Intravenous Iron in paTients With Heart failURe and Reduced Ejection fracTion (HFREF) pLus Iron dEficiency (Iron Turtle)
Primary Purpose
Heart Failure, Systolic, Iron Deficiency
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Ferric Carboxymaltose
blood withdrawal
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure, Systolic focused on measuring iron deficiency, HFREF, FGF23, ferric carboxymaltose
Eligibility Criteria
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
Sites / Locations
- Department of Medicine, Division of Cardiology, Pulmonary Diseases and Vascular Medicine at the University Hospital, RWTH Aachen
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Patients with HFREF & CKD
Patients with HFREF
Arm Description
treated with intravenous single-shot 1000mg Ferric Carboxymaltose infusion; additional intervention: blood withdrawal
treated with intravenous single-shot 1000mg Ferric Carboxymaltose infusion; additional intervention: blood withdrawal
Outcomes
Primary Outcome Measures
changes in blood intact FGF23 after infusion of 1000 mg ferric carboxymaltose
intact FGF23 concentration in kRU/l
changes in blood c-term FGF23 after infusion of 1000 mg ferric carboxymaltose
c-terminal FGF23 concentration in kRU/l
Secondary Outcome Measures
changes of serum biomarkers of chronic kidney disease metabolism
PTH, Vitamin D, ALP, s-klotho, PINP, proBNP
changes of urinary marker of tubular damage
NGAL, KIM-1
phosphate level
< 1,25 mg/dL
changes of Inflammatory mediators
IL1, IL6, TNF-alpha, hsCRP
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03079518
Brief Title
Intravenous Iron in paTients With Heart failURe and Reduced Ejection fracTion (HFREF) pLus Iron dEficiency
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
March 10, 2017 (Actual)
Primary Completion Date
October 25, 2017 (Actual)
Study Completion Date
October 25, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RWTH Aachen University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Systolic, Iron Deficiency
Keywords
iron deficiency, HFREF, FGF23, ferric carboxymaltose
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Non-Randomized
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Patients with HFREF & CKD
Arm Type
Active Comparator
Arm Description
treated with intravenous single-shot 1000mg Ferric Carboxymaltose infusion; additional intervention: blood withdrawal
Arm Title
Patients with HFREF
Arm Type
Active Comparator
Arm Description
treated with intravenous single-shot 1000mg Ferric Carboxymaltose infusion; additional intervention: blood withdrawal
Intervention Type
Drug
Intervention Name(s)
Ferric Carboxymaltose
Other Intervention Name(s)
Ferinject
Intervention Description
single shot infusion
Intervention Type
Other
Intervention Name(s)
blood withdrawal
Intervention Description
for determination of serum and urinary biomarkers of chronic kidney disease metabolism and other parameters
Primary Outcome Measure Information:
Title
changes in blood intact FGF23 after infusion of 1000 mg ferric carboxymaltose
Description
intact FGF23 concentration in kRU/l
Time Frame
4 weeks
Title
changes in blood c-term FGF23 after infusion of 1000 mg ferric carboxymaltose
Description
c-terminal FGF23 concentration in kRU/l
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
changes of serum biomarkers of chronic kidney disease metabolism
Description
PTH, Vitamin D, ALP, s-klotho, PINP, proBNP
Time Frame
4 weeks
Title
changes of urinary marker of tubular damage
Description
NGAL, KIM-1
Time Frame
4 weeks
Title
phosphate level
Description
< 1,25 mg/dL
Time Frame
4 weeks
Title
changes of Inflammatory mediators
Description
IL1, IL6, TNF-alpha, hsCRP
Time Frame
4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Department of Medicine, Division of Cardiology, Pulmonary Diseases and Vascular Medicine at the University Hospital, RWTH Aachen
City
Aachen
State/Province
NRW
ZIP/Postal Code
52074
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
IPD will not be shared due to publication afterwards
Citations:
PubMed Identifier
29747838
Citation
Stohr R, Sandstede L, Heine GH, Marx N, Brandenburg V. High-Dose Ferric Carboxymaltose in Patients With HFrEF Induces Significant Hypophosphatemia. J Am Coll Cardiol. 2018 May 15;71(19):2270-2271. doi: 10.1016/j.jacc.2018.03.448. No abstract available.
Results Reference
derived
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Intravenous Iron in paTients With Heart failURe and Reduced Ejection fracTion (HFREF) pLus Iron dEficiency
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