Clinical trial NCT03036462: Intravenous Iron in Patients With Systolic Heart Failure and Iron Deficiency to Improve Morbidity & Mortality
Official title: Ferric Carboxymaltose Assessment of Morbidity and Mortality in Patients With IRon Deficiency and Chronic Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Systolic Heart Failure
Iron Deficiency
Keywords: intravenous iron
systolic heart failure
iron deficiency
morbidity
mortality
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
name: Charite University, Berlin, Germany
First posted: 2017-01-30
Enrollment: 1105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time-to-first event of CV death or HF hospitalisation
timeFrame: 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.
measure: Rate of total (first and recurrent) events of hospitalisations for heart failure (HF)
timeFrame: 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.
measure: Time-to-first event of CV death or HF hospitalisation in patients with TSAT <20%
timeFrame: 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:
measure: Changes in 6-minute walk-test (nomogram)
timeFrame: 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.
measure: Changes in NYHA (New York Heart Association) functional class (scale)
timeFrame: 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.
measure: Changes in EQ-5D (questionnaire)
timeFrame: 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.
measure: Changes in Patient Global Assessment (PGA) of wellbeing (questionnaire)
timeFrame: 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.
measure: Changes in renal parameters (laboratory parameters)
timeFrame: 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.
measure: Changes in cardiovascular parameters (laboratory parameters)
timeFrame: 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.
measure: Changes in inflammatory parameters (laboratory parameters)
timeFrame: 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.
measure: Changes in metabolic parameters (laboratory parameters)
timeFrame: 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.
measure: Key Safety Endpoint: cardiovascular mortality
timeFrame: 36 months of follow-up
measure: Key Safety Endpoint: All-cause mortality
timeFrame: 36 months of follow-up
Other outcomes:
Locations:
city: Bad Friedrichshall
country: Germany
facility: SLK-Kliniken Heilbronn GmbH Klinikum am Plattenwald
city: Bad Nauheim
country: Germany
facility: Kerckhoff Klinik Bad Nauheim
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Charité Berlin (Campus Virchow-Klinikum)
city: Bremen
country: Germany
facility: Stiftung Bremer Herzen Bremer Institut für Herz- und Kreislauf- Forschung
city: Dresden
country: Germany
facility: Herzzentrum Dresden, Universitätsklinik
city: Greifswald
country: Germany
facility: Uniklinik Greifswald, Klinik und Poliklinik für Innere Medizin B
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale)
city: Hamburg
country: Germany
facility: Universitärsklinikum Hamburg-Eppendorf
city: Hamburg
country: Germany
facility: Cardiologicum Hamburg
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Kardiologie
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Campus Kiel
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Campus Lübeck
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim
city: Mönchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH, Innere Medizin II, Klinik für Kardiologie
city: Mühldorf
country: Germany
facility: Praxis Dr. Schön Mühldorf
city: München
country: Germany
facility: LMU München Medizinische Klinik und Poliklinik 1
city: München
country: Germany
facility: Klinikum rechts der Isar I. Medizinische Klinik und Poliklinik
city: Nürnberg
country: Germany
facility: Gemeinschaftspraxis Hagenmiller/ Jeserich
city: Nürnberg
country: Germany
facility: Universitätsklinik Medizinische Klinik 8 - Kardiologie Paracelsus Medizinische Privatuniversität Klinikum Nürnberg, Campus Süd
city: Remscheid
country: Germany
facility: KardioPrax Remscheid
city: Rostock
country: Germany
facility: Kardiologische Praxis Dr. Jens Placke
city: Ulm
country: Germany
facility: Studienzentrum Herzklinik Ulm GbR
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Budapest
country: Hungary
facility: Szent Imre Kórház
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Szent János kórház és Észak-budai Egyesített kórházak
city: Budapest
country: Hungary
facility: Honvéd Kórház
city: Pecs
country: Hungary
facility: Pécsi Orvostudományi
city: Ózd
country: Hungary
facility: Almási Balogh Pál Kórház
city: Rome
country: Italy
facility: IRCCS San Raffaele Pisana (06-01)
city: Białystok
country: Poland
facility: Cermed Hernik (05-07)
city: Opole
country: Poland
facility: Oddział Kardiologii Uniwersyteckiego (05-06)
city: Warsaw
country: Poland
facility: Klinika Niewydolności Serca I Transplantologii (05-04)
city: Warschau
country: Poland
facility: Wroclaw Medical University (05-01)
city: Łomża
country: Poland
facility: KLIMED Marek Klimkiewicz Lomza (05-05)
city: Lisbon
country: Portugal
facility: Hospital de la Luz
city: Lisbon
country: Portugal
facility: Santa Maria University Hospital
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana (07-03)
city: Murska Sobota
country: Slovenia
facility: General Hospital Murska Sobota Division of Cardiology (07-01)
city: Topolšica
country: Slovenia
facility: Hospital Topolšica (07-03)
city: Barcelona
country: Spain
facility: Hospital del Mar (04-01)
city: Madrid
country: Spain
facility: Hospital Universitario Clinico San Carlos Madrid (04-04)
city: Málaga
country: Spain
facility: Hospital Universitarion Virgen de la Victoria (04-03)
city: Valencia
country: Spain
facility: Hospital Clinico Universitario Valencia (04-02)
city: Valencia
country: Spain
facility: Hospital la Fe de Valencia (04-05)
Study officials:
affiliation: Universitätsklinikum Hamburg-Eppendorf
name: Mahir Karaks, MD
role: PRINCIPAL_INVESTIGATOR
References: