Effect of Intravenous FerRic carbOxymaltose oN Reverse Remodeling Following Cardiac Resynchronization Therapy (IRON-CRT)
Primary Purpose
Heart Failure
Status
Completed
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Ferric Carboxymaltose
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure
Eligibility Criteria
Inclusion Criteria:
- 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%).
- Age ≥18 years
- Obtained informed consent
- Stable pharmacological therapy of heart failure during the last 4 weeks (with the exception of diuretics)
Exclusion Criteria:
- Hemochromatosis, iron overload, defined as TSAT > 45%
- Hemoglobin > 15 g/dl at inclusion
- Known hypersensitivity to injectafer®.
- Known active infection, CRP>20 mg/L, clinically significant bleeding, active malignancy.
- Chronic liver disease and/or screening alanine transaminase (ALT) or aspartate transaminase (AST) above three times the upper limit of the normal range.
- Immunosuppressive therapy or renal dialysis (current or planned within the next 6 months).
- 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.
- 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.
- Acute myocardial infarction or acute coronary syndrome, transient ischemic attack or stroke within the last 3 months.
- 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.
- Inability to fully comprehend and/or perform study procedures in the investigator's opinion.
- Vitamin B12 and/or serum folate deficiency according to the laboratory (re-screening is possible after substitution therapy).
- Pregnancy or lactation.
- Participation in another clinical trial within previous 30 days and/or anticipated participation in another trial during this study.
- Planned cardiac hospitalization during study follow-up
Sites / Locations
- Pieter Martens
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Ferric carboxymaltose
Placebo
Arm Description
Ferric carboxymaltose according to SmPC
Normal saline (0.9%)
Outcomes
Primary Outcome Measures
Change in left ventricular ejection fraction from baseline
delta_LVEF measured by 3D-echocardiography
Secondary Outcome Measures
Change in left ventricular end systolic volume from baseline
delta_LVESV measured by 3D-echocardiography
Change in left ventricular end diastolic volume from baseline
delta_LVEDV measured by 3D-echocardiography
Force frequency relationship
measured by 2D-echocardiography
Heart failure hospitalization and all-cause mortality
measured by telephone contact
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).
Full Information
NCT ID
NCT03380520
First Posted
November 2, 2017
Last Updated
August 4, 2021
Sponsor
Hasselt University
Collaborators
Ziekenhuis Oost-Limburg
1. Study Identification
Unique Protocol Identification Number
NCT03380520
Brief Title
Effect of Intravenous FerRic carbOxymaltose oN Reverse Remodeling Following Cardiac Resynchronization Therapy
Acronym
IRON-CRT
Official Title
Effect of Intravenous FerRic carbOxymaltose oN Reverse Remodeling Following Cardiac Resynchronization Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
October 1, 2017 (Actual)
Primary Completion Date
December 31, 2020 (Actual)
Study Completion Date
August 4, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hasselt University
Collaborators
Ziekenhuis Oost-Limburg
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
75 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ferric carboxymaltose
Arm Type
Experimental
Arm Description
Ferric carboxymaltose according to SmPC
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Normal saline (0.9%)
Intervention Type
Drug
Intervention Name(s)
Ferric Carboxymaltose
Other Intervention Name(s)
injectafer
Intervention Description
Ferric carboxymaltose will be administered according to product specification dosing
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
IV nacl 0.9%
Primary Outcome Measure Information:
Title
Change in left ventricular ejection fraction from baseline
Description
delta_LVEF measured by 3D-echocardiography
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Change in left ventricular end systolic volume from baseline
Description
delta_LVESV measured by 3D-echocardiography
Time Frame
3 months
Title
Change in left ventricular end diastolic volume from baseline
Description
delta_LVEDV measured by 3D-echocardiography
Time Frame
3 months
Title
Force frequency relationship
Description
measured by 2D-echocardiography
Time Frame
3 months
Title
Heart failure hospitalization and all-cause mortality
Description
measured by telephone contact
Time Frame
Up to six months
Title
Incidence of Treatment-associated Serious and non-serious adverse events.
Description
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).
Time Frame
During intravenous study drug administration and 1-hour in hospital follow-up
Other Pre-specified Outcome Measures:
Title
Predefined right ventricular (RV) analysis
Description
Assessment of effect of FCM on RV-function at rest and during incremental pacing. Assessment of RV-to-pulmonary artery coupling
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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%).
Age ≥18 years
Obtained informed consent
Stable pharmacological therapy of heart failure during the last 4 weeks (with the exception of diuretics)
Exclusion Criteria:
Hemochromatosis, iron overload, defined as TSAT > 45%
Hemoglobin > 15 g/dl at inclusion
Known hypersensitivity to injectafer®.
Known active infection, CRP>20 mg/L, clinically significant bleeding, active malignancy.
Chronic liver disease and/or screening alanine transaminase (ALT) or aspartate transaminase (AST) above three times the upper limit of the normal range.
Immunosuppressive therapy or renal dialysis (current or planned within the next 6 months).
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.
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.
Acute myocardial infarction or acute coronary syndrome, transient ischemic attack or stroke within the last 3 months.
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.
Inability to fully comprehend and/or perform study procedures in the investigator's opinion.
Vitamin B12 and/or serum folate deficiency according to the laboratory (re-screening is possible after substitution therapy).
Pregnancy or lactation.
Participation in another clinical trial within previous 30 days and/or anticipated participation in another trial during this study.
Planned cardiac hospitalization during study follow-up
Facility Information:
Facility Name
Pieter Martens
City
Genk
State/Province
Limburg
ZIP/Postal Code
3500
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
Yes, full patient level data
Citations:
PubMed Identifier
34185066
Citation
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.
Results Reference
result
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Effect of Intravenous FerRic carbOxymaltose oN Reverse Remodeling Following Cardiac Resynchronization Therapy
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