Effect of INtravenous FERRic Carboxymaltose Onmortality and Cardiovascular Morbidity, and Quality of Life in Iron Deficient Patients With Recent Myocardial infarCTion

Study Overview
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Brief Summary
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Non-commercial, multicentre, randomised, double-blind, parallel group, placebo-controlled clinical trial. Eligible patients were randomly assigned (1:1) using a secure, central, interactive, web-based response system, to intervention FCM or placebo arm. Time of observation 12 months [12 main study + 3 years follow up in substudy B]. Primary Study Objective: Primary: Evaluation of the effect of i.v. FCM treatment compared with placebo on the risk of cardiovascular (CV) death, the risk of heart failure events (HFE*) (number of events and time to first event) during the 12-month follow-up and the change in quality of life (QoL) assessed using EQ-5D during the 8-month follow-up in patients with recent AMI and ID (with an implementation of a win ratio approach in a hierarchical descending order). *HFE: unplanned hospitalization for HF (including unplanned visit at emergency department due to HF), ambulatory significant intensification of diuretic therapy (either starting i.v. loop diuretic or more than doubling oral loop diuretic dose or de novo initiation of oral loop diuretic therapy due to HF signs/symptoms).

Official Title
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Effect of INtravenous FERRic Carboxymaltose Onmortality and Cardiovascular Morbidity, and Quality of Life in Iron Deficient Patients With Recent Myocardial infarCTion SUBTITLE Prevention of Cardiovascular Death, Heart Failure Events and Deterioration in Quality of Life With INtravenous FERRic Carboxymaltose in Iron Deficient Patients With Recent Myocardial Infarction

Conditions
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Myocardial Infarction, Acute

Intervention / Treatment
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* Drug: Ferinject
* Drug: Sodium Chloride 0.9% Inj


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years; Diagnosis of AMI (STEMI or NSTEMI) up to 4 weeks before randomisation; Presence of iron deficiency (ID) defined as transferrin saturation TSAT<20% and/or serum ferritin <100 ng/mL assessed up to 4 weeks before randomisation; Presence of ≥3 factors (confirmed within up to 4 weeks before randomisation) (note: at least one of a-c must be present): LVEF ≤50%; NT-proBNP ≥400 pg/mL for subjects in sinus rhythm and NT-proBNP ≥800 pg/mL for subjects with atrial fibrillation; Clinical features of congestion/volume overload (including Killip class II or more) requiring i.v. loop diuretic use; Diagnosis of diabetes mellitus (also de novo diagnosis); Diagnosis of atrial fibrillation (any time in the past or de-novo diagnosis); Multivessel coronary disease (regardless of completeness of revascularisation during an index AMI); Not complete revascularisation or/and no reperfusion (during an index AMI); History of AMI (despite an index AMI); eGFR <60 mL/min/1.73m2; 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 g/dL; Serum ferritin >400 ng/mL; TSAT >40 %; 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; 14) Pregnancy or lactation; 15) 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Non-commercial, multicentre, randomised, double-blind, parallel group, placebo-controlled clinical trial. Eligible patients were randomly assigned (1:1) using a secure, central, interactive, web-based response system, to intervention FCM or placebo arm. Time of observation 12 months [12 main study + 3 years follow up in substudy B].
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>an i.v. 15-minute infusion of 20 mL Ferinject (containing 1000 mg of FCM) diluted in 50 mL of NaCl 0.9% | Drug: Ferinject<br>* The first dose of FCM will be administered during the first visit on the day of randomisation (V1). Then, the participants will be reassessed at 4 and 8 months (visits V2, V3) for: haemoglobin, serum ferritin and TSAT. They will receive an additional dose of 1000 mg of FCM during these visits if ferritin <100 ng/mL or/and TSAT <20% (ferritin cannot exceed 400 ng/dL, TSAT cannot exceed 40%, haemoglobin cannot exceed 15 g/dL). If these criteria are not fulfilled, a patient in the active study arm will receive i.v. NaCl 0.9% during the particular visit.<br>|
| Placebo Comparator: Placebo<br>70 mL of i.v. NaCl 0.9% infusion | Drug: Sodium Chloride 0.9% Inj<br>* The first dose of placebo will be administered during the first visit on the day of randomisation (V1). During visits V2 i V3 (at 4 and 8 months) they will receive next dose of placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to CV death assessed during the 12-month follow-up | Defined as: (with an implementation of a win ratio approach in a hierarchical descending order - pairwise comparison of each patient in the FCM group vs placebo group with the following hierarchy): Time to CV death assessed during the 12-month follow-up; Number of HFE assessed during the 12-month follow-up; Time to first HFE assessed during the 12-month follow-up; Change in QoL measured using EQ-5D change from baseline to an assessment at 8-month visit. *HFE: unplanned hospitalization for HF (including unplanned visit at emergency department due to HF), ambulatory significant intensification of diuretic therapy (either starting i.v. loop diuretic or more than doubling oral loop diuretic dose or de novo initiation of oral loop diuretic therapy due to HF signs/symptoms). | 12 months | 
| Number of HFE assessed during the 12-month follow-up | Number of HFE | 12 months | 
| Time to first HFE assessed during the 12-month follow-up | Time to first HFE | 12 months | 
| Change in Quality of life measured using EQ-5D change from baseline to an assessment at 8-month visit | Change in Quality of life | 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First unplanned HF hospitalisation or unplanned visit at emergency department due to HF or CV death during the follow-up up to 12 months (time-to-event model); | First unplanned HF hospitalisation or unplanned visit at emergency | 12 months | 
| All unplanned HF hospitalisations and unplanned visit at emergency department due to HF and CV death during the follow-up up to 12 months (recurrent event model); | All unplanned HF hospitalisations and unplanned visit at emergency | 12 months | 
| All unplanned HF hospitalisations and unplanned visit at emergency department due to HF during the follow-up up to 12 months (recurrent event model); | All unplanned HF hospitalisations and unplanned visit at emergency department due to HF during the follow-up up to 12 months (recurrent event model); | 12 months | 
| All unplanned HF hospitalisations during the follow-up up to 12 months (recurrent event model); | All unplanned HF hospitalisations during the follow-up up to 12 months (recurrent event model); | 12 months | 
| CV death during the follow-up up to 12 months | CV death | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myocardial infarction, acute, iron deficiency, Infusion, ferric carboxymaltose