Phase IV, open-label, randomized clinical trial on the effect of intravenous iron on quality of life in elderly patients with Acute Coronary Syndrome.

The primary objective is to determine whether patients aged 65 years or older with iron deficiency following an acute coronary syndrome who receive intravenous iron treatment demonstrate improved quality of life at 6 and 12 months of follow-up compared to untreated patients. This objective addresses the clinical relevance of correcting iron deficiency in elderly post-ACS populations, where quality of life outcomes are significant indicators of therapeutic benefit.

The secondary objectives include:

• Evaluation of the impact of iron deficiency correction on frailty, risk of heart failure decompensation, reinfarction, stroke, and all-cause mortality at baseline, 6 months, and 12 months of follow-up.

• Assessment of differences in extended iron profile and inflammatory mediators between treated and untreated patient subgroups at 12 months compared to baseline levels.

• Comparison of variation in biological age between patient subgroups with and without intravenous iron treatment at 12 months of follow-up.

• Assessment of telomere shortening differences between treated and untreated patient subgroups at 12 months compared to baseline results.

• Analysis of the correlation between baseline levels of Klotho and FGF23 with biological age, telomere length, and inflammatory profile in patient subgroups with and without intravenous iron treatment at baseline and 12 months of follow-up.

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population consists of patients aged **65 years or older** who have been diagnosed with **acute coronary syndrome** within a maximum of 15 days prior to inclusion. Both **male** and **female** subjects are eligible to participate. All participants must have a confirmed diagnosis of **iron deficiency** at the time of hospital admission or within 15 days after the cardiac event, defined by serum **ferritin** levels below 100 ng/mL or **transferrin saturation** below 20%, according to established clinical guidelines. The iron deficiency must be untreated at the time of enrollment. Participants are required to have the cognitive ability to understand the study details and provide written **informed consent** prior to any trial-related procedures. The trial focuses on an elderly population with recent cardiovascular events and concurrent iron deficiency, representing a specific subgroup of patients with **cardiovascular disease**.

This is a Phase IV, open-label, randomized clinical trial evaluating the effect of intravenous iron administration on quality of life in elderly patients diagnosed with acute coronary syndrome and iron deficiency. The study investigates whether patients aged 65 years or older with confirmed iron deficiency following an acute coronary syndrome event experience improved quality of life when treated with intravenous ferric carboxymaltose compared to those who do not receive treatment. The trial is designed as a low interventional study utilizing an authorized medicinal product administered via intravenous administration at a maximum daily dose of 15 mg/kg and a maximum total dose of 1000 mg over a treatment period of 2 weeks.

The primary objective is to determine whether intravenous iron treatment results in better quality of life at 6 and 12 months of follow-up compared to patients who do not receive treatment. The primary endpoint is the change in EQ-5D-5L score at 6 and 12 months versus baseline in the intravenous iron group compared to the control group. Secondary endpoints include changes in FRAIL Scale score at 6 and 12 months versus baseline, changes in C-reactive protein and high-sensitivity C-reactive protein levels from baseline to 12 months, and the incidence of decompensated heart failure requiring hospitalization at 12 months. Additional secondary endpoints encompass the incidence of non-fatal myocardial infarction and stroke at 1 year, as well as all-cause mortality at 12 months. In a subgroup of participants, changes in iron metabolism markers including iron, ferritin, serum ferritin, soluble transferrin receptor, transferrin saturation, hypoxia-inducible factor-1, and hepcidin will be assessed from baseline to 12 months. Inflammatory markers such as C-reactive protein, high-sensitivity C-reactive protein, interleukin-1, interleukin-6, interleukin-10, interleukin-18, and tumor necrosis factor-alpha will also be evaluated in this subgroup. Further subgroup analyses include changes in biological age markers and telomere length from baseline to 12 months, as well as correlation of baseline Klotho and fibroblast growth factor 23 values with adverse clinical events at 12 months.

