Intravenous Iron in Patients with Systolic Heart Failure and Iron Deficiency to Improve Morbidity & Mortality
- Registration Number
- NCT03036462
- Lead Sponsor
- Universitätsklinikum Hamburg-Eppendorf
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1105
- 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
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo group (NaCL) Saline Administration of i.v. NaCl at a volume according to the dosing rules for FCM, i.e. as described for the verum group. Verum group (FCM) Iron 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.
- Primary Outcome Measures
Name Time Method Time-to-first event of CV death or HF hospitalisation 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. 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.Rate of total (first and recurrent) events of hospitalisations for heart failure (HF) 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. 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.
Time-to-first event of CV death or HF hospitalisation in patients with TSAT <20% 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. 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%.
- Secondary Outcome Measures
Name Time Method Changes in 6-minute walk-test (nomogram) 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. Changes in 6-minute walk-test during follow-up
Changes in NYHA (New York Heart Association) functional class (scale) 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. Changes in NYHA functional class during follow-up
Changes in EQ-5D (questionnaire) 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. Changes EQ-5D during follow-up
Changes in Patient Global Assessment (PGA) of wellbeing (questionnaire) 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. Changes in PGA of wellbeing during follow-up
Changes in renal parameters (laboratory parameters) 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. Changes in renal parameters from baseline to end of follow-up, assessing creatinine levels
Changes in cardiovascular parameters (laboratory parameters) 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. Changes in cardiovascular parameters from baseline to end of follow-up, assessing natriuretic peptide levels
Changes in inflammatory parameters (laboratory parameters) 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. Changes in inflammatory parameters from baseline to end of follow-up, assessing C-reactive protein levels
Changes in metabolic parameters (laboratory parameters) 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. Changes in metabolic parameters from baseline to end of follow-up, assessing aspartate or alanine transaminase levels
Key Safety Endpoint: cardiovascular mortality 36 months of follow-up cardiovascular mortality during 36 months of follow-up
Key Safety Endpoint: All-cause mortality 36 months of follow-up All-cause mortality during 36 months of follow-up
Trial Locations
- Locations (51)
SLK-Kliniken Heilbronn GmbH Klinikum am Plattenwald
🇩🇪Bad Friedrichshall, Germany
Kerckhoff Klinik Bad Nauheim
🇩🇪Bad Nauheim, Germany
Universitätsmedizin Berlin Campus Benjamin Franklin
🇩🇪Berlin, Germany
Charité Berlin (Campus Virchow-Klinikum)
🇩🇪Berlin, Germany
Stiftung Bremer Herzen Bremer Institut für Herz- und Kreislauf- Forschung
🇩🇪Bremen, Germany
Herzzentrum Dresden, Universitätsklinik
🇩🇪Dresden, Germany
Uniklinik Greifswald, Klinik und Poliklinik für Innere Medizin B
🇩🇪Greifswald, Germany
Szent János kórház és Észak-budai Egyesített kórházak
🇭🇺Budapest, Hungary
Honvéd Kórház
🇭🇺Budapest, Hungary
Pécsi Orvostudományi
🇭🇺Pecs, Hungary
Almási Balogh Pál Kórház
🇭🇺Ózd, Hungary
IRCCS San Raffaele Pisana (06-01)
🇮🇹Rome, Italy
Cermed Hernik (05-07)
🇵🇱Białystok, Poland
Oddział Kardiologii Uniwersyteckiego (05-06)
🇵🇱Opole, Poland
Klinika Niewydolności Serca I Transplantologii (05-04)
🇵🇱Warsaw, Poland
Wroclaw Medical University (05-01)
🇵🇱Warschau, Poland
KLIMED Marek Klimkiewicz Lomza (05-05)
🇵🇱Łomża, Poland
Hospital de la Luz
🇵🇹Lisbon, Portugal
Santa Maria University Hospital
🇵🇹Lisbon, Portugal
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, Slovenia
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, Spain
Universitätsmedizin Göttingen
🇩🇪Göttingen, Germany
Universitätsklinikum Halle (Saale)
🇩🇪Halle, Germany
Universitärsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Cardiologicum Hamburg
🇩🇪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
LMU München Medizinische Klinik und Poliklinik 1
🇩🇪München, Germany
Klinikum rechts der Isar I. Medizinische Klinik und Poliklinik
🇩🇪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, Germany
Szent Imre Kórház
🇭🇺Budapest, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary