Effect of Intravenous FerRic carbOxymaltose oN Reverse Remodeling Following Cardiac Resynchronization Therapy (IRON-CRT)

To assess impact on left ventricular reverse remodeling defined as a change in left ventricular ejection fraction in heart failure patients with reduced ejection fraction (and previous implantation of cardiac resynchronization therapy) undergoing treatment with ferric carboxymaltose vs. placebo

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Ferric Carboxymaltose; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Limburg
    • Genk, Limburg, Belgium, 3500
      • Pieter Martens

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Chronic heart failure and implantation of cardiac resynchronization therapy more than 6 months ago and presence of iron deficiency (ferritin < 100 μg/l, irrespective of TSAT or ferritine between 100 - 300 μg/l with TSAT < 20%) and presence of incomplete reverse remodeling (LVEF < 40%).
2. Age ≥18 years
3. Obtained informed consent
4. Stable pharmacological therapy of heart failure during the last 4 weeks (with the exception of diuretics)

Exclusion Criteria:

1. Hemochromatosis, iron overload, defined as TSAT > 45%
2. Hemoglobin > 15 g/dl at inclusion
3. Known hypersensitivity to injectafer®.
4. Known active infection, CRP>20 mg/L, clinically significant bleeding, active malignancy.
5. Chronic liver disease and/or screening alanine transaminase (ALT) or aspartate transaminase (AST) above three times the upper limit of the normal range.
6. Immunosuppressive therapy or renal dialysis (current or planned within the next 6 months).
7. History of erythropoietin, i. v. or oral iron therapy, and blood transfusion in previous 12 weeks and/or such therapy planned within the next 6 months.
8. Unstable angina pectoris as judged by the investigator, clinically significant uncorrected valvular disease or left ventricular outflow obstruction, obstructive cardiomyopathy, poorly controlled fast atrial fibrillation or flutter, poorly controlled symptomatic brady- or tachyarrhythmias.
9. Acute myocardial infarction or acute coronary syndrome, transient ischemic attack or stroke within the last 3 months.
10. Coronary-artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, aortic; diagnostic catheters are allowed) or major surgery, including thoracic and cardiac surgery, within the last 3 months.
11. Inability to fully comprehend and/or perform study procedures in the investigator's opinion.
12. Vitamin B12 and/or serum folate deficiency according to the laboratory (re-screening is possible after substitution therapy).
13. Pregnancy or lactation.
14. Participation in another clinical trial within previous 30 days and/or anticipated participation in another trial during this study.
15. Planned cardiac hospitalization during study follow-up

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: Ferric carboxymaltose; Ferric carboxymaltose according to SmPC	Drug: Ferric Carboxymaltose; Ferric carboxymaltose will be administered according to product specification dosing; Other Names: injectafer
Placebo Comparator: Placebo; Normal saline (0.9%)	Drug: Placebo; IV nacl 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in left ventricular ejection fraction from baseline	delta_LVEF measured by 3D-echocardiography	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in left ventricular end systolic volume from baseline	delta_LVESV measured by 3D-echocardiography	3 months
Change in left ventricular end diastolic volume from baseline	delta_LVEDV measured by 3D-echocardiography	3 months
Force frequency relationship	measured by 2D-echocardiography	3 months
Heart failure hospitalization and all-cause mortality	measured by telephone contact	Up to six months
Incidence of Treatment-associated Serious and non-serious adverse events.	Serious and non-serious adverse events (AE) will be registered, which include:start date AE, duration AE, end-date AE, treatment group, continuation of AE after dose interruption, causality with study medication, presence of risk factors for AE and response to AE (sequela or recovery).	During intravenous study drug administration and 1-hour in hospital follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predefined right ventricular (RV) analysis	Assessment of effect of FCM on RV-function at rest and during incremental pacing. Assessment of RV-to-pulmonary artery coupling	3 months

Collaborators and Investigators

• Sponsor: Hasselt University
• Collaborators: Ziekenhuis Oost-Limburg

Publications and helpful links

General Publications

• Martens P, Dupont M, Dauw J, Nijst P, Herbots L, Dendale P, Vandervoort P, Bruckers L, Tang WHW, Mullens W. The effect of intravenous ferric carboxymaltose on cardiac reverse remodelling following cardiac resynchronization therapy-the IRON-CRT trial. Eur Heart J. 2021 Dec 21;42(48):4905-4914. doi: 10.1093/eurheartj/ehab411.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): August 4, 2021

Study Registration Dates

• First Submitted: November 2, 2017
• First Submitted That Met QC Criteria: December 20, 2017
• First Posted (Actual): December 21, 2017

Study Record Updates

• Last Update Posted (Actual): August 11, 2021
• Last Update Submitted That Met QC Criteria: August 4, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: IRON-CRT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Yes, full patient level data

Drug and device information, study documents

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