Intravenous Iron in Patients With Systolic Heart Failure and Iron Deficiency to Improve Morbidity & Mortality (FAIR-HF2)

December 28, 2022 updated by: Universitätsklinikum Hamburg-Eppendorf

Intravenous Iron in Patients With Systolic Heart Failure and Iron Deficiency to Improve Morbidity & Mortality - FAIR-HF2

The purpose of this study is to determine whether intravenous iron supplementation using ferric carboxymaltosis (FCM) reduces hospitalisation and mortality in patients with iron deficiency and heart failure.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The clinical trial is designed as an international, prospective, multi-centre, double-blind, parallel group, randomised, controlled, interventional trial to investigate whether a long-term therapy with i.v. iron (ferric carboxymaltosis) compared to placebo can reduce the rate of recurrent heart failure hospitalisations and cardiovascular (CV) death in patients with heart failure with reduced ejection fraction (HFrEF).

I.v. iron administration in the form of ferric carboxymaltosis (FCM) will be carried out according to the Summary of Product Characteristics (SmPC). Bolus administration (1000 mg) will be followed by an optional administration of 500-1000 mg within the first 4 weeks (up to a total of 2000 mg which is in-label) according to approved dosing rules, followed by administration of 500 mg FCM at every 4 months, except when haemoglobin is > 16.0 g/dL or ferritin is > 800 µg/L.

In the verum group, all patients will receive a saline administration, when no iron is indicated at the time of the visit and according to the values listed above. Patients originally assigned to the placebo group will receive a saline administration at all visits.

In the control group i.v. NaCl at a volume according to the dosing rules for FCM at all visits will be administered in a double-blind manner.

Study Type

Interventional

Enrollment (Anticipated)

1200

Phase

  • Phase 4

Contacts and Locations

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

Study Contact

  • Name: Mahir Karakas, MD
  • Phone Number: 57975 0049 407410
  • Email: m.karakas@uke.de

Study Contact Backup

Study Locations

  • Germany
      • Bad Friedrichshall, Germany, 74177
        • Recruiting
        • SLK-Kliniken Heilbronn GmbH Klinikum am Plattenwald
        • Contact:
        • Contact:
          • Cornelia Neatu, Dr. med.
      • Bad Nauheim, Germany, 61231
        • Recruiting
        • Kerckhoff Klinik Bad Nauheim
        • Contact:
          • Christian W Hamm, MD
      • Berlin, Germany, 10789
        • Withdrawn
        • Studienzentrum Rankestrasse
      • Berlin, Germany, 12203
        • Recruiting
        • Universitätsmedizin Berlin Campus Benjamin Franklin
        • Contact:
          • David M Leistner, MD
      • Berlin, Germany, 13353
        • Recruiting
        • Charite Berlin (Campus Virchow-Klinikum)
        • Contact:
          • Frank Edelmann, MD
      • Bremen, Germany, 28277
        • Recruiting
        • Stiftung Bremer Herzen Bremer Institut für Herz- und Kreislauf- Forschung
        • Contact:
          • Harm Wienbergen, MD
      • Dresden, Germany, 01307
        • Active, not recruiting
        • Herzzentrum Dresden, Universitätsklinik
      • Greifswald, Germany, 17475
        • Recruiting
        • Uniklinik Greifswald, Klinik und Poliklinik für Innere Medizin B
        • Contact:
          • Daniel Beug, MD
      • Göttingen, Germany, 37075
        • Recruiting
        • Universitätsmedizin Göttingen
        • Contact:
          • Stephan von Haehling, MD
      • Halle, Germany, 06120
        • Active, not recruiting
        • Universitätsklinikum Halle (Saale)
      • Hamburg, Germany, 22041
      • Hamburg, Germany, 20251
        • Recruiting
        • Universitärsklinikum Hamburg-Eppendorf
        • Contact:
          • Mahir Karakas, MD
      • Heidelberg, Germany, 69120
        • Recruiting
        • Universitätsklinikum Heidelberg
        • Contact:
          • Lutz Frankenstein, MD
      • Homburg, Germany, 66421
        • Recruiting
        • Universitätsklinikum des Saarlandes
        • Contact:
          • Ingrid Kindermann, MD
      • Jena, Germany, 07747
      • Kiel, Germany, 24105
        • Recruiting
        • Universitätsklinikum Schleswig-Holstein Campus Kiel
        • Contact:
          • Mark Luedde, MD
      • Lübeck, Germany, 23538
        • Recruiting
        • Universitätsklinikum Schleswig-Holstein Campus Lübeck
        • Contact:
          • Tobias Graf, MD
        • Principal Investigator:
          • Tobias Graf, MD
      • Magdeburg, Germany, 39120
        • Recruiting
        • Universitätsklinikum Magdeburg
        • Contact:
          • Alexander Schmeißer, MD
      • Mainz, Germany, 55131
        • Recruiting
        • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
        • Contact:
          • Tommaso Gori, MD
      • Mannheim, Germany, 68167
        • Recruiting
        • Universitätsmedizin Mannheim
        • Contact:
          • Christina Dösch, MD
      • Mönchengladbach, Germany, 41063
        • Terminated
        • Kliniken Maria Hilf GmbH, Innere Medizin II, Klinik für Kardiologie
      • Mühldorf, Germany, 84453
        • Terminated
        • Praxis Dr. Schön Mühldorf
      • München, Germany, 81377
        • Recruiting
        • LMU München Medizinische Klinik und Poliklinik 1
        • Contact:
          • Stefan Kääb, Prof. Dr.
        • Principal Investigator:
          • Stefan Kääb, Prof. Dr.
      • München, Germany, 81675
        • Active, not recruiting
        • Klinikum rechts der Isar I. Medizinische Klinik und Poliklinik
      • Nürnberg, Germany, 90402
        • Recruiting
        • Gemeinschaftspraxis Hagenmiller/ Jeserich
        • Contact:
          • Michael Jeserich, MD
      • Nürnberg, Germany, 90471
        • Terminated
        • Universitätsklinik Medizinische Klinik 8 - Kardiologie Paracelsus Medizinische Privatuniversität Klinikum Nürnberg, Campus Süd
      • Remscheid, Germany, 42853
        • Recruiting
        • KardioPrax Remscheid
        • Contact:
          • Detlev Moll, Dr.
        • Principal Investigator:
          • Detlev Moll, Dr.
      • Rostock, Germany, 18059
      • Ulm, Germany, 89081
        • Recruiting
        • Universitätsklinikum Ulm
        • Contact:
          • Jochen Woehrle, MD
      • Ulm, Germany, 89077
        • Active, not recruiting
        • Studienzentrum Herzklinik Ulm GbR
  • Hungary
      • Budapest, Hungary, 1115
        • Terminated
        • Szent Imre Korhaz
      • Budapest, Hungary, 1122
        • Recruiting
        • Semmelweis Egyetem
        • Contact:
          • Bela Merkely, MD
      • Budapest, Hungary, 1125
        • Terminated