Eligible participants are patients aged 65 years or older with a confirmed diagnosis of acute coronary syndrome within a maximum of 15 days prior to inclusion. Iron deficiency must be confirmed at the time of hospital admission or within 15 days after the cardiac event, defined as serum ferritin less than 100 ng/mL or transferrin saturation less than 20 percent according to European Society of Cardiology guidelines and consensus recommendations. Participants must have the ability to understand the study details and provide written informed consent prior to any trial-related procedures. The trial is estimated to commence recruitment in January 2026 and is expected to conclude in January 2028, resulting in an overall trial duration of approximately 2 years.

Participant involvement in the study extends over a period of 12 months following randomization. The study includes a screening and inclusion visit during which eligibility criteria are verified, informed consent is obtained, and baseline assessments are performed including quality of life questionnaires, frailty scales, and laboratory evaluations of iron metabolism and inflammatory markers. Following randomization, participants in the intervention group receive intravenous ferric carboxymaltose treatment according to the dosing protocol, while the control group does not receive iron supplementation. Follow-up visits are conducted at 6 months and 12 months post-randomization to assess changes in quality of life scores, frailty measures, and clinical outcomes. At the 12-month visit, which serves as the end-of-study visit, final assessments are completed including repeat measurements of all primary and secondary endpoints. In the subgroup designated for additional biomarker analysis, blood samples are collected at baseline and at 12 months for evaluation of iron metabolism markers, inflammatory markers, biological age markers, and telomere length. Throughout the study period, adverse events including hospitalizations for heart failure decompensation, myocardial infarction, stroke, and mortality are recorded. Conditions that may lead to early termination from the study include withdrawal of consent by the participant, development of safety concerns requiring discontinuation of treatment, loss to follow-up, or death. The trial protocol specifies procedures for documentation and reporting of all early terminations to ensure comprehensive safety monitoring and data integrity.

The experimental medication utilized in this clinical trial is Ferinject, containing ferric carboxymaltose as the active substance. Ferinject is supplied as a 50 mg/ml dispersion for injection/infusion. The product is administered via intravenous administration. The dosing regimen consists of a maximum daily dose of 15 mg/kg body weight, with a maximum total dose not exceeding 1000 mg per administration. The maximum treatment period is specified as 2 weeks. Ferric carboxymaltose is classified under the ATC code B03AC as an iron trivalent, parenteral preparation, with the active substance being of polymer origin.

This Phase IV clinical trial is designed as an open-label, randomized study investigating the effect of intravenous iron supplementation on quality of life in elderly patients diagnosed with iron deficiency following acute coronary syndrome. The study population consists of patients aged 65 years or older. The trial compares outcomes between patients receiving intravenous iron treatment and those who do not receive such treatment, with quality of life assessments conducted at 6 and 12 months of follow-up.

Efficacy will be assessed using the EQ-5D-5L score as the primary endpoint, with measurements taken at baseline, 6 months, and 12 months. The primary analysis will compare the change in EQ-5D-5L score from baseline to 6 and 12 months between the intravenous iron treatment group and the control group. Secondary efficacy parameters include the change in FRAIL Scale score at 6 and 12 months compared to baseline. Additional secondary endpoints encompass changes in C-reactive protein and high-sensitivity C-reactive protein levels from baseline to 12 months, incidence of decompensated heart failure requiring hospitalization over 12 months, incidence of non-fatal myocardial infarction at 1 year, incidence of stroke at 1 year, and all-cause mortality at 12 months. In a subgroup of patients, changes in iron metabolism markers including iron, ferritin, serum ferritin, soluble transferrin receptor, transferrin saturation, hypoxia-inducible factor-1, and hepcidin will be measured from baseline to 12 months. Inflammatory markers such as C-reactive protein, high-sensitivity C-reactive protein, interleukin-1, interleukin-6, interleukin-10, interleukin-18, and tumor necrosis factor-alpha will also be assessed in this subgroup from baseline to 12 months. Changes in biological age markers and telomere length from baseline to 12 months will be evaluated in the subgroup. Correlation of baseline Klotho and fibroblast growth factor 23 values with adverse clinical events including heart failure decompensation, reinfarction, stroke, and all-cause mortality at 12 months will be analyzed in the subgroup.