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

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ClinicalTrials.gov Identifier: NCT03079518
Recruitment Status : Completed
First Posted : March 14, 2017
Last Update Posted : December 6, 2017
Sponsor:
Information provided by (Responsible Party):
RWTH Aachen University

Tracking Information
First Submitted Date  ICMJE March 3, 2017
First Posted Date  ICMJE March 14, 2017
Last Update Posted Date December 6, 2017
Actual Study Start Date  ICMJE March 10, 2017
Actual Primary Completion Date October 25, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 16, 2017)
  • changes in blood intact FGF23 after infusion of 1000 mg ferric carboxymaltose [ Time Frame: 4 weeks ]
    intact FGF23 concentration in kRU/l
  • changes in blood c-term FGF23 after infusion of 1000 mg ferric carboxymaltose [ Time Frame: 4 weeks ]
    c-terminal FGF23 concentration in kRU/l
Original Primary Outcome Measures  ICMJE
 (submitted: March 8, 2017)
changes in blood FGF23 after infusion of 1000 mg ferric carboxymaltose [ Time Frame: 4 weeks ]
c-terminal FGF23 concentration in kRU/l
Change History Complete list of historical versions of study NCT03079518 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2017)
  • changes of serum biomarkers of chronic kidney disease metabolism [ Time Frame: 4 weeks ]
    PTH, Vitamin D, ALP, s-klotho, PINP, proBNP
  • changes of urinary marker of tubular damage [ Time Frame: 4 weeks ]
    NGAL, KIM-1
  • phosphate level [ Time Frame: 4 weeks ]
    < 1,25 mg/dL
  • changes of Inflammatory mediators [ Time Frame: 4 weeks ]
    IL1, IL6, TNF-alpha, hsCRP
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intravenous Iron in paTients With Heart failURe and Reduced Ejection fracTion (HFREF) pLus Iron dEficiency
Official Title  ICMJE Intravenous Iron in paTients With Heart failURe and Reduced Ejection fracTion (HFREF) pLus Iron dEficiency: Effects Upon Phosphate and FGF23 Metabolism
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Heart Failure, Systolic
  • Iron Deficiency
Intervention  ICMJE
  • Drug: Ferric Carboxymaltose
    single shot infusion
    Other Name: Ferinject
  • Other: blood withdrawal
    for determination of serum and urinary biomarkers of chronic kidney disease metabolism and other parameters
Study Arms  ICMJE
  • Active Comparator: Patients with HFREF & CKD
    treated with intravenous single-shot 1000mg Ferric Carboxymaltose infusion; additional intervention: blood withdrawal
    Interventions:
    • Drug: Ferric Carboxymaltose
    • Other: blood withdrawal
  • Active Comparator: Patients with HFREF
    treated with intravenous single-shot 1000mg Ferric Carboxymaltose infusion; additional intervention: blood withdrawal
    Interventions:
    • Drug: Ferric Carboxymaltose
    • Other: blood withdrawal
Publications * Stöhr 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 5, 2017)
23
Original Estimated Enrollment  ICMJE
 (submitted: March 8, 2017)
24
Actual Study Completion Date  ICMJE October 25, 2017
Actual Primary Completion Date October 25, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03079518
Other Study ID Numbers  ICMJE 16-047
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: IPD will not be shared due to publication afterwards
Responsible Party RWTH Aachen University
Study Sponsor  ICMJE RWTH Aachen University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account RWTH Aachen University
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP