Iron in Patients With Cardiovascular Disease (iCHF-2)

Investigator-initiated, Randomized, Double-blind, Controlled, Multi-center Trial of Intravenous Iron in Patients With Cardiovascular Disease and Concomitant Iron Deficiency

It is now recognized that iron deficiency in cardiovascular disease contributes to impaired clinical outcome.

Study Overview

• Status: Terminated
• Conditions: Cardiovascular Diseases; Atrial Fibrillation; Acute Myocardial Infarction; Systolic Heart Failure; Anemia, Iron-deficiency
• Intervention / Treatment: Drug: Ferric carboxymaltose; Drug: Saline

Detailed Description

The clinical trial is designed as a prospective, multi-centre, double-blind, randomised, controlled, interventional trial to investigate whether a therapy with i.v. iron (iron carboxymaltose) compared to saline can improve functional status across a subset of cardiovascular disease -namely acute myocardial infarction, atrial fibrillation, and heart failure with reduced ejection fraction.

Iron administration will be carried out according to summary of product characteristics. 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 iron carboxymaltose (over 15 minutes), except when haemoglobin is > 16.0 g/dL or ferritin is > 600 µg/L.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12203
    • University of Berlin, Campus Benjamin-Franklin
  • Hamburg, Germany, 20246
    • University Heart Center Hamburg
  • Ulm, Germany, 89081
    • University of Ulm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Cohort A (acute myocardial infarction): Acute Myocardial Infarction within 10 days (randomization/ first iron supplementation/ MRI must be performed within 10 days after AMI), without prior heart failure (defined as any known previous report of LVEF ≤ 45%) Cohort B (atrial fibrillation): Paroxysmal Atrial fibrillation or persistent AF Cohort C (heart failure): Left-ventricular ejection fraction ≤ 45 % (documented within the last 12 months prior to screening), all NYHA classes allowed
2. Confirmed presence of iron deficiency (ferritin < 100 ng/mL or ferritin 100 - 299 ng/mL with transferrin saturation < 20 %)
3. Haemoglobin ≤ 15.5 g/dL
4. Written informed consent

Exclusion Criteria:

1. Evidence of iron overload or disturbances in the utilisation of iron
2. History of severe asthma, eczema or other atopic allergy
3. History of immune or inflammatory conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis)
4. Use of renal replacement therapy
5. Treatment with an erythropoietin stimulating agent (ESA), any i.v. iron and/or a blood transfusion in the previous 4 weeks prior to randomisation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous iron; Intravenous iron administration in the form of ferric carboxymaltose will be carried out according to summary of product characteristics. 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 ferric carboxymaltose at months 4 and 8, except when haemoglobin is > 16.0 g/dL or ferritin is > 600 µg/L. To avoid unblinding in these patients a saline infusion will be administered.	Drug: Ferric carboxymaltose; Intravenous iron
Placebo Comparator: Placebo; Administration of i.v. NaCl according to the dosing rules for intravenous iron.	Drug: Saline; Saline application according to dosing rules of iron.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort A: Left-ventricular ejection fraction	Change from baseline to week 16 in left-ventricular ejection fraction as determined by cardiac-MRI	16 weeks
Cohort B: Burden of atrial fibrillation	Delta between treatment groups in burden of atrial fibrillation from day 90 to 365 as assessed by a routinely implanted event recorder.	12 months
Cohort C: Left-ventricular ejection fraction	Change from baseline to week 16 in left-ventricular ejection fraction as determined by cardiac-MRI.	16 weeks

Collaborators and Investigators

• Sponsor: Dr. med. Mahir Karakas
• Investigators: Principal Investigator: Mahir Karakas, MD, MBA, University Heart Center Hamburg

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2019
• Primary Completion (Actual): December 15, 2021
• Study Completion (Actual): December 15, 2021

Study Registration Dates

• First Submitted: June 17, 2019
• First Submitted That Met QC Criteria: June 17, 2019
• First Posted (Actual): June 19, 2019

Study Record Updates

• Last Update Posted (Estimated): December 27, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Atrial fibrillation; Anemia; Iron deficiency; Acute myocardial infarction; Systolic heart failure
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Vascular Diseases; Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Arrhythmias, Cardiac; Heart Murmurs; Myocardial Infarction; Infarction; Heart Failure; Cardiovascular Diseases; Anemia, Iron-Deficiency; Atrial Fibrillation; Systolic Murmurs; Heart Failure, Systolic; Iron Deficiencies
• Other Study ID Numbers: iCHF-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No