        • Szent Janos Korhaz es Eszak-Budai Egyesitett Korhazak
      • Budapest, Hungary, 1134
        • Recruiting
        • Honved Korhaz
        • Contact:
          • Róbert G Kiss, MD
      • Pecs, Hungary, 7624
        • Recruiting
        • Pécsi Orvostudományi
        • Contact:
          • Kálmán Tóth, MD
      • Ózd, Hungary, 3600
        • Recruiting
        • Almási Balogh Pál Kórház
        • Contact:
          • Bélteczki János, Dr.
  • Italy
      • Rome, Italy, 00163
        • Recruiting
        • IRCCS San Raffaele Pisana (06-01)
        • Contact:
          • Maurizio Volterrani, MD
  • Poland
      • Białystok, Poland, 15-270
        • Active, not recruiting
        • Cermed Hernik (05-07)
      • Opole, Poland, 45-401
        • Not yet recruiting
        • Oddział Kardiologii Uniwersyteckiego (05-06)
        • Contact:
          • Marek Gierlotka, Prof.
        • Principal Investigator:
          • Marek Gierlotka, Prof
      • Warsaw, Poland, 04-743
        • Recruiting
        • Klinika Niewydolności Serca I Transplantologii (05-04)
        • Contact:
        • Principal Investigator:
          • Przemyslaw Leszek, Prof.
      • Warschau, Poland, 50-981
        • Recruiting
        • Wroclaw Medical University (05-01)
        • Contact:
        • Principal Investigator:
          • Ewa Jankowska, Prof.
      • Łomża, Poland, 18-404
        • Active, not recruiting
        • KLIMED Marek Klimkiewicz Lomza (05-05)
  • Portugal
      • Lisbon, Portugal, 1500-650
        • Recruiting
        • Hospital de La Luz
        • Contact:
          • Pedro Moraes Sarmento, MD
      • Lisbon, Portugal, 1649-028
        • Recruiting
        • Santa Maria University Hospital
        • Contact:
          • Dulce Brito, MD
        • Contact:
          • Fausto Pinto, MD
  • Serbia
      • Belgrad, Serbia, 11000
        • Not yet recruiting
        • Clinical Center of Serbia, Department of Cardiology
        • Contact:
        • Principal Investigator:
          • Milika Asanin
      • Belgrad, Serbia, 11000
        • Not yet recruiting
        • Clinical hospital center Zvezdara
        • Contact:
          • Goran Lončar
        • Principal Investigator:
          • Goran Lončar
      • Belgrad, Serbia, 11040
        • Not yet recruiting
        • Institute of Cardiovascular Diseases "Dedinje"
        • Contact:
          • Petar Otašević
        • Principal Investigator:
          • Petar Otašević
      • Belgrade, Serbia, 11080
        • Not yet recruiting
        • Clinical Hospital Center Zemun
        • Contact:
          • Aleksandar Nešković, Prof.
        • Principal Investigator:
          • Aleksandar Nešković, Prof.
      • Smederevo, Serbia, 11300
        • Not yet recruiting
        • General Hospital "Sveti Luka"
        • Contact:
          • Predrag Petrović
        • Principal Investigator:
          • Predrag Petrović
      • Sremska Kamenica, Serbia, 21204
        • Not yet recruiting
        • Institute for Cardiovascular Diseases of Vojvodina
        • Contact:
          • Nada Čemerlić Ađić, Prof.
        • Principal Investigator:
          • Nada Čemerlić Ađić, Prof.
  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Recruiting
        • University Medical Centre Ljubljana (07-03)
        • Contact:
          • Bojan Vrtovec, Prof.
        • Principal Investigator:
          • Bojan Vrtovec, Prof.
      • Murska Sobota, Slovenia, 9000
        • Recruiting
        • General Hospital Murska Sobota Division of Cardiology (07-01)
        • Contact:
        • Principal Investigator:
          • Mitja Lainscak, Prof
      • Topolšica, Slovenia, SI-3326
        • Recruiting
        • Hospital Topolšica (07-03)
        • Contact:
        • Principal Investigator:
          • Lucija Gaberš Parežnik, Dr
  • Spain
      • Barcelona, Spain, 08003
        • Terminated
        • Hospital del Mar (04-01)
      • Madrid, Spain, 28040
        • Not yet recruiting
        • Hospital Universitario Clinico San Carlos Madrid (04-04)
        • Contact:
          • Ramon Bover, MD
      • Málaga, Spain, 29010
        • Not yet recruiting
        • Hospital Universitarion Virgen de la Victoria (04-03)
        • Contact:
          • Jose M Garcia Pinilla, MD
      • Valencia, Spain, 46010
        • Not yet recruiting
        • Hospital Clinico Universitario Valencia (04-02)
        • Contact:
          • Julio Núñez Villota, MD
      • Valencia, Spain, 46026
        • Not yet recruiting
        • Hospital la Fe de Valencia (04-05)
        • Contact:
          • Luis Almenar Bonet, MD

