Clinical trial NCT05759078: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Myocardial Infarction, Acute
Keywords: Myocardial infarction
acute
iron deficiency
Infusion
ferric carboxymaltose
Lead sponsor: Wroclaw Medical University
Sponsor class: OTHER
First posted: 2023-03-08
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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 \[12 main study + 3 years follow up in substudy B\].
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Time to CV death assessed during the 12-month follow-up
timeFrame: 12 months
measure: Number of HFE assessed during the 12-month follow-up
timeFrame: 12 months
measure: Time to first HFE assessed during the 12-month follow-up
timeFrame: 12 months
measure: Change in Quality of life measured using EQ-5D change from baseline to an assessment at 8-month visit
timeFrame: 8 months
Secondary outcomes:
measure: 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);
timeFrame: 12 months
measure: 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);
timeFrame: 12 months
measure: All unplanned HF hospitalisations and unplanned visit at emergency department due to HF during the follow-up up to 12 months (recurrent event model);
timeFrame: 12 months
measure: All unplanned HF hospitalisations during the follow-up up to 12 months (recurrent event model);
timeFrame: 12 months
measure: CV death during the follow-up up to 12 months
timeFrame: 12 months
Other outcomes:
measure: First unplanned CV hospitalisation or CV death during the follow-up up to 12 months (time-to-event model);
timeFrame: 12 months
measure: All unplanned CV hospitalisations and CV death during the follow-up up to 12 months (recurrent event model);
timeFrame: 12 months
measure: All unplanned CV hospitalisations during the follow-up up to 12 months (recurrent event model);
timeFrame: 12 months
measure: Non-CV death during the follow-up up to 12 months
timeFrame: 12 months
measure: All-cause death during the follow-up up to 12 months
timeFrame: 12 months
measure: Ambulatory significant intensification of diuretic therapy during the follow-up up to 12 months
timeFrame: 12 months
measure: Change in QoL scores (assessed using EQ-5D) from baseline to 4, 8 and 12 months since randomisation;
timeFrame: 12 months
measure: Change in PGA from baseline to 4, 8 and 12 months since randomisation
timeFrame: 12 months
measure: Change in NT-proBNP from baseline 4, 8 and 12 months since randomisation;
timeFrame: 12 months
measure: Change in other biomarkers from baseline to 4, 8 and 12 months since randomisation (substudy A)
timeFrame: 12 months
measure: Cost-effectiveness measures during the follow-up up to 12 months
timeFrame: 12 months
measure: Secondary and other aforementioned other outcomes during the followup up to 3 years (Substudy B - extension study).
timeFrame: up to 3 years
Locations:
city: Kłodzko
country: Poland
facility: Zespół Opieki Zdrowotnej w Kłodzku
state: Dolnośląskie
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
state: Dolnośląskie
city: Wrocław
country: Poland
facility: 4. Wojskowy Szpital Kliniczny z Polikliniką SP ZOZ
state: Dolnośląskie
city: Wrocław
country: Poland
facility: Dolnośląski Szpital Specjalistyczny im. T. Marciniaka - Centrum Medycyny Ratunkowej
state: Dolnośląskie
city: Zgorzelec
country: Poland
facility: Wielospecjalistyczny Szpital SP ZOZ w Zgorzelcu
state: Dolnośląskie
city: Bydgoszcz
country: Poland
facility: Vitamed Bydgoszcz
state: Kujawsko-pomorskie
city: Grudziądz
country: Poland
facility: Regionalny Szpital Specjalistyczny im. dr Wł. Biegańskiego w Grudziądzu
state: Kujawsko-pomorskie
city: Toruń
country: Poland
facility: Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu
state: Kujawsko-pomorskie
city: Kraśnik
country: Poland
facility: 4Cardia Sp. z o.o.
state: Lubelskie
city: Lublin
country: Poland
facility: 1. Wojskowy Szpital Kliniczny z Polikliniką Samodzielny Publiczny Zakład Opieki Zdrowotnej w Lublinie
state: Lubelskie
city: Nałęczów
country: Poland
facility: Ośrodek Kardiologii Inwazyjnej IKARDIA Sp. z o.o.
state: Lubelskie
city: Zielona Góra
country: Poland
facility: Szpital Uniwersytecki imienia Karola Marcinkowskiego w Zielonej Górze Sp. z o. o.
state: Lubuskie
city: Warsaw
country: Poland
facility: Centralny Szpital Kliniczny MSWiA w Warszawie
state: Mazowieckie
city: Warsaw
country: Poland
facility: Wojskowy Instytut Medyczny - Państwowy Instytut Badawczy
state: Mazowieckie
city: Warszawa
country: Poland
facility: Mazowiecki Szpital Bródnowski Sp. z o.o.
state: Mazowieckie
city: Chrzanów
country: Poland
facility: Polsko-Amerykańskie Kliniki Serca Małopolskie Centrum Sercowo-Naczyniowe
state: Małopolskie
city: Gorlice
country: Poland
facility: Szpital Specjalistyczny im. SS im. Henryka Klimontowicza w Gorlicach
state: Małopolskie
city: Kraków
country: Poland
facility: Szpital Specjalistyczny im. J. Dietla w Krakowie
state: Małopolskie
city: Nowy Targ
country: Poland
facility: Podhalański Szpital Specjalistyczny im. Jana Pawła II w Nowym Targu
state: Małopolskie
city: Oświęcim
country: Poland
facility: Medicome Sp. z o.o.
state: Małopolskie
city: Tarnów
country: Poland
facility: Szpital Wojewódzki im. św. Łukasza SP ZOZ w Tarnowie
state: Małopolskie
city: Kluczbork
country: Poland
facility: Centrum Kardiologii w Kluczborku Scanmed S.A.
state: Opolskie
city: Kędzierzyn-Koźle
country: Poland
facility: Polsko-Amerykańskie Kliniki Serca Centrum Sercowo-Naczyniowe w Kędzierzynie Koźlu
state: Opolskie
city: Opole
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Opolu
state: Opolskie
city: Jarosław
country: Poland
facility: Centrum Opieki Medycznej w Jarosławiu
state: Podkarpackie
city: Krosno
country: Poland
facility: Centrum Kardiologii Inwazyjnej Elektroterapii i Angiologii w Krośnie
state: Podkarpackie
city: Gdańsk
country: Poland
facility: Uniwersyteckim Centrum Kliniczne w Gdańsku
state: Pomorskie
city: Sztum
country: Poland
facility: Polsko-Amerykańskie Kliniki Serca Centrum Kardiologiczno-Angiologiczne w Sztumie
state: Pomorskie
city: Słupsk
country: Poland
facility: Wojewódzki Szpital Specjalistyczny im. Janusza Korczaka w Słupsku Sp. z o.o.
state: Pomorskie
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 2 PUM w Szczecinie
state: Zachodniopomorskie
city: Zgierz
country: Poland
facility: Polsko-Amerykańskie Kliniki Serca Centrum Kardiologii Med-Pro
state: Łódzkie
city: Łódź
country: Poland
facility: Nzoz Salusmed
state: Łódzkie
city: Łódź
country: Poland
facility: Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi
state: Łódzkie
city: Bielsko-Biala
country: Poland
facility: Polsko-Amerykańskie Kliniki Serca Centrum Kardiologii i Kardiochirurgii w Bielsku-Białej
state: Śląskie
city: Tychy
country: Poland
facility: Polsko-Amerykańskie Kliniki Serca, X Oddział Kardiologii Inwazyjnej, Elektrofizjologii i Elektrostymulacji w Tychach
state: Śląskie
Study officials:
affiliation: Wroclaw Medical University
name: Piotr Ponikowski
role: PRINCIPAL_INVESTIGATOR
References: