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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Myocardial Infarction, Acute
• Intervention / Treatment: Drug: Ferinject; Drug: Sodium Chloride 0.9% Inj

• Study Type: Interventional
• Enrollment (Estimated): 2000
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Marta Duda-Sikuła; Phone Number: 0048 717840696; Email: marta.duda-sikula@umw.edu.pl
• Study Contact Backup: Name: Julia Raińczuk; Phone Number: 717840697; Email: julia.rainczuk@umw.edu.pl

Study Locations

• Poland
  • Dolnośląskie
    • Kłodzko, Dolnośląskie, Poland, 57-300
      • Recruiting
      • Zespół Opieki Zdrowotnej w Kłodzku
      • Contact: Phone Number: 74 865 12 00
    • Wrocław, Dolnośląskie, Poland, 50-556
      • Recruiting
      • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
      • Contact: Phone Number: 71 736 42 76
    • Wrocław, Dolnośląskie, Poland, 50-981
      • Recruiting
      • 4. Wojskowy Szpital Kliniczny z Polikliniką SP ZOZ
      • Contact: Phone Number: 26 166 05 55
    • Wrocław, Dolnośląskie, Poland, 54-049
      • Recruiting
      • Dolnośląski Szpital Specjalistyczny im. T. Marciniaka - Centrum Medycyny Ratunkowej
      • Contact: Phone Number: 71 306 44 19
    • Zgorzelec, Dolnośląskie, Poland, 59-900
      • Recruiting
      • Wielospecjalistyczny Szpital SP ZOZ w Zgorzelcu
      • Contact: Phone Number: 75 772 29 00
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-079
      • Recruiting
      • Vitamed Bydgoszcz
      • Contact: Phone Number: 52 347 88 15
    • Grudziądz, Kujawsko-pomorskie, Poland, 86-300
      • Recruiting
      • Regionalny Szpital Specjalistyczny im. dr Wł. Biegańskiego w Grudziądzu
      • Contact: Phone Number: 56 641 44 44
    • Toruń, Kujawsko-pomorskie, Poland, 87-100
      • Recruiting
      • Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu
      • Contact: Phone Number: 56 679 31 00
  • Lubelskie
    • Kraśnik, Lubelskie, Poland, 23-204
      • Recruiting
      • 4Cardia Sp. z o.o.
      • Contact: Phone Number: 81 458 77 88
    • Lublin, Lubelskie, Poland, 20-049
      • Active, not recruiting
      • 1. Wojskowy Szpital Kliniczny z Polikliniką Samodzielny Publiczny Zakład Opieki Zdrowotnej w Lublinie
    • Nałęczów, Lubelskie, Poland, 24-140
      • Active, not recruiting
      • Ośrodek Kardiologii Inwazyjnej IKARDIA Sp. z o.o.
  • Lubuskie
    • Zielona Góra, Lubuskie, Poland, 65-046
      • Recruiting
      • Szpital Uniwersytecki imienia Karola Marcinkowskiego w Zielonej Górze Sp. z o. o.
      • Contact: Phone Number: 68 329 62 00
  • Mazowieckie
    • Warsaw, Mazowieckie, Poland, 04-349
      • Recruiting
      • Wojskowy Instytut Medyczny - Panstwowy Instytut Badawczy
      • Contact: Phone Number: 26 181 76 66
    • Warsaw, Mazowieckie, Poland, 02-507
      • Active, not recruiting
      • Centralny Szpital Kliniczny MSWiA w Warszawie
    • Warszawa, Mazowieckie, Poland, 03-242
      • Recruiting
      • Mazowiecki Szpital Bródnowski Sp. z o.o.
      • Contact: Phone Number: 22 326 52 26
  • Małopolskie
    • Chrzanów, Małopolskie, Poland, 32-500
      • Recruiting
      • Polsko-Amerykańskie Kliniki Serca Małopolskie Centrum Sercowo-Naczyniowe
      • Contact: Phone Number: 32 758 69 00
    • Gorlice, Małopolskie, Poland, 38-300
      • Active, not recruiting
      • Szpital Specjalistyczny im. SS im. Henryka Klimontowicza w Gorlicach
    • Kraków, Małopolskie, Poland, 31-121
      • Recruiting
      • Szpital Specjalistyczny im. J. Dietla w Krakowie
      • Contact: Phone Number: 12 68 76 200
    • Nowy Targ, Małopolskie, Poland, 34-400
      • Recruiting
      • Podhalański Szpital Specjalistyczny im. Jana Pawła II w Nowym Targu
      • Contact: Phone Number: 18 263 30 00
    • Oświęcim, Małopolskie, Poland, 32-600
      • Recruiting
      • Medicome Sp. z o.o.
      • Contact: Phone Number: 48 505 121 703
    • Tarnów, Małopolskie, Poland, 33-100
