Effect of Intravenous Iron on Quality of Life in Older Patients With Acute Coronary Syndrome (HI-COR-65)

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 goal of this phase IV, open-label, randomized clinical trial is to evaluate whether intravenous iron improves quality of life in adults aged 65 years and older with iron deficiency after an acute coronary syndrome (ACS).

The main questions it aims to answer are:

• Does intravenous iron improve quality of life at 6 and 12 months?
• Does it reduce frailty and adverse clinical outcomes?

Researchers will compare intravenous ferric carboxymaltose with standard of care.

Participants will:

• Be randomly assigned to receive intravenous iron or standard care
• Attend three study visits over 12 months
• Complete questionnaires and undergo blood tests

Study Overview

• Status: Recruiting
• Conditions: Elderly (People Aged 65 or More); Acute Coronary Syndromes (ACS); Iron Deficiencies
• Intervention / Treatment: Drug: Ferric Carboxymaltose Injection [Ferinject]

Detailed Description

Acute coronary syndrome (ACS) remains one of the leading causes of morbidity and mortality in adults aged 65 years and older. Iron deficiency is a frequent condition in this population following an ACS event and has been associated with impaired functional capacity, increased frailty, worse quality of life, and poorer clinical outcomes. While intravenous iron supplementation has demonstrated clinical benefits in patients with heart failure, its role in older patients with iron deficiency after ACS has not been systematically evaluated.

This phase IV, multicenter, open-label, randomized clinical trial has been designed to assess the impact of intravenous iron administration on quality of life and clinical outcomes in older patients with iron deficiency following ACS. The study will include patients aged 65 years or older diagnosed with ACS within the previous 15 days and presenting with iron deficiency according to current European Society of Cardiology criteria.

Eligible participants will be randomized in a 1:1 ratio to receive either a single intravenous dose of ferric carboxymaltose, administered according to body weight and baseline hemoglobin levels, or standard of care without intravenous iron supplementation. Randomization will be centralized and stratified by participating center. Given the nature of the intervention, the study will be conducted in an open-label fashion.

Participants will be followed for 12 months after randomization, with study visits scheduled at baseline, 6 months, and 12 months. Throughout follow-up, comprehensive clinical assessments will be performed, including evaluation of quality of life using the EQ-5D-5L questionnaire and assessment of frailty using the FRAIL scale. Clinical events such as heart failure decompensation, recurrent myocardial infarction, stroke, and all-cause mortality will be systematically recorded.

In addition, serial blood samples will be collected to analyze iron metabolism parameters and inflammatory biomarkers. Exploratory analyses will focus on the assessment of biological aging and cardiovascular risk markers, including DNA methylation of the ELOVL2 gene, telomere length, and circulating levels of Klotho and fibroblast growth factor 23 (FGF23). These analyses aim to provide mechanistic insights into the potential effects of iron repletion on biological aging and cardiovascular risk in this vulnerable population.

The overall duration of the study is two years, including a one-year recruitment period and a one-year follow-up period. The trial is sponsored by INCLIVA - Health Research Institute and conducted across multiple centers in Spain. The results of this study are expected to provide robust clinical evidence to support optimized management of iron deficiency in older patients following ACS, with the potential to inform future clinical guidelines and improve patient-centered outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 538
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Clara Bonanad Lozano, Doctor; Phone Number: +34 686 10 70 71; Email: clarabonanad@gmail.com
• Study Contact Backup: Name: Claudio Rivadulla Varela, Doctor; Phone Number: +34 625 11 46 86; Email: c.rivare@hotmail.com

Study Locations

• Spain
  • Badajoz, Spain, 06080
    • Recruiting
    • Hospital Universitario de Badajoz
    • Contact: Javier Pérez Cervera, Doctor; Phone Number: +34637998882; Email: jperezcervera@gmail.com
    • Principal Investigator: Javier Pérez Cervera, Doctor
  • Barcelona, Spain, 08036
    • Not yet recruiting
    • Hospital Clinic De Barcelona
    • Contact: Pedro Luis Cepas Guillén, Doctor; Phone Number: +34662038836; Email: CEPAS@clinic.cat
    • Principal Investigator: Pedro Luis Cepas Guillén, Doctor
  • Granada, Spain, 18016
    • Recruiting
    • Hospital Universitario Clínico San Cecilio
    • Contact: Diego Segura-Rodríguez, Doctor; Phone Number: +34958023000; Email: diegoseguracardio@gmail.com
    • Principal Investigator: Diego Segura-Rodríguez, Doctor
  • León, Spain, 24071
    • Not yet recruiting
    • Hospital Universitario de Leon
    • Contact: Maria Thiscal López Lluva, Doctor; Phone Number: +34 652 684 953; Email: mtl.lluva@gmail.com
    • Principal Investigator: Maria Thiscal López Lluva, Doctor
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clinico San Carlos
    • Contact: David Vivas Balcones, Doctor; Phone Number: +34658477955; Email: dvivas@secardiologia.es
  • Pamplona, Spain, 31008
    • Not yet recruiting
    • Hospital Universitario de Navarra
    • Contact: Gonzalo Luis Alonso Salinas, Doctor; Email: gonzalol.alonso@gmail.com
    • Principal Investigator: Gonzalo Luis Alonso Salinas, Doctor
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clinico Universitario de Valencia
    • Contact: Clara Bonanad Lozano, Doctor; Phone Number: +34 686 10 70 71; Email: clarabonanad@gmail.com
    • Principal Investigator: Clara Bonanad Lozano, Doctor
    • Sub-Investigator: Claudio Rivadulla Varela, Doctor
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Recruiting
      • Hospital Clínico Universitario Virgen de la Arrixaca
      • Contact: María Asunción Esteve Pastor, Doctor; Phone Number: +34968381027; Email: masunep@gmail.com
      • Principal Investigator: María Asunción Esteve Pastor, Doctor
  • Pontevedra
    • Vigo, Pontevedra, Spain
      • Not yet recruiting
      • Hospital Álvaro Cunqueiro
      • Contact: Sergio Raposeiras Roubin, Doctor; Phone Number: +34886209106; Email: raposeiras26@hotmail.com
      • Principal Investigator: Sergio Raposeiras Roubin, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 65 years.
2. Hospitalization for confirmed acute coronary syndrome (ACS) within 15 days prior to enrollment.

3. Iron deficiency diagnosed at admission or within 15 days after the index ACS event, defined as:

   • Serum ferritin < 100 ng/mL, OR
   • Transferrin saturation (TSAT) < 20%.
4. Ability to provide written informed consent prior to participation.

Exclusion Criteria:

1. Active malignancy.
2. End-stage or terminal illness as determined by the IDC-Pal score.
3. Known heart failure with left ventricular ejection fraction (LVEF) < 40% prior to enrollment, or development of LVEF < 40% during hospitalization or within 15 days after ACS.
4. Chronic dialysis or advanced renal or hepatic failure.
5. Severe anemia (hemoglobin < 10 g/dL) at the time of ACS or within 15 days after the event.
6. Prior treatment with intravenous or oral iron within 12 months before the index ACS.
7. Known hypersensitivity to ferric carboxymaltose, other parenteral iron products, or any component of the formulation.
8. Evidence of iron overload or disorders of iron metabolism.
9. Ongoing bacteremia or active systemic infection.
10. Participation in another interventional clinical trial involving an investigational medicinal product.
11. Any condition that, in the investigator's opinion, would compromise safety, protocol compliance, or study integrity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention arm; Intravenous iron administered according to protocol and SmPC.	Drug: Ferric Carboxymaltose Injection [Ferinject]; Intervention Description (Treatment Arm) Single intravenous administration of ferric carboxymaltose (Ferinject®) given at baseline within 15 days after the index acute coronary syndrome. The total iron dose is individually calculated according to body weight and hemoglobin levels, in accordance with the approved Summary of Product Characteristics (maximum 15 mg/kg, not exceeding 2,000 mg). The drug is administered in a monitored hospital setting. No additional iron doses are planned during follow-up. Intervention Description (Control Arm) Standard post-acute coronary syndrome care without specific treatment for iron deficiency. No intravenous or oral iron supplementation is administered per protocol.
No Intervention: Control arm; No specific intervention for iron deficiency (standard of care post-acute coronary syndrome)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in health-related quality of life measured using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) index score	Change from baseline in health-related quality of life assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L). The EQ-5D-5L index score ranges from 0 to 1, where 0 represents the worst health state and 1 represents full health. Higher scores indicate better health-related quality of life. Scores will be evaluated at 6 and 12 months and compared with baseline between participants receiving intravenous ferric carboxymaltose and those receiving no iron treatment.	Baseline, Month 6 and Month 12.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in frailty status assessed using the Fatigue, Resistance, Ambulation, Illnesses, and Loss of Weight (FRAIL) scale	Change from baseline in frailty status assessed using the Fatigue, Resistance, Ambulation, Illnesses, and Loss of Weight (FRAIL) scale. The FRAIL scale classifies participants as robust, pre-frail, or frail based on questionnaire responses.	Baseline, Month 6 and Month 12.
Incidence of heart failure hospitalization	Occurrence of hospitalizations due to decompensated heart failure during follow-up.	Up to 12 months
Incidence of recurrent myocardial infarction	Occurrence of non-fatal myocardial infarction during follow-up.	Up to 12 months
Incidence of stroke	Occurrence of ischemic or hemorrhagic stroke during follow-up.	Up to 12 months
All-cause mortality	Death from any cause during the 12-month follow-up period.	Up to 12 months
Change in C-reactive protein levels (inflammatory marker)	Change from baseline in C-reactive protein (CRP) levels. Units: mg/dl	Baseline and 12 months follow-up
Change in high-sensitivity C-reactive protein levels (inflammatory marker)	Change from baseline in high-sensitivity C-reactive protein (CRP) levels. Units: mg/L	Baseline and 12 months follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in serum ferritin concentration	Change from baseline in serum ferritin concentration measured in blood samples in a predefined subgroup of participants. Units: ng/mL	Baseline and 12 months
Change from baseline in transferrin saturation	Change from baseline in transferrin saturation (TSAT) measured in blood samples in a predefined subgroup of participants. Transferrin saturation will be reported as percentage (%).	Baseline and 12 months
Change from baseline in soluble transferrin receptor concentration	Change from baseline in soluble transferrin receptor (sTfR) concentration measured in blood samples in a predefined subgroup of participants. Concentrations will be reported in milligrams per liter (mg/L).	Baseline and 12 months
Change from baseline in serum hepcidin concentration	Change from baseline in serum hepcidin concentration measured in blood samples in a predefined subgroup of participants. Concentrations will be reported in nanograms per milliliter (ng/mL).	Baseline and 12 months
Change from baseline in hypoxia-inducible factor 1 (HIF-1) levels	Change from baseline in hypoxia-inducible factor 1 (HIF-1) levels measured in blood samples in a predefined subgroup of participants. Values will be reported in ng/ul.	Baseline and 12 months
Change from baseline in interleukin-1 concentration	Change from baseline in interleukin-1 (IL-1) concentration measured in blood samples in a predefined subgroup of participants. Values will be reported in nanograms per microliter (ng/µL).	Baseline and at 12 months follow-up
Change from baseline in interleukin-6 concentration	Change from baseline in interleukin-6 (IL-6) concentration measured in blood samples in a predefined subgroup of participants. Values will be reported in nanograms per microliter (ng/µL).	Baseline and at 12 months follow-up
Change from baseline in interleukin-10 concentration	Change from baseline in interleukin-10 (IL-10) concentration measured in blood samples in a predefined subgroup of participants. Values will be reported in nanograms per microliter (ng/µL).	Baseline and at 12 months follow-up
Change from baseline in interleukin-18 concentration	Change from baseline in interleukin-18 (IL-18) concentration measured in blood samples in a predefined subgroup of participants. Values will be reported in nanograms per microliter (ng/µL).	Baseline and at 12 months follow-up
Change from baseline in tumor necrosis factor alpha concentration	Change from baseline in tumor necrosis factor alpha (TNF-α) concentration measured in blood samples in a predefined subgroup of participants. Values will be reported in nanograms per microliter (ng/µL).	Baseline and at 12 months follow-up
Change from baseline in epigenetic age acceleration measured by ELOVL2 DNA methylation	Change from baseline in epigenetic age acceleration assessed using DNA methylation of the ELOVL2 gene in blood samples from a predefined subgroup of participants. Epigenetic age acceleration will be reported in years of biological age.	Baseline and at 12 months follow-up
Change from baseline in telomere length	Change from baseline in telomere length measured using the telomere-to-single copy gene (T/S) ratio in blood samples from a predefined subgroup of participants.	Baseline and at 12 months follow-up
Association between baseline Klotho concentration and occurrence of major adverse cardiovascular events.	Association between baseline Klotho concentration measured in blood samples and the occurrence of major adverse cardiovascular events (MACE) during follow-up in a predefined subgroup of participants. Klotho concentrations will be reported in nanograms per microliter (ng/µL).	Baseline and through Month 12 follow-up.
Association between baseline fibroblast growth factor 23 concentration and occurrence of major adverse cardiovascular events.	Association between baseline fibroblast growth factor 23 (FGF23) concentration measured in blood samples and the occurrence of major adverse cardiovascular events (MACE) during follow-up in a predefined subgroup of participants. Concentrations will be reported in nanograms per microliter (ng/µL).	Baseline and through Month 12 follow-up.

Collaborators and Investigators

• Sponsor: Fundación para la Investigación del Hospital Clínico de Valencia
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: March 2, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Quality of life; Acute coronary syndrome; Myocardial infarction; Older adults; Frailty; Telomere length; Iron deficiency; FGF23; Intravenous iron; Ferric carboxymaltose; Klotho; Cardiovascular outcomes; Biological aging; ELOVL2 methylation
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Metabolic Diseases; Infarction; Necrosis; Myocardial Ischemia; Ischemia; Iron Metabolism Disorders; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Frailty; Iron Deficiencies; Myocardial Infarction; Acute Coronary Syndrome; ferric carboxymaltose
• Other Study ID Numbers: HI-COR-65

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No