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

Phase 2

Completed

• Conditions: Heart Failure, Systolic; Iron Deficiency
• Interventions: Drug: Ferric Carboxymaltose; Other: blood withdrawal

• Registration Number: NCT03079518
• Lead Sponsor: RWTH Aachen University

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2017-03-03
• Study First Submitted QC: 2017-03-08
• Study Start: 2017-03-10
• Study First Posted: 2017-03-14
• Primary Completion: 2017-10-25
• Study Completion: 2017-10-25
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-05
• Last Update Posted: 2017-12-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients with HFREF & CKD	blood withdrawal	treated with intravenous single-shot 1000mg Ferric Carboxymaltose infusion; additional intervention: blood withdrawal
Patients with HFREF	blood withdrawal	treated with intravenous single-shot 1000mg Ferric Carboxymaltose infusion; additional intervention: blood withdrawal
Patients with HFREF & CKD	Ferric Carboxymaltose	treated with intravenous single-shot 1000mg Ferric Carboxymaltose infusion; additional intervention: blood withdrawal
Patients with HFREF	Ferric Carboxymaltose	treated with intravenous single-shot 1000mg Ferric Carboxymaltose infusion; additional intervention: blood withdrawal

Primary Outcome Measures

Name	Time	Method
changes in blood intact FGF23 after infusion of 1000 mg ferric carboxymaltose	4 weeks	intact FGF23 concentration in kRU/l
changes in blood c-term FGF23 after infusion of 1000 mg ferric carboxymaltose	4 weeks	c-terminal FGF23 concentration in kRU/l

Secondary Outcome Measures

Name	Time	Method
changes of serum biomarkers of chronic kidney disease metabolism	4 weeks	PTH, Vitamin D, ALP, s-klotho, PINP, proBNP
changes of urinary marker of tubular damage	4 weeks	NGAL, KIM-1
phosphate level	4 weeks	\< 1,25 mg/dL
changes of Inflammatory mediators	4 weeks	IL1, IL6, TNF-alpha, hsCRP

Trial Locations

Locations (1)

Department of Medicine, Division of Cardiology, Pulmonary Diseases and Vascular Medicine at the University Hospital, RWTH Aachen; 🇩🇪 Aachen, NRW, Germany