Clinical trial NCT03380520: Effect of Intravenous FerRic carbOxymaltose oN Reverse Remodeling Following Cardiac Resynchronization Therapy
Official title: Effect of Intravenous FerRic carbOxymaltose oN Reverse Remodeling Following Cardiac Resynchronization Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure
Lead sponsor: Hasselt University
Sponsor class: OTHER
Collaborators: name: Ziekenhuis Oost-Limburg
First posted: 2017-12-21
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Change in left ventricular ejection fraction from baseline
timeFrame: 3 months
Secondary outcomes:
measure: Change in left ventricular end systolic volume from baseline
timeFrame: 3 months
measure: Change in left ventricular end diastolic volume from baseline
timeFrame: 3 months
measure: Force frequency relationship
timeFrame: 3 months
measure: Heart failure hospitalization and all-cause mortality
timeFrame: Up to six months
measure: Incidence of Treatment-associated Serious and non-serious adverse events.
timeFrame: During intravenous study drug administration and 1-hour in hospital follow-up
Other outcomes:
measure: Predefined right ventricular (RV) analysis
timeFrame: 3 months
Locations:
city: Genk
country: Belgium
facility: Pieter Martens
state: Limburg
Study officials:
References:
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.