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

Iron Deficiency Clinical Trial

— FAIR-HF2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03036462
• Other study ID #: FAIR-HF2
• Secondary ID: FAIR-HF2-DZHK5
• Status: Completed
• Phase: Phase 4
• Start date: February 7, 2017
• Est. completion date: May 2, 2024

Study information

• Verified date: May 2024
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1120
• Est. completion date: May 2, 2024
• Est. primary completion date: May 2, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Heart Failure
• Heart Failure, Systolic
• Iron Deficiency
• Systolic Heart Failure
• Systolic Murmurs

Intervention

Drug:
• Iron
i.v. iron administration
• Saline
i.v. NaCl administration

Locations

Country	Name	City	State
Germany	SLK-Kliniken Heilbronn GmbH Klinikum am Plattenwald	Bad Friedrichshall
Germany	Kerckhoff Klinik Bad Nauheim	Bad Nauheim
Germany	Charité Berlin (Campus Virchow-Klinikum)	Berlin
Germany	Universitätsmedizin Berlin Campus Benjamin Franklin	Berlin
Germany	Stiftung Bremer Herzen Bremer Institut für Herz- und Kreislauf- Forschung	Bremen
Germany	Herzzentrum Dresden, Universitätsklinik	Dresden
Germany	Universitätsmedizin Göttingen	Göttingen
Germany	Uniklinik Greifswald, Klinik und Poliklinik für Innere Medizin B	Greifswald
Germany	Universitätsklinikum Halle (Saale)	Halle
Germany	Cardiologicum Hamburg	Hamburg
Germany	Universitärsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum des Saarlandes	Homburg
Germany	Universitätsklinikum Jena, Kardiologie	Jena
Germany	Universitätsklinikum Schleswig-Holstein Campus Kiel	Kiel
Germany	Universitätsklinikum Schleswig-Holstein Campus Lübeck	Lübeck
Germany	Universitätsklinikum Magdeburg	Magdeburg
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Universitätsmedizin Mannheim	Mannheim
Germany	Kliniken Maria Hilf GmbH, Innere Medizin II, Klinik für Kardiologie	Mönchengladbach
Germany	Praxis Dr. Schön Mühldorf	Mühldorf
Germany	Klinikum rechts der Isar I. Medizinische Klinik und Poliklinik	München
Germany	LMU München Medizinische Klinik und Poliklinik 1	München
Germany	Gemeinschaftspraxis Hagenmiller/ Jeserich	Nürnberg
Germany	Universitätsklinik Medizinische Klinik 8 - Kardiologie Paracelsus Medizinische Privatuniversität Klinikum Nürnberg, Campus Süd	Nürnberg
Germany	KardioPrax Remscheid	Remscheid
Germany	Kardiologische Praxis Dr. Jens Placke	Rostock
Germany	Studienzentrum Herzklinik Ulm GbR	Ulm
Germany	Universitätsklinikum Ulm	Ulm
Hungary	Honvéd Kórház	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Szent Imre Kórház	Budapest
Hungary	Szent János kórház és Észak-budai Egyesített kórházak	Budapest
Hungary	Almási Balogh Pál Kórház	Ózd
Hungary	Pécsi Orvostudományi	Pecs
Italy	IRCCS San Raffaele Pisana (06-01)	Rome
Poland	Cermed Hernik (05-07)	Bialystok
Poland	KLIMED Marek Klimkiewicz Lomza (05-05)	Lomza
Poland	Oddzial Kardiologii Uniwersyteckiego (05-06)	Opole
Poland	Klinika Niewydolnosci Serca I Transplantologii (05-04)	Warsaw
Poland	Wroclaw Medical University (05-01)	Warschau
Portugal	Hospital de la Luz	Lisbon
Portugal	Santa Maria University Hospital	Lisbon
Serbia	Clinical Center of Serbia, Department of Cardiology	Belgrad
Serbia	Clinical Hospital Center Zvezdara	Belgrad
Serbia	Institute of Cardiovascular Diseases "Dedinje"	Belgrad
Serbia	Clinical Hospital Center Zemun	Belgrade
Serbia	General Hospital "Sveti Luka"	Smederevo
Serbia	Institute for Cardiovascular Diseases of Vojvodina	Sremska Kamenica
Slovenia	University Medical Centre Ljubljana (07-03)	Ljubljana
Slovenia	General Hospital Murska Sobota Division of Cardiology (07-01)	Murska Sobota
Slovenia	Hospital Topolšica (07-03)	Topolšica
Spain	Hospital del Mar (04-01)	Barcelona
Spain	Hospital Universitario Clinico San Carlos Madrid (04-04)	Madrid
Spain	Hospital Universitarion Virgen de la Victoria (04-03)	Málaga
Spain	Hospital Clinico Universitario Valencia (04-02)	Valencia
Spain	Hospital la Fe de Valencia (04-05)	Valencia

Sponsors (3)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf	Charite University, Berlin, Germany, Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)

Countries where clinical trial is conducted

Germany,  Hungary,  Italy,  Poland,  Portugal,  Serbia,  Slovenia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Combined rate of recurrent hospitalisations for heart failure (HF) and of cardiovascular death (number of events)	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	Combined rate of recurrent cardiovascular hospitalisations and of cardiovascular death (number of events)	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)
Secondary	Combined rate of recurrent hospitalisations for any reason and of cardiovascular death (number of events)	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)
Secondary	Rate of recurrent cardiovascular hospitalisations (number of events)	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)
Secondary	Rate of recurrent HF hospitalisations (number of events)	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)
Secondary	Rate of recurrent hospitalisations of any kind (number of events)	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)
Secondary	All-cause mortality (number of events)	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)
Secondary	cardiovascular mortality (number of events)	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)
Secondary	Changes in NYHA (New York Heart Association) functional class (scale)	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)
Secondary	Changes in 6-minute walk-test (nomogram)	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)
Secondary	Changes in EQ-5D (questionnaire)	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)
Secondary	Changes in Patient Global Assessment (PGA) of wellbeing (questionnaire)	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)
Secondary	Changes in renal parameters (laboratory parameters)	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)
Secondary	Changes in cardiovascular parameters (laboratory parameters)	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)
Secondary	Changes in inflammatory parameters (laboratory parameters)	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)
Secondary	Changes in metabolic parameters (laboratory parameters)	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)