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

Universitätsklinikum Hamburg-Eppendorf1,105 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

1,105

Conditions

Systolic Heart Failure Iron Deficiency

Interventions

IronDRUG

i.v. iron administration

SalineDRUG

i.v. NaCl administration

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (51)

Outcomes

Primary Outcomes

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.

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.

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.

Time frame: 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.

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

Time frame: 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

Changes in 6-minute walk-test (nomogram)

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

Time frame: 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.

Data from ClinicalTrials.gov

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