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

Phase 4

Recruiting

• Conditions: Myocardial Infarction, Acute
• Interventions: Drug: Sodium Chloride 0.9% Inj; Drug: Ferinject

• Registration Number: NCT05759078
• Lead Sponsor: Wroclaw Medical University

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2022-09-22
• Study First Submitted: 2023-01-16
• Study First Submitted QC: 2023-02-24
• Study First Posted: 2023-03-08
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-19
• Last Update Posted: 2023-09-21
• Primary Completion: 2026-06-14
• Study Completion: 2026-06-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 2000

Inclusion Criteria

1. Age ≥18 years;

2. Diagnosis of AMI (STEMI or NSTEMI) up to 4 weeks before randomisation;

3. 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;

4. Presence of ≥3 factors (confirmed within up to 4 weeks before randomisation) (note: at least one of a-c must be present):

   1. LVEF ≤50%;
   2. NT-proBNP ≥400 pg/mL for subjects in sinus rhythm and NT-proBNP ≥800 pg/mL for subjects with atrial fibrillation;
   3. Clinical features of congestion/volume overload (including Killip class II or more) requiring i.v. loop diuretic use;
   4. Diagnosis of diabetes mellitus (also de novo diagnosis);
   5. Diagnosis of atrial fibrillation (any time in the past or de-novo diagnosis);
   6. Multivessel coronary disease (regardless of completeness of revascularisation during an index AMI);
   7. Not complete revascularisation or/and no reperfusion (during an index AMI);
   8. History of AMI (despite an index AMI);
   9. eGFR <60 mL/min/1.73m2;
   10. Age ≥70 years.

5. Written informed consent

Exclusion Criteria

1. Subject temperature>38 ͦ C or any infection requiring antibiotic therapy within 48 hours prior to randomisation;
2. Severe, symptomatic valve disorder;
3. Urgent hospitalisation for whatever reasons (percutaneous/surgical procedure requiring hospitalisation within 4 weeks prior to randomisation).
4. Body weight <50 kg;
5. Haemoglobin <8 g/dL or >15 g/dL;
6. Serum ferritin >400 ng/mL;
7. TSAT >40 %;
8. Active gastroenteral bleeding;
9. Known hypersensitivity to any of the administered preparations;
10. Treatment with erythropoiesis stimulating factors, i.v. iron therapy or blood transfusion within 6 months prior to randomisation;
11. 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;
12. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Sodium Chloride 0.9% Inj	70 mL of i.v. NaCl 0.9% infusion
Active	Ferinject	an i.v. 15-minute infusion of 20 mL Ferinject (containing 1000 mg of FCM) diluted in 50 mL of NaCl 0.9%

Primary Outcome Measures

Name	Time	Method
Time to CV death assessed during the 12-month follow-up	12 months	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): 1. Time to CV death assessed during the 12-month follow-up; 2. Number of HFE assessed during the 12-month follow-up; 3. Time to first HFE assessed during the 12-month follow-up; 4. 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).
Time to first HFE assessed during the 12-month follow-up	12 months	Time to first HFE
Number of HFE assessed during the 12-month follow-up	12 months	Number of HFE
Change in Quality of life measured using EQ-5D change from baseline to an assessment at 8-month visit	8 months	Change in Quality of life

Secondary Outcome Measures

Name	Time	Method
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);	12 months	First unplanned HF hospitalisation or unplanned visit at emergency
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);	12 months	All unplanned HF hospitalisations and unplanned visit at emergency
All unplanned HF hospitalisations 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);
CV death during the follow-up up to 12 months	12 months	CV death
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 and unplanned visit at emergency department due to HF during the follow-up up to 12 months (recurrent event model);

Trial Locations

Locations (35)

Ośrodek Kardiologii Inwazyjnej IKARDIA Sp. z o.o.; 🇵🇱 Nałęczów, Lubelskie, Poland

Zespół Opieki Zdrowotnej w Kłodzku; 🇵🇱 Kłodzko, Dolnośląskie, Poland

4Cardia Sp. z o.o.; 🇵🇱 Kraśnik, Lubelskie, Poland

Szpital Specjalistyczny im. J. Dietla w Krakowie; 🇵🇱 Kraków, Małopolskie, Poland

Centrum Kardiologii w Kluczborku Scanmed S.A.; 🇵🇱 Kluczbork, Opolskie, Poland

Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi; 🇵🇱 Łódź, Łódzkie, Poland

Wojskowy Instytut Medyczny - Państwowy Instytut Badawczy; 🇵🇱 Warsaw, Mazowieckie, Poland

Szpital Wojewódzki im. św. Łukasza SP ZOZ w Tarnowie; 🇵🇱 Tarnów, Małopolskie, Poland

Wojewódzki Szpital Specjalistyczny im. Janusza Korczaka w Słupsku Sp. z o.o.; 🇵🇱 Słupsk, Pomorskie, Poland

Uniwersyteckim Centrum Kliniczne w Gdańsku; 🇵🇱 Gdańsk, Pomorskie, Poland

Polsko-Amerykańskie Kliniki Serca, X Oddział Kardiologii Inwazyjnej, Elektrofizjologii i Elektrostymulacji w Tychach; 🇵🇱 Tychy, Śląskie, Poland

Uniwersytecki Szpital kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu; 🇵🇱 Wrocław, Dolnośląskie, Poland

4. Wojskowy Szpital Kliniczny z Polikliniką SP ZOZ; 🇵🇱 Wrocław, Dolnośląskie, Poland

Mazowiecki Szpital Bródnowski Sp. z o.o.; 🇵🇱 Warszawa, Mazowieckie, Poland

Szpital Specjalistyczny im. SS im. Henryka Klimontowicza w Gorlicach; 🇵🇱 Gorlice, Małopolskie, Poland

Centrum Opieki Medycznej w Jarosławiu; 🇵🇱 Jarosław, Podkarpackie, Poland

Dolnośląski Szpital Specjalistyczny im. T. Marciniaka - Centrum Medycyny Ratunkowej; 🇵🇱 Wrocław, Dolnośląskie, Poland

Centralny Szpital Kliniczny MSWiA w Warszawie; 🇵🇱 Warsaw, Mazowieckie, Poland

Podhalański Szpital Specjalistyczny im. Jana Pawła II w Nowym Targu; 🇵🇱 Nowy Targ, Małopolskie, Poland

Polsko-Amerykańskie Kliniki Serca Centrum Sercowo-Naczyniowe w Kędzierzynie Koźlu; 🇵🇱 Kędzierzyn-Koźle, Opolskie, Poland

Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu; 🇵🇱 Toruń, Kujawsko-pomorskie, Poland

Polsko-Amerykańskie Kliniki Serca Centrum Kardiologiczno-Angiologiczne w Sztumie; 🇵🇱 Sztum, Pomorskie, Poland

Samodzielny Publiczny Szpital Kliniczny nr 2 PUM w Szczecinie; 🇵🇱 Szczecin, Zachodniopomorskie, Poland

Wielospecjalistyczny Szpital SP ZOZ w Zgorzelcu; 🇵🇱 Zgorzelec, Dolnośląskie, Poland

Regionalny Szpital Specjalistyczny im. dr Wł. Biegańskiego w Grudziądzu; 🇵🇱 Grudziądz, Kujawsko-pomorskie, Poland

Uniwersytecki Szpital Kliniczny w Opolu; 🇵🇱 Opole, Opolskie, Poland

Polsko-Amerykańskie Kliniki Serca Centrum Kardiologii Med-Pro; 🇵🇱 Zgierz, Łódzkie, Poland

Vitamed Bydgoszcz; 🇵🇱 Bydgoszcz, Kujawsko-pomorskie, Poland

1. Wojskowy Szpital Kliniczny z Polikliniką Samodzielny Publiczny Zakład Opieki Zdrowotnej w Lublinie; 🇵🇱 Lublin, Lubelskie, Poland

Polsko-Amerykańskie Kliniki Serca Centrum Kardiologii i Kardiochirurgii w Bielsku-Białej; 🇵🇱 Bielsko-Biala, Śląskie, Poland

Szpital Uniwersytecki imienia Karola Marcinkowskiego w Zielonej Górze Sp. z o. o.; 🇵🇱 Zielona Góra, Lubuskie, Poland

Polsko-Amerykańskie Kliniki Serca Małopolskie Centrum Sercowo-Naczyniowe; 🇵🇱 Chrzanów, Małopolskie, Poland

Medicome Sp. z o.o.; 🇵🇱 Oświęcim, Małopolskie, Poland

Centrum Kardiologii Inwazyjnej Elektroterapii i Angiologii w Krośnie; 🇵🇱 Krosno, Podkarpackie, Poland

Nzoz Salusmed; 🇵🇱 Łódź, Łódzkie, Poland