Evaluation of Intravenous Ferric Carboxymaltose on Mortality and Cardiovascular Morbidity in Iron-Deficient Patients Post-Myocardial Infarction
- Trial ID
- 2024-517206-28-00
- Protocol
- 2019/ABM/01/00081
- Sponsor
- Wroclaw Medical University
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effect of intravenous **ferric carboxymaltose** (FCM) treatment compared with placebo on the risk of death, the risk of heart failure events (HFE), NT-proBNP concentration, and the change in quality of life (QoL) assessed using EQ-5D during a follow-up period of up to 36 months in patients with recent myocardial infarction (AMI) and iron deficiency (ID). This is clinically relevant as it aims to determine whether FCM can improve survival rates, reduce heart failure-related complications, and enhance the quality of life in this patient population.
Secondary objectives include:
- Evaluation of the effect of i.v. FCM treatment compared with placebo on the occurrence of composites of the primary outcome and other clinical outcomes, such as unplanned hospitalization for heart failure, unplanned emergency department visits due to heart failure, significant intensification of diuretic therapy, unplanned cardiovascular hospitalizations, and all-cause, cardiovascular, and non-cardiovascular deaths, both separately and in combination, during the follow-up period.
- Assessment of the effect of i.v. FCM treatment compared with placebo on changes in quality of life (QoL) using the EQ-5D questionnaire during the follow-up.
- Evaluation of NT-proBNP concentration changes during the follow-up.
- Assessment of the safety and tolerance of i.v. FCM treatment compared with placebo in patients with recent AMI and ID during the follow-up.
Participants
The clinical trial involves participants diagnosed with a **recent myocardial infarction** associated with iron deficiency. The study population includes both male and female subjects aged 18 years and older. Participants are generally in a compromised health state due to their recent acute myocardial infarction (AMI) and associated conditions. The trial does not involve a vulnerable population. The sponsor has not provided the total number of participants. Selection criteria include a diagnosis of AMI (STEMI or NSTEMI) within four weeks prior to randomization and the presence of iron deficiency, defined by transferrin saturation (TSAT) of less than 20%. Participants must also exhibit at least three additional factors such as reduced left ventricular ejection fraction (LVEF ≤50%), elevated NT-proBNP levels, or clinical features of congestion requiring diuretic use. Lifestyle considerations such as diet and physical activity are not specified. Written informed consent is required for participation.
Plans and Procedures
The clinical trial is designed to evaluate the effect of **intravenous ferric carboxymaltose** on mortality, cardiovascular morbidity, and quality of life in patients with recent **myocardial infarction** and iron deficiency. This is a randomized, double-blind, placebo-controlled trial with an estimated duration of 36 months. Participants will be randomly assigned to receive either ferric carboxymaltose or a placebo, both administered via intravenous infusion. The trial aims to assess the time to all-cause death, the number of heart failure events, changes in serum NT-proBNP concentration, and quality of life using the EQ-5D questionnaire.
The study will include several visits, starting with a screening visit to confirm eligibility based on criteria such as age, recent diagnosis of myocardial infarction, and presence of iron deficiency. Participants must provide written informed consent. Follow-up visits will occur regularly to monitor the primary and secondary endpoints, including heart failure hospitalizations and cardiovascular death. The end-of-study visit will conclude the participant's involvement, assessing final outcomes and any adverse events.
Participant involvement is expected to last up to 36 months, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise safety. The trial will employ a hierarchical descending order win ratio approach to evaluate the main objectives, ensuring a comprehensive analysis of the treatment's impact on the specified endpoints.
Treatment
The clinical trial involves the administration of two treatments, each with distinct roles and characteristics. The **experimental medication** is **Ferinject**, a dispersion for injection/infusion containing **ferric carboxymaltose** as the active substance. This pharmaceutical form is designed for **intravenous infusion**. The maximum daily dose is 1000 mg, with a total dose not exceeding 1000 mg over the treatment period. The treatment duration is set for a maximum of 36 months. The administration of Ferinject is intended to evaluate its effect on mortality, cardiovascular morbidity, and quality of life in iron-deficient patients who have recently experienced a myocardial infarction. Compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.
The **non-experimental treatment** used in this study is a **placebo**, specifically a 0.9% **Sodium Chloride** solution for infusion. This solution is also administered via **intravenous infusion**. The maximum daily and total dose for the sodium chloride solution is 40 ml/kg, with the treatment period also extending up to 36 months. The placebo serves as a comparator to assess the efficacy and safety of the experimental treatment, Ferinject. The use of a placebo is critical in maintaining the study's integrity by providing a baseline for evaluating the experimental treatment's effects. Participant compliance with the placebo administration is similarly monitored to ensure the reliability of the trial results.
Efficacy
Efficacy in this clinical trial will be assessed through several primary and secondary endpoints. The primary endpoints include the time to all-cause death, the number of heart failure events (HFE), and the time to the first HFE, all evaluated over a follow-up period of up to 36 months. Additionally, changes in serum **NT-proBNP** concentration and quality of life (QoL) will be measured using the EQ-5D questionnaire, with both parameters assessed as the area under the curve from the start of the follow-up to the end of participation in the study.
Secondary endpoints will focus on cardiovascular outcomes, including the time to the first unplanned heart failure hospitalization or emergency department visit due to heart failure or cardiovascular death. Recurrent event models will be used to evaluate all unplanned heart failure hospitalizations and emergency department visits due to heart failure, as well as cardiovascular death during the follow-up period. These endpoints will provide a comprehensive assessment of the treatment's impact on mortality, morbidity, and patient-reported outcomes in individuals with recent myocardial infarction and iron deficiency.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥18 years.
- Diagnosis of AMI (STEMI or NSTEMI) up to 4 weeks (28 days) before randomisation.
- Presence of iron deficiency (ID) defined as transferrin saturation TSAT<20% assessed within up to 4 weeks (28 days) before randomisation.
- Presence of ≥3 factors (confirmed within up to 4 weeks before randomisation) (note: at least one of a-c must be present): a. LVEF ≤50%; b. NT-proBNP ≥400 pg/mL for subjects in sinus rhythm and NT-proBNP ≥800 pg/mL for subjects with atrial fibrillation; c. Clinical features of congestion/volume overload (including Killip class II or more) requiring i.v. loop diuretic use; d. Diagnosis of diabetes mellitus (also de novo diagnosis); e. Diagnosis of atrial fibrillation (any time in the past or de-novo diagnosis); f. Multivessel coronary disease (regardless of completeness of revascularisation during an index AMI); g. Not complete revascularisation or/and no reperfusion (during an index AMI); h. History of AMI (despite an index AMI); i. eGFR <60 mL/min/1.73m2; j. Age ≥70 years.
- Written informed consent.
Exclusion Criteria
- Subject temperature >38 ͦ C or any infection requiring antibiotic therapy within 48 hours prior to randomisation.
- Severe, symptomatic valve disorder.
- Urgent hospitalisation for whatever reasons (percutaneous/surgical procedure requiring hospitalisation within 4 weeks prior to randomisation).
- Body weight <50 kg.
- Haemoglobin <8 g/dL or >15,5 g/dL.
- Serum ferritin >400 ng/mL.
- Active gastroenteral bleeding.
- Known hypersensitivity to any of the administered preparations.
- Treatment with erythropoiesis stimulating factors, i.v. iron therapy or blood transfusion within 6 months prior to randomisation.
- Subject has known active malignancy of any organ system, i.e., clinical evidence of current malignancy or not in stable remission for at least 3 years since completion of last treatment with exception of non-invasive basal cell carcinoma, squamous cell carcinoma of the skin or cervical intra-epithelial neoplasia.
- Documented liver diseases.
- Participation in a device or drug trial within 3 months prior to randomisation or 5 half–lives, whichever period is longer, prior to the screening visit.
- Pregnancy or lactation.
- Any situation that may prevent the test from being performed in accordance with the protocol, or the consent of the investigator to be given in writing, including alcohol, drugs or any other substance overuse or addiction.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Poland | Recruiting | 01 Mar 2022 | 1000 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Ferinject 50 mg żelaza/ml dyspersja do wstrzykiwań/infuzji | Test | DYSPERSJA DO WSTRZYKIWAŃ/INFUZJI | INTRAVENOUS INFUSION | 1000 | 36 | PRD469674 |
0,9% Sodium Chloride–Braun, 9 mg/ml, roztwór do infuzji | Placebo | ROZTWÓR DO INFUZJI | INTRAVENOUS INFUSION | 40 | 36 | PRD563940 |