      • Recruiting
      • Szpital Wojewódzki im. św. Łukasza SP ZOZ w Tarnowie
      • Contact: Phone Number: 14 631 50 00
  • Opolskie
    • Kluczbork, Opolskie, Poland, 46-200
      • Recruiting
      • Centrum Kardiologii w Kluczborku Scanmed S.A.
      • Contact: Phone Number: 77 410 82 18
    • Kędzierzyn-Koźle, Opolskie, Poland, 47-200
      • Not yet recruiting
      • Polsko-Amerykańskie Kliniki Serca Centrum Sercowo-Naczyniowe w Kędzierzynie Koźlu
      • Contact: Phone Number: 77 472 25 65
    • Opole, Opolskie, Poland, 45-401
      • Recruiting
      • Uniwersytecki Szpital Kliniczny w Opolu
      • Contact: Phone Number: 77 452 07 45
  • Podkarpackie
    • Jarosław, Podkarpackie, Poland, 37-500
      • Recruiting
      • Centrum Opieki Medycznej w Jarosławiu
      • Contact: Phone Number: 16 621 54 21
    • Krosno, Podkarpackie, Poland, 38-400
      • Active, not recruiting
      • Centrum Kardiologii Inwazyjnej Elektroterapii i Angiologii w Krośnie
  • Pomorskie
    • Gdańsk, Pomorskie, Poland, 80-952
      • Not yet recruiting
      • Uniwersyteckim Centrum Kliniczne w Gdańsku
      • Contact: Phone Number: 58 349 20 00
    • Sztum, Pomorskie, Poland, 82-400
      • Not yet recruiting
      • Polsko-Amerykańskie Kliniki Serca Centrum Kardiologiczno-Angiologiczne w Sztumie
      • Contact: Phone Number: 55 625 92 20
    • Słupsk, Pomorskie, Poland, 76-200
      • Recruiting
      • Wojewódzki Szpital Specjalistyczny im. Janusza Korczaka w Słupsku Sp. z o.o.
      • Contact: Phone Number: 59 846 07 00
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland, 70-111
      • Active, not recruiting
      • Samodzielny Publiczny Szpital Kliniczny Nr 2 Pum W Szczecinie
  • Łódzkie
    • Zgierz, Łódzkie, Poland, 95-100
      • Not yet recruiting
      • Polsko-Amerykańskie Kliniki Serca Centrum Kardiologii Med-Pro
      • Contact: Phone Number: 42 231 47 00
    • Łódź, Łódzkie, Poland, 91-002
      • Active, not recruiting
      • Nzoz Salusmed
    • Łódź, Łódzkie, Poland, 92-213
      • Recruiting
      • Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi
      • Contact: Phone Number: 42 201 42 40
  • Śląskie
    • Bielsko-Biala, Śląskie, Poland, 43-316
      • Not yet recruiting
      • Polsko-Amerykańskie Kliniki Serca Centrum Kardiologii i Kardiochirurgii w Bielsku-Białej
      • Contact: Phone Number: 33 828 93 70
    • Tychy, Śląskie, Poland, 43-100
      • Recruiting
      • Polsko-Amerykańskie Kliniki Serca, X Oddział Kardiologii Inwazyjnej, Elektrofizjologii i Elektrostymulacji w Tychach
      • Contact: Phone Number: 32 758 67 00

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; 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; 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.
Placebo Comparator: Placebo; 70 mL of i.v. NaCl 0.9% infusion	Drug: 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Non-CV death during the follow-up up to 12 months	Non-CV death during the follow-up up to 12 months	12 months
All-cause death during the follow-up up to 12 months	All-cause death during the follow-up up to 12 months	12 months
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Wroclaw Medical University
• Investigators: Principal Investigator: Piotr Ponikowski, Wroclaw Medical University

Publications and helpful links

Helpful Links

• INFERRCT study website

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2022
• Primary Completion (Estimated): June 14, 2026
• Study Completion (Estimated): June 14, 2026

Study Registration Dates

• First Submitted: January 16, 2023
• First Submitted That Met QC Criteria: February 24, 2023
• First Posted (Actual): March 8, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: acute; Myocardial infarction; ferric carboxymaltose; iron deficiency; Infusion
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction
• Other Study ID Numbers: 2019/ABM/01/00081

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No