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:

  1. Patients with chronic HFrEF (CHF) of at least 3 months duration and a history of documented LVEF<45%.
  2. Confirmed presence of ID (ferritin < 100 ng/mL or ferritin 100 - 299 ng/mL with TSAT < 20 %)
  3. Serum haemoglobin of 9.5 - 14.0 g/dL
  4. At time of screening considered re-stabilised and planned for discharge within next 24 h (NYHA 2 or 3), or stable ambulatory with a HF hospitalisation in the past 12 months (NYHA 2-4), or stable ambulatory with BNP > 100 pg/mL or NT-proBNP > 300 pg/mL or MR-proANP > 120 pmol/L (NYHA 2-4)
  5. Written informed consent

Exclusion Criteria:

  1. Hypersensitivity to the active substance, to FCM or any of its excipients
  2. Known serious hypersensitivity to other parenteral iron products
  3. Anaemia not attributed to iron deficiency, e.g. other microcytic anaemia
  4. Evidence of iron overload or disturbances in the utilisation of iron
  5. History of severe asthma with known FEV1 <50%
  6. Acute bacterial infection
  7. Presence of a deficiency for vitamin B12 and/or serum folate (if present, this needs to be corrected first)
  8. Use of renal replacement therapy
  9. Treatment with an erythropoietin stimulating agent (ESA), any i.v. iron and/or a blood transfusion in the previous 6 weeks prior to randomisation.
  10. More than 500 meters in the initial 6-minutes walking-test

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Verum group (FCM)
I.v. iron administration in the form of FCM will be carried out according to SmPC. I.v. iron bolus administration (1000 mg) will be followed by an optional administration of 500-1000 mg within the first 4 weeks, (up to a total of 2000 mg which is in-label), according to the approved dosing rules, followed by administration of 500 mg FCM at every 4 months, except when haemoglobin is > 16.0 g/dL or ferritin is > 800 µg/L .In the verum group, all patients will receive a saline administration, when no iron is indicated at the time of the visit and according to the values listed above.
Drug: Iron
i.v. iron administration
Placebo Comparator: Placebo group (NaCL)
Administration of i.v. NaCl at a volume according to the dosing rules for FCM, i.e. as described for the verum group.
Drug: Saline
i.v. NaCl administration
Other Names:
  • salin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Combined rate of recurrent hospitalisations for heart failure (HF) and of cardiovascular death (number of events)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Combined rate of recurrent hospitalisations for heart failure and of cardiovascular death during follow-up.
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Combined rate of recurrent cardiovascular hospitalisations and of cardiovascular death (number of events)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Combined rate of recurrent cardiovascular hospitalisations and of cardiovascular death during follow-up
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Combined rate of recurrent hospitalisations for any reason and of cardiovascular death (number of events)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Combined rate of recurrent hospitalisations for any reason and of cardiovascular death during follow-up
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Rate of recurrent cardiovascular hospitalisations (number of events)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Rate of recurrent cardiovascular hospitalisations during follow-up
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Rate of recurrent HF hospitalisations (number of events)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Rate of recurrent HF hospitalisations during follow-up
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Rate of recurrent hospitalisations of any kind (number of events)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Rate of recurrent hospitalisations of any kind during follow-up
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
All-cause mortality (number of events)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
All-cause mortality during follow-up
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
cardiovascular mortality (number of events)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
cardiovascular mortality during follow-up
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes in NYHA (New York Heart Association) functional class (scale)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes in NYHA functional class during follow-up
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes in 6-minute walk-test (nomogram)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes in 6-minute walk-test during follow-up
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes in EQ-5D (questionnaire)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes EQ-5D during follow-up
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes in Patient Global Assessment (PGA) of wellbeing (questionnaire)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes in PGA of wellbeing during follow-up
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes in renal parameters (laboratory parameters)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes in renal from baseline to end of follow-up
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes in cardiovascular parameters (laboratory parameters)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes in cardiovascular parameters from baseline to end of follow-up
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes in inflammatory parameters (laboratory parameters)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes in inflammatory parameters from baseline to end of follow-up
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes in metabolic parameters (laboratory parameters)
Time Frame: for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)
Changes in metabolic parameters from baseline to end of follow-up
for a minimum average follow-up of >2 years (We aim for a minimum follow-up of 6 months for all patients)

Collaborators and Investigators

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

Sponsor

Universitätsklinikum Hamburg-Eppendorf

Collaborators

Charite University, Berlin, Germany
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)

Investigators

  • Principal Investigator: Mahir Karaks, MD, Universitatsklinikum Hamburg-Eppendorf

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)

February 7, 2017

Primary Completion (Anticipated)

May 1, 2024

Study Completion (Anticipated)

May 1, 2024

Study Registration Dates

First Submitted

September 15, 2016

First Submitted That Met QC Criteria

January 26, 2017

First Posted (Estimate)

January 30, 2017

Study Record Updates

Last Update Posted (Estimate)

December 29, 2022

Last Update Submitted That Met QC Criteria

December 28, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FAIR-HF2
  • FAIR-HF2-DZHK5 (Other Grant/Funding Number: Deutsches Zentrum für Herzkreislaufforschung)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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