement therapy/transplantation,
• Pregnancy or lactation
• iron substitution therapy or erythropoetin (epo) therapy within 6 weeks before
• participation in another clinical trial with an experimental drug
• expectation of missing compliance
• alcohol or drug abuse
• The subject is mentally or legally incapacitated
• patients who are in a relationship of dependence or in a working relationship to the sponsor, the investigator or his representative

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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23 participants in 2 patient groups

Patients with HFREF & CKD

Active Comparator group

Description:

treated with intravenous single-shot 1000mg Ferric Carboxymaltose infusion; additional intervention: blood withdrawal

Treatment:

Drug: Ferric Carboxymaltose

Other: blood withdrawal

Patients with HFREF

Active Comparator group

Description:

treated with intravenous single-shot 1000mg Ferric Carboxymaltose infusion; additional intervention: blood withdrawal

Treatment:

Drug: Ferric Carboxymaltose

Other: blood withdrawal