Intravenous Iron Supplement for Iron Deficiency in Patients With Severe Aortic Stenosis

• Status: Active, not recruiting
• Trial end date