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

Official title

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

Overview

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: minimum of 8 months up to a maximum of 36 months. Primary Study Objective: Primary: Evaluation of the effect of i.v. FCM treatment compared with placebo on the risk of death, the risk of heart failure events (HFE\*) (number of events and time to first event), NTproBNP concentration and the change in quality of life (QoL) assessed using EQ-5D during the follow-up up to 36-months 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).

Interventions

• Drug Ferinject
  The first dose of either FCM will be administered during the first visit on the day of randomisation (V1). Then, the participants will be reassessed at 4, 8, 12, 18, 24 and 30 months (visits V2, V3, V4, V5, V6, V7). If safety criteria are not fulfilled, a patient in the active study arm will receive i.v. NaCl 0.9% during the particular visit.
• Drug Sodium Chloride 0.9% Inj
  The first dose of placebo will be administered during the first visit on the day of randomisation (V1). Then, the participants will be reassessed at 4, 8, 12, 18, 24 and 30 months (visits V2, V3, V4, V5, V6, V7).

Primary outcome measures

• Time to all-cause death assessed up to maximum 36-months follow-up; [Time frame: up to 36 months]
• Number of HFE assessed up to maximum 36-months follow-up [Time frame: up to 36 months]
• Time to first HFE assessed up to maximum 36-months follow-up [Time frame: up to 36 months]
• Changes in serum NT-proBNP concentration from the start of the follow-up to the end of participation in the study assessed as the area under the curve [Time frame: up to 36 months]
• Changes in quality of life (QoL) measured using the EQ-5D questionnaire from the start of the follow-up to the end of participation in the study assessed as the area under the curve [Time frame: up to 36 months]

Secondary outcome measures (5)

• First unplanned HF hospitalisation or unplanned visit at emergency department due to HF or CV death during the follow-up (time-to-event model) [Time frame: up to 36 months]
• All unplanned HF hospitalisations and unplanned visit at emergency department due to HF and CV death during the follow-up (recurrent event model); [Time frame: up to 36 months]
• All unplanned HF hospitalisations and unplanned visit at emergency department due to HF during the follow-up (recurrent event model) [Time frame: up to 36 months]
• All unplanned HF hospitalisations during the follow-up (recurrent event model); [Time frame: up to 36 months]
• CV death during the follow-up [Time frame: up to 36 months]

Eligibility 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):

• 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; 1. 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Poland · 43 centers

• Vitamed Bydgoszcz — Bydgoszcz
• Regionalny Szpital Specjalistyczny im. dr Wł. Biegańskiego w Grudziądzu — Grudziądz
• Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu — Torun
• Polsko-Amerykańskie Kliniki Serca Małopolskie Centrum Sercowo-Naczyniowe — Chrzanów
• Szpital Specjalistyczny im. SS im. Henryka Klimontowicza w Gorlicach — Gorlice
• Szpital Specjalistyczny im. J. Dietla w Krakowie — Krakow
• Podhalański Szpital Specjalistyczny im. Jana Pawła II w Nowym Targu — Nowy Targ
• Medicome Sp. z o.o. — Oświęcim
• … and 35 more centers

Identifiers

NCT: NCT05759078 · 2019/ABM/01/00081

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