AzTrials
AzTrials

Systolic Heart FailurePhase 4FAIR-HF2NCT03036462

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

A Phase 4 study testing Iron and Saline in people with Systolic Heart Failure and Iron Deficiency, run by Universitätsklinikum Hamburg-Eppendorf at 51 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to determine whether intravenous iron supplementation using ferric carboxymaltosis (FCM) extends the time-to-first-event of heart failure hospitalisations and cardiovascular (CV) death and reduces hospitalisation and mortality in patients with iron deficiency and heart failure. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Systolic Heart Failure, Iron Deficiency
What is being tested?
Iron and Saline
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,105 participants
Where
51 sitesin 7 countries
Study dates
7 Mar 2017to 2 May 2024
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with chronic HFrEF (CHF) of at least 3 months duration and a history of documented LVEF<45%.
  • Confirmed presence of ID (ferritin < 100 ng/mL or ferritin 100 - 299 ng/mL with TSAT < 20 %)
  • Serum haemoglobin of 9.5 - 14.0 g/dL
  • 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)
  • Written informed consent

Who cannot join

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

Trial locations and contacts

51 sites in 7 countries.

51 sites in 7 countries

Germany29 sites

  • SLK-Kliniken Heilbronn GmbH Klinikum am Plattenwald

    Bad Friedrichshall, 74177

  • Kerckhoff Klinik Bad Nauheim

    Bad Nauheim, 61231

  • Universitätsmedizin Berlin Campus Benjamin Franklin

    Berlin, 12203

  • Charité Berlin (Campus Virchow-Klinikum)

    Berlin, 13353

  • Stiftung Bremer Herzen Bremer Institut für Herz- und Kreislauf- Forschung

    Bremen, 28277

  • Herzzentrum Dresden, Universitätsklinik

    Dresden, 01307

  • Universitätsmedizin Göttingen

    Göttingen, 37075

  • Uniklinik Greifswald, Klinik und Poliklinik für Innere Medizin B

    Greifswald, 17475

  • Universitätsklinikum Halle (Saale)

    Halle, 06120

  • Cardiologicum Hamburg

    Hamburg, Free and Hanseatic City of Hamburg, 22041

  • Universitärsklinikum Hamburg-Eppendorf

    Hamburg, 20251

  • Universitätsklinikum Heidelberg

    Heidelberg, 69120

  • Universitätsklinikum des Saarlandes

    Homburg, 66421

  • Universitätsklinikum Jena, Kardiologie

    Jena, 07747

  • Universitätsklinikum Schleswig-Holstein Campus Kiel

    Kiel, 24105

  • Universitätsklinikum Schleswig-Holstein Campus Lübeck

    Lübeck, 23538

  • Universitätsklinikum Magdeburg

    Magdeburg, 39120

  • Universitätsmedizin der Johannes Gutenberg-Universität Mainz

    Mainz, 55131

  • Universitätsmedizin Mannheim

    Mannheim, 68167

  • Kliniken Maria Hilf GmbH, Innere Medizin II, Klinik für Kardiologie

    Mönchengladbach, 41063

  • Praxis Dr. Schön Mühldorf

    Mühldorf, 84453

  • LMU München Medizinische Klinik und Poliklinik 1

    München, 81377

  • Klinikum rechts der Isar I. Medizinische Klinik und Poliklinik

    München, 81675

  • Gemeinschaftspraxis Hagenmiller/ Jeserich

    Nuremberg, 90402

  • Universitätsklinik Medizinische Klinik 8 - Kardiologie Paracelsus Medizinische Privatuniversität Klinikum Nürnberg, Campus Süd

    Nuremberg, 90471

  • KardioPrax Remscheid

    Remscheid, 42853

  • Kardiologische Praxis Dr. Jens Placke

    Rostock, 18059

  • Studienzentrum Herzklinik Ulm GbR

    Ulm, 89077

  • Universitätsklinikum Ulm

    Ulm, 89081

Other trials in Germany

Hungary6 sites

  • Szent Imre Kórház

    Budapest, 1115

  • Semmelweis Egyetem

    Budapest, 1122

  • Szent János kórház és Észak-budai Egyesített kórházak

    Budapest, 1125

  • Honvéd Kórház

    Budapest, 1134

  • Almási Balogh Pál Kórház

    Ózd, 3600

  • Pécsi Orvostudományi

    Pécs, 7624

Other trials in Hungary

Poland5 sites

  • Cermed Hernik (05-07)

    Bialystok, 15-270

  • KLIMED Marek Klimkiewicz Lomza (05-05)

    Łomża, 18-404

  • Oddział Kardiologii Uniwersyteckiego (05-06)

    Opole, 45-401

  • Klinika Niewydolności Serca I Transplantologii (05-04)

    Warsaw, 04-743

  • Wroclaw Medical University (05-01)

    Warsaw, 50-981

Other trials in Poland

Spain5 sites

  • Hospital del Mar (04-01)

    Barcelona, 08003

  • Hospital Universitario Clinico San Carlos Madrid (04-04)

    Madrid, 28040

  • Hospital Universitarion Virgen de la Victoria (04-03)

    Málaga, 29010

  • Hospital Clinico Universitario Valencia (04-02)

    Valencia, 46010

  • Hospital la Fe de Valencia (04-05)

    Valencia, 46026

Other trials in Spain

Slovenia3 sites

  • University Medical Centre Ljubljana (07-03)

    Ljubljana, 1000

  • General Hospital Murska Sobota Division of Cardiology (07-01)

    Murska Sobota, 9000

  • Hospital Topolšica (07-03)

    Topolšica, SI-3326

Other trials in Slovenia

Portugal2 sites

  • Hospital de la Luz

    Lisbon, 1500-650

  • Santa Maria University Hospital

    Lisbon, 1649-028

Other trials in Portugal

Italy1 site

  • IRCCS San Raffaele Pisana (06-01)

    Rome, 00163

Other trials in Italy

About this study

Official title: Ferric Carboxymaltose Assessment of Morbidity and Mortality in Patients With IRon Deficiency and Chronic Heart Failure

The purpose of this study is to determine whether intravenous iron supplementation using ferric carboxymaltosis (FCM) extends the time-to-first-event of heart failure hospitalisations and cardiovascular (CV) death and reduces hospitalisation and mortality in patients with iron deficiency and heart failure.

Read the 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 extend the time-to-first-event of heart failure hospitalisations and cardiovascular (CV) death (in the full population and in the population of patients with TSAT<20%) and reduce the rate of recurrent events of heart failure hospitalisations.

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.

Being tested
Iron, Saline
Keywords
intravenous iron, systolic heart failure, iron deficiency, morbidity, mortality
Medical subject headings
Heart Failure, Systolic, Iron Deficiencies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IronDrug

    i.v. iron administration

  • SalineDrug

    Also called salin

    i.v. NaCl administration

Study groups in NCT03036462
Study groupRoleWhat they receive
Verum group (FCM)ExperimentalI.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.
Receives: Drug: Iron
Placebo group (NaCL)Placebo comparatorAdministration of i.v. NaCl at a volume according to the dosing rules for FCM, i.e. as described for the verum group.
Receives: Drug: Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time-to-first event of CV death or HF hospitalisation

    Show that treatment of patients with systolic heart failure (HF) and iron deficiency (ID) with i.v. iron (Ferric Carboxymaltose, FCM) versus placebo (i.v. NaCl) can extend the time-to-first-event of heart failure hospitalisations and cardiovascular (CV) death.

    Type I error rate control across the three primary endpoints will be ensured by using the Hochberg procedure.

    Measured: The whole follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.

  2. Rate of total (first and recurrent) events of hospitalisations for heart failure (HF)

    Show that treatment of patients with systolic heart failure (HF) and iron deficiency (ID) with i.v. iron (Ferric Carboxymaltose, FCM) versus placebo (i.v. NaCl) reduces the rate of recurrent events of heart failure hospitalisations.

    Measured: The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.

  3. Time-to-first event of CV death or HF hospitalisation in patients with TSAT <20%

    Show that treatment of patients with systolic heart failure (HF) and iron deficiency (ID) with i.v. iron (Ferric Carboxymaltose, FCM) versus placebo (i.v. NaCl) can extend the time-to-first-event of heart failure hospitalisations and cardiovascular (CV) death in the population of patients with TSAT<20%.

    Measured: During the wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.

Secondary outcomes (10)

  1. Changes in 6-minute walk-test (nomogram)

    Changes in 6-minute walk-test during follow-up

    Measured: The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.

  2. Changes in NYHA (New York Heart Association) functional class (scale)

    Changes in NYHA functional class during follow-up

    Measured: The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.

  3. Changes in EQ-5D (questionnaire)

    Changes EQ-5D during follow-up

    Measured: The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.

  4. Changes in Patient Global Assessment (PGA) of wellbeing (questionnaire)

    Changes in PGA of wellbeing during follow-up

    Measured: The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.

  5. Changes in renal parameters (laboratory parameters)

    Changes in renal parameters from baseline to end of follow-up, assessing creatinine levels

    Measured: The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.

  6. Changes in cardiovascular parameters (laboratory parameters)

    Changes in cardiovascular parameters from baseline to end of follow-up, assessing natriuretic peptide levels

    Measured: The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.

  7. Changes in inflammatory parameters (laboratory parameters)

    Changes in inflammatory parameters from baseline to end of follow-up, assessing C-reactive protein levels

    Measured: The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.

  8. Changes in metabolic parameters (laboratory parameters)

    Changes in metabolic parameters from baseline to end of follow-up, assessing aspartate or alanine transaminase levels

    Measured: The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.

  9. Key Safety Endpoint: cardiovascular mortality

    cardiovascular mortality during 36 months of follow-up

    Measured: 36 months of follow-up

  10. Key Safety Endpoint: All-cause mortality

    All-cause mortality during 36 months of follow-up

    Measured: 36 months of follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jan 2017 (estimated)
  2. Study start7 Mar 2017
  3. Primary completion2 May 2024
  4. Study completion2 May 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
1,105 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03036462
Sponsor's protocol ID
FAIR-HF2
Other IDs
FAIR-HF2-DZHK5
Acronym
FAIR-HF2
Status last verified
Jan 2025
First submitted
15 Sep 2016
Last updated
28 Jan 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Karakas M, Friede T, Butler J, Talha KM, Placzek M, Asendorf T, Diek M, Nosko A, Stas A, Kluge S, Jarczak D, DeHeer G, Rybczynski M, Bayes-Genis A, Bohm M, Coats AJS, Edelmann F, Filippatos G, Hasenfuss G, Haverkamp W, Lainscak M, Landmesser U, Macdougall IC, Merkely B, Pieske BM, Pinto FJ, Rassaf T, Visser-Rogers JK, Rosano G, Volterrani M, von Haehling S, Anker MS, Doehner W, Ince H, Koehler F, Savarese G, Khan MS, Krohnert UR, Gori T, Trenkwalder T, Akin I, Paitazoglou C, Kobielusz-Gembala I, Kuthi L, Frey N, Licka M, Kaab S, Laugwitz KL, Ponikowski P, Anker SD. Intravenous ferric carboxymaltose in heart failure with iron deficiency (FAIR-HF2 DZHK05 trial): Sex-specific outcomes. Eur J Heart Fail. 2025 Nov;27(11):2328-2342. doi: 10.1002/ejhf.3742. Epub 2025 Jul 31.

    PubMed 40740027

  • Anker SD, Friede T, Butler J, Talha KM, Placzek M, Diek M, Nosko A, Stas A, Kluge S, Jarczak D, Deheer G, Rybczynski M, Bayes-Genis A, Edelmann F, Filippatos G, Hasenfuss G, Haverkamp W, Lainscak M, Landmesser U, Macdougall IC, Merkely B, Pieske BM, Pinto FJ, Rassaf T, Volterrani M, von Haehling S, Anker MS, Doehner W, Ince H, Koehler F, Savarese G, Rauch-Krohnert U, Gori T, Trenkwalder T, Akin I, Paitazoglou C, Kobielusz-Gembala I, Zmuda W, Kuthi L, Frey N, Licka M, Kaab S, Laugwitz KL, Ponikowski P, Karakas M. Ferric carboxymaltose assessment of morbidity and mortality in patients with iron deficiency and chronic heart failure (FAIR-HF2-DZHK05) trial: Baseline characteristics and comparison to other relevant clinical trials. Eur J Heart Fail. 2025 Aug;27(8):1436-1443. doi: 10.1002/ejhf.3658. Epub 2025 Apr 29.

    PubMed 40300786

  • Anker SD, Friede T, Butler J, Talha KM, Placzek M, Diek M, Nosko A, Stas A, Kluge S, Jarczak D, deHeer G, Rybczynski M, Bayes-Genis A, Bohm M, Coats AJS, Edelmann F, Filippatos G, Hasenfuss G, Haverkamp W, Lainscak M, Landmesser U, Macdougall IC, Merkely B, Pieske BM, Pinto FJ, Rassaf T, Visser-Rogers JK, Rosano G, Volterrani M, von Haehling S, Anker MS, Doehner W, Ince H, Koehler F, Savarese G, Khan MS, Rauch-Krohnert U, Gori T, Trenkwalder T, Akin I, Paitazoglou C, Kobielusz-Gembala I, Kuthi L, Frey N, Licka M, Kaab S, Laugwitz KL, Ponikowski P, Karakas M. Intravenous Ferric Carboxymaltose in Heart Failure With Iron Deficiency: The FAIR-HF2 DZHK05 Randomized Clinical Trial. JAMA. 2025 Jun 10;333(22):1965-1976. doi: 10.1001/jama.2025.3833.

    PubMed 40159390

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Iron and Saline in people with Systolic Heart Failure and Iron Deficiency, run by Universitätsklinikum Hamburg-Eppendorf at 51 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 51 sites in Germany, Hungary, Poland, Spain, Slovenia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time-to-first event of CV death or HF hospitalisation (time frame: The whole follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03036462, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in