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

December 5, 2017 updated by: RWTH Aachen University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

23

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • NRW
      • Aachen, NRW, Germany, 52074
        • Department of Medicine, Division of Cardiology, Pulmonary Diseases and Vascular Medicine at the University Hospital, RWTH Aachen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Patients with HFREF & CKD
treated with intravenous single-shot 1000mg Ferric Carboxymaltose infusion; additional intervention: blood withdrawal
Drug: Ferric Carboxymaltose
single shot infusion
Other Names:
  • Ferinject
Other: blood withdrawal
for determination of serum and urinary biomarkers of chronic kidney disease metabolism and other parameters
ACTIVE_COMPARATOR: Patients with HFREF
treated with intravenous single-shot 1000mg Ferric Carboxymaltose infusion; additional intervention: blood withdrawal
Drug: Ferric Carboxymaltose
single shot infusion
Other Names:
  • Ferinject
Other: blood withdrawal
for determination of serum and urinary biomarkers of chronic kidney disease metabolism and other parameters

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
changes in blood intact FGF23 after infusion of 1000 mg ferric carboxymaltose
Time Frame: 4 weeks
intact FGF23 concentration in kRU/l
4 weeks
changes in blood c-term FGF23 after infusion of 1000 mg ferric carboxymaltose
Time Frame: 4 weeks
c-terminal FGF23 concentration in kRU/l
4 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

RWTH Aachen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 10, 2017

Primary Completion (ACTUAL)

October 25, 2017

Study Completion (ACTUAL)

October 25, 2017

Study Registration Dates

First Submitted

March 3, 2017

First Submitted That Met QC Criteria

March 8, 2017

First Posted (ACTUAL)

March 14, 2017

Study Record Updates

Last Update Posted (ACTUAL)

December 6, 2017

Last Update Submitted That Met QC Criteria

December 5, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16-047

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD will not be shared due to publication afterwards

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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