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

Myocardial Infarction, Acute Clinical Trial

— INFERRCT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05759078
• Other study ID #: 2019/ABM/01/00081
• Status: Recruiting
• Phase: Phase 4
• Start date: September 22, 2022
• Est. completion date: June 14, 2026

Study information

• Verified date: September 2023
• Source: Wroclaw Medical University
• Contact: Marta Duda-Sikula
• Phone: 717840696
• Email: marta.duda-sikula[@]umw.edu.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: June 14, 2026
• Est. primary completion date: June 14, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• Myocardial Infarction, Acute

Intervention

Drug:
• Ferinject
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.
• Sodium Chloride 0.9% Inj
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.

Locations

Country	Name	City	State
Poland	Polsko-Amerykanskie Kliniki Serca Centrum Kardiologii i Kardiochirurgii w Bielsku-Bialej	Bielsko-Biala	Slaskie
Poland	Vitamed Bydgoszcz	Bydgoszcz	Kujawsko-pomorskie
Poland	Polsko-Amerykanskie Kliniki Serca Malopolskie Centrum Sercowo-Naczyniowe	Chrzanów	Malopolskie
Poland	Uniwersyteckim Centrum Kliniczne w Gdansku	Gdansk	Pomorskie
Poland	Szpital Specjalistyczny im. SS im. Henryka Klimontowicza w Gorlicach	Gorlice	Malopolskie
Poland	Regionalny Szpital Specjalistyczny im. dr Wl. Bieganskiego w Grudziadzu	Grudziadz	Kujawsko-pomorskie
Poland	Centrum Opieki Medycznej w Jaroslawiu	Jaroslaw	Podkarpackie
Poland	Polsko-Amerykanskie Kliniki Serca Centrum Sercowo-Naczyniowe w Kedzierzynie Kozlu	Kedzierzyn-Kozle	Opolskie
Poland	Zespól Opieki Zdrowotnej w Klodzku	Klodzko	Dolnoslaskie
Poland	Centrum Kardiologii w Kluczborku Scanmed S.A.	Kluczbork	Opolskie
Poland	Szpital Specjalistyczny im. J. Dietla w Krakowie	Kraków	Malopolskie
Poland	4Cardia Sp. z o.o.	Krasnik	Lubelskie
Poland	Centrum Kardiologii Inwazyjnej Elektroterapii i Angiologii w Krosnie	Krosno	Podkarpackie
Poland	Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi	Lódz	Lódzkie
Poland	Nzoz Salusmed	Lódz	Lódzkie
Poland	1. Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Lublinie	Lublin	Lubelskie
Poland	Osrodek Kardiologii Inwazyjnej IKARDIA Sp. z o.o.	Naleczów	Lubelskie
Poland	Podhalanski Szpital Specjalistyczny im. Jana Pawla II w Nowym Targu	Nowy Targ	Malopolskie
Poland	Uniwersytecki Szpital Kliniczny w Opolu	Opole	Opolskie
Poland	Medicome Sp. z o.o.	Oswiecim	Malopolskie
Poland	Wojewódzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.	Slupsk	Pomorskie
Poland	Samodzielny Publiczny Szpital Kliniczny nr 2 PUM w Szczecinie	Szczecin	Zachodniopomorskie
Poland	Polsko-Amerykanskie Kliniki Serca Centrum Kardiologiczno-Angiologiczne w Sztumie	Sztum	Pomorskie
Poland	Szpital Wojewódzki im. sw. Lukasza SP ZOZ w Tarnowie	Tarnów	Malopolskie
Poland	Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu	Torun	Kujawsko-pomorskie
Poland	Polsko-Amerykanskie Kliniki Serca, X Oddzial Kardiologii Inwazyjnej, Elektrofizjologii i Elektrostymulacji w Tychach	Tychy	Slaskie
Poland	Centralny Szpital Kliniczny MSWiA w Warszawie	Warsaw	Mazowieckie
Poland	Wojskowy Instytut Medyczny - Panstwowy Instytut Badawczy	Warsaw	Mazowieckie
Poland	Mazowiecki Szpital Bródnowski Sp. z o.o.	Warszawa	Mazowieckie
Poland	4. Wojskowy Szpital Kliniczny z Poliklinika SP ZOZ	Wroclaw	Dolnoslaskie
Poland	Dolnoslaski Szpital Specjalistyczny im. T. Marciniaka - Centrum Medycyny Ratunkowej	Wroclaw	Dolnoslaskie
Poland	Uniwersytecki Szpital kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw	Dolnoslaskie
Poland	Polsko-Amerykanskie Kliniki Serca Centrum Kardiologii Med-Pro	Zgierz	Lódzkie
Poland	Wielospecjalistyczny Szpital SP ZOZ w Zgorzelcu	Zgorzelec	Dolnoslaskie
Poland	Szpital Uniwersytecki imienia Karola Marcinkowskiego w Zielonej Górze Sp. z o. o.	Zielona Góra	Lubuskie

Sponsors (1)

Lead Sponsor	Collaborator
Wroclaw Medical University

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	First unplanned CV hospitalisation or CV death during the follow-up up to 12 months (time-to-event model);	First unplanned CV hospitalisation or CV death during the follow-up	12 months
Other	All unplanned CV hospitalisations and CV death during the follow-up up to 12 months (recurrent event model);	All unplanned CV hospitalisations and CV death during the follow-up	12 months
Other	All unplanned CV hospitalisations during the follow-up up to 12 months (recurrent event model);	All unplanned CV hospitalisations during the follow-up up to 12 months (recurrent event model);	12 months
Other	Non-CV death during the follow-up up to 12 months	Non-CV death during the follow-up up to 12 months	12 months
Other	All-cause death during the follow-up up to 12 months	All-cause death during the follow-up up to 12 months	12 months
Other	Ambulatory significant intensification of diuretic therapy during the follow-up up to 12 months	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) during the follow-up up to 12 months	12 months
Other	Change in QoL scores (assessed using EQ-5D) from baseline to 4, 8 and 12 months since randomisation;	Change in QoL scores (assessed using EQ-5D) from baseline to 4, 8 and 12 months since randomisation;	12 months
Other	Change in PGA from baseline to 4, 8 and 12 months since randomisation	Change in PGA from baseline to 4, 8 and 12 months since randomisation	12 months
Other	Change in NT-proBNP from baseline 4, 8 and 12 months since randomisation;	Change in NT-proBNP from baseline 4, 8 and 12 months since randomisation;	12 months
Other	Change in other biomarkers from baseline to 4, 8 and 12 months since randomisation (substudy A)	Under redesigning process - details will be published at the later stage	12 months
Other	Cost-effectiveness measures during the follow-up up to 12 months	Any unplanned CV hospitalisation (recurrent event model and time to event models) 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) during the follow-up up to 12 months; Change in QoL scores (assessed using EQ-5D) from baseline to 4, 8 and 12 months since randomisation; Change in PGA from baseline to 4, 8 and 12 months since randomisation	12 months
Other	Secondary and other aforementioned other outcomes during the followup up to 3 years (Substudy B - extension study).	Substudy B - phone calls every 4 months up to 3 years of follow up (AE/SAE reports and enpoints).	up to 3 years
Primary	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
Primary	Number of HFE assessed during the 12-month follow-up	Number of HFE	12 months
Primary	Time to first HFE assessed during the 12-month follow-up	Time to first HFE	12 months
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	CV death during the follow-up up to 12 months	CV death	12 months

External Links

•   INFERRCT study website