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

Iron Deficiency Clinical Trial

— Iron Turtle  

Official title:

Intravenous Iron in paTients With Heart failURe and Reduced Ejection fracTion (HFREF) pLus Iron dEficiency: Effects Upon Phosphate and FGF23 Metabolism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03079518
• Other study ID #: 16-047
• Status: Completed
• Phase: Phase 2
• First received: March 3, 2017
• Last updated: December 5, 2017
• Start date: March 10, 2017
• Est. completion date: October 25, 2017

Study information

• Verified date: December 2017
• Source: RWTH Aachen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: October 25, 2017
• Est. primary completion date: October 25, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Heart Failure
• Heart Failure, Systolic
• Iron Deficiency

Intervention

Drug:
• Ferric Carboxymaltose
single shot infusion

Other:
• blood withdrawal
for determination of serum and urinary biomarkers of chronic kidney disease metabolism and other parameters

Locations

Country	Name	City	State
Germany	Department of Medicine, Division of Cardiology, Pulmonary Diseases and Vascular Medicine at the University Hospital, RWTH Aachen	Aachen	NRW

Sponsors (1)

Lead Sponsor	Collaborator
RWTH Aachen University

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	changes in blood intact FGF23 after infusion of 1000 mg ferric carboxymaltose	intact FGF23 concentration in kRU/l	4 weeks
Primary	changes in blood c-term FGF23 after infusion of 1000 mg ferric carboxymaltose	c-terminal FGF23 concentration in kRU/l	4 weeks
Secondary	changes of serum biomarkers of chronic kidney disease metabolism	PTH, Vitamin D, ALP, s-klotho, PINP, proBNP	4 weeks
Secondary	changes of urinary marker of tubular damage	NGAL, KIM-1	4 weeks
Secondary	phosphate level	< 1,25 mg/dL	4 weeks
Secondary	changes of Inflammatory mediators	IL1, IL6, TNF-alpha, hsCRP	4 weeks