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

• Sponsor: Wroclaw Medical University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05759078
• Collaborator: (none)
• Enrollment: 2,000
• Locations: 15
• Arms: 2
• Anticipated Duration (Months): 44.7
• Patients Per Site: 133.3
• Patients Per Site Per Month: 3

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction, Acute	Drug: Ferinject; Drug: Sodium Chloride 0.9% Inj	Phase 4

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 2000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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].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].
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: A drip will be prepared by unblinded personnel using masked bottle, light brown lines for infusion, and administered immediately after preparation using a special curtain (screen).
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Sep 22, 2022
• Anticipated Primary Completion Date: Jun 14, 2026
• Anticipated Study Completion Date: Jun 14, 2026

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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): 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).

2. Number of HFE assessed during the 12-month follow-up [12 months]

   Number of HFE

3. Time to first HFE assessed during the 12-month follow-up [12 months]

   Time to first HFE

4. 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

1. 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

2. 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

3. 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);

4. 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);

5. CV death during the follow-up up to 12 months [12 months]

   CV death

Other Outcome Measures

1. First unplanned CV hospitalisation or CV death during the follow-up up to 12 months (time-to-event model); [12 months]

   First unplanned CV hospitalisation or CV death during the follow-up

2. All unplanned CV hospitalisations and CV death during the follow-up up to 12 months (recurrent event model); [12 months]

   All unplanned CV hospitalisations and CV death during the follow-up

3. All unplanned CV hospitalisations during the follow-up up to 12 months (recurrent event model); [12 months]

   All unplanned CV hospitalisations during the follow-up up to 12 months (recurrent event model);

4. Non-CV death during the follow-up up to 12 months [12 months]

   Non-CV death during the follow-up up to 12 months

5. All-cause death during the follow-up up to 12 months [12 months]

   All-cause death during the follow-up up to 12 months

6. Ambulatory significant intensification of diuretic therapy during the follow-up up to 12 months [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

7. Change in QoL scores (assessed using EQ-5D) from baseline to 4, 8 and 12 months since randomisation; [12 months]

   Change in QoL scores (assessed using EQ-5D) from baseline to 4, 8 and 12 months since randomisation;

8. Change in PGA 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

9. Change in NT-proBNP from baseline 4, 8 and 12 months since randomisation; [12 months]

   Change in NT-proBNP from baseline 4, 8 and 12 months since randomisation;

10. Change in other biomarkers from baseline to 4, 8 and 12 months since randomisation (substudy A) [12 months]

    Under redesigning process - details will be published at the later stage

11. Cost-effectiveness measures during the follow-up up to 12 months [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. Secondary and other aforementioned other outcomes during the followup up to 3 years (Substudy B - extension study). [up to 3 years]

    Substudy B - phone calls every 4 months up to 3 years of follow up (AE/SAE reports and enpoints).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age ≥18 years;

2. Diagnosis of AMI (STEMI or NSTEMI) within 14 days before randomisation;

3. Presence of iron deficiency (ID) defined as transferrin saturation TSAT<20% and/or serum ferritin <100 ng/mL assessed within up to 14 days before randomisation;

4. Presence of ≥3 factors (confirmed within up to 14 days before randomisation) (note: at least one of a-c must be present):

5. LVEF ≤50%;

6. NT-proBNP ≥400 pg/mL for subjects in sinus rhythm and NT-proBNP ≥800 pg/mL for subjects with atrial fibrillation;

7. Clinical features of congestion/volume overload (including Killip class II or more) requiring i.v. loop diuretic use;

8. Diagnosis of diabetes mellitus (also de novo diagnosis);

9. Diagnosis of atrial fibrillation (any time in the past or de-novo diagnosis);

10. Multivessel coronary disease (regardless of completeness of revascularisation during an index AMI);

11. Not complete revascularisation or/and no reperfusion (during an index AMI);

12. History of AMI (despite an index AMI);

13. eGFR <60 mL/min/1.73m2;

14. Age ≥70 years.

15. 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;

1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Uniwersytecki Szpital kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu	Wrocław	Dolnośląskie	Poland	50-556
2	4. Wojskowy Szpital Kliniczny z Polikliniką SP ZOZ	Wrocław	Dolnośląskie	Poland	50-981
3	Dolnośląski Szpital Specjalistyczny im. T. Marciniaka - Centrum Medycyny Ratunkowej	Wrocław	Dolnośląskie	Poland	54-049
4	Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie	Lublin	Lubelskie	Poland	20-954
5	Szpital Uniwersytecki imienia Karola Marcinkowskiego w Zielonej Górze Sp. z o. o.	Zielona Góra	Lubuskie	Poland	65-046
6	Wojskowy Instytut Medyczny - Państwowy Instytut Badawczy	Warsaw	Mazowieckie	Poland	04-349
7	Mazowiecki Szpital Bródnowski Sp. z o.o.	Warszawa	Mazowieckie	Poland	03-242
8	Polsko-Amerykańskie Kliniki Serca Małopolskie Centrum Sercowo-Naczyniowe	Chrzanów	Małopolskie	Poland	32-500
9	Medicome Sp. z o.o.	Oświęcim	Małopolskie	Poland	32-600
10	Szpital Wojewódzki im. św. Łukasza SP ZOZ w Tarnowie	Tarnów	Małopolskie	Poland	33-100
11	Centrum Kardiologii w Kluczborku Scanmed S.A.	Kluczbork	Opolskie	Poland	46-200
12	Centrum Opieki Medycznej w Jarosławiu	Jarosław	Podkarpackie	Poland	37-500
13	Wojewódzki Szpital Specjalistyczny im. Janusza Korczaka w Słupsku Sp. z o.o.	Słupsk	Pomorskie	Poland	76-200
14	Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi	Łódź	Łódzkie	Poland	92-213
15	Polsko-Amerykańskie Kliniki Serca, X Oddział Kardiologii Inwazyjnej, Elektrofizjologii i Elektrostymulacji w Tychach	Tychy	Śląskie	Poland	43-100

Sponsors and Collaborators

• Wroclaw Medical University

Investigators

• Principal Investigator: Piotr Ponikowski, Wroclaw Medical University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wroclaw Medical University
• ClinicalTrials.gov Identifier: NCT05759078
• Other Study ID Numbers: 2019/ABM/01/00081
• First Posted: Mar 8, 2023
• Last Update Posted: Mar 8, 2023
• Last Verified: Feb 1, 2023

• 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
• Keywords provided by Wroclaw Medical University: Myocardial infarction; acute; iron deficiency; Infusion; ferric carboxymaltose
• Additional relevant MeSH terms: Myocardial Infarction; Infarction

Study Results

No Results Posted as of Mar 8, 2023