Effect of intravenous ferric carboxymaltose on mortality and cardiovascular morbidity, and quality of life in iron deficient patients with recent myocardial infarction

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Wroclaw Medical University

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

21 Sep 2022 → ongoing

Decision date (initial)

2024-11-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Medical Research Agency

External identifiers

EU CT number

2024-517206-28-00

EudraCT number

2020-005740-27

ClinicalTrials.gov

NCT05759078

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Evaluation of the effect of i.v. FCM treatment compared with placebo on the risk of death, the risk of heart failure events (HFE*) (number of events and time to first event), NTproBNP concentration and the change in quality of life (QoL) assessed using EQ-5D during the follow-up up to 36-months 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).

Secondary objectives 4

1. Evaluation of the effect of i.v. FCM treatment compared with placebo on occurrence of composites of the primary outcome and other clinical outcomes (unplanned hospitalization for HF, 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], unplanned CV hospitalisations, all-cause, CV and non-CV deaths – separately and in combinations) in patients with recent AMI and ID during the follow-up up to 36-months
2. Evaluation of the effect of i.v. FCM treatment compared with placebo on change in quality of life (QoL) assessed using EQ-5D during the follow-up.
3. Evaluation of the NT-proBNP concentration during the follow-up.
4. Evaluation of safety and tolerance of i.v. FCM treatment as compared with placebo in patients with recent AMI and ID during the follow-up.

Conditions and MedDRA coding

Recent myocardial infarction associated with iron deficient

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥18 years.
2. Diagnosis of AMI (STEMI or NSTEMI) up to 4 weeks (28 days) before randomisation.
3. Presence of iron deficiency (ID) defined as transferrin saturation TSAT<20% assessed within up to 4 weeks (28 days) 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): a. LVEF ≤50%; b. NT-proBNP ≥400 pg/mL for subjects in sinus rhythm and NT-proBNP ≥800 pg/mL for subjects with atrial fibrillation; c. Clinical features of congestion/volume overload (including Killip class II or more) requiring i.v. loop diuretic use; d. Diagnosis of diabetes mellitus (also de novo diagnosis); e. Diagnosis of atrial fibrillation (any time in the past or de-novo diagnosis); f. Multivessel coronary disease (regardless of completeness of revascularisation during an index AMI); g. Not complete revascularisation or/and no reperfusion (during an index AMI); h. History of AMI (despite an index AMI); i. eGFR <60 mL/min/1.73m2; j. Age ≥70 years.
5. Written informed consent.

Exclusion criteria 14

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 >15,5 g/dL.
6. Serum ferritin >400 ng/mL.
7. Active gastroenteral bleeding.
8. Known hypersensitivity to any of the administered preparations.
9. Treatment with erythropoiesis stimulating factors, i.v. iron therapy or blood transfusion within 6 months prior to randomisation.
10. 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.
11. Documented liver diseases.
12. 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.
13. Pregnancy or lactation.
14. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. 1) Time to all-cause death assessed up to maximum 36-months follow-up;
2. 2) Number of HFE assessed up to maximum 36-months follow-up;
3. 3) Time to first HFE assessed up to maximum 36-months follow-up;
4. 4) Changes in serum NT-proBNP concentration from the start of the follow-up to the end of participation in the study assessed as the area under the curve;
5. 5) Changes in quality of life (QoL) measured using the EQ-5D questionnaire from the start of the follow-up to the end of participation in the study assessed as the area under the curve.

Secondary endpoints 5

1. First unplanned HF hospitalisation or unplanned visit at emergency department due to HF or CV death during the follow-up (time-to-event model).
2. All unplanned HF hospitalisations and unplanned visit at emergency department due to HF and CV death during the follow-up (recurrent event model).
3. All unplanned HF hospitalisations and unplanned visit at emergency department due to HF during the follow-up (recurrent event model).
4. All unplanned HF hospitalisations during the follow-up (recurrent event model).
5. CV death during thefollow-up.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Wroclaw Medical University

Sponsor organisation

Wroclaw Medical University

Address

Ul. Wybrzeze Ludwika Pasteura 1

City

Wroclaw

Postcode

50-367

Country

Poland

Scientific contact point

Organisation

Wroclaw Medical University

Contact name

University Clinical Research Support Center

Public contact point

Organisation

Wroclaw Medical University

Contact name

University Clinical Research Support Center

Locations

1 EU/EEA country · 32 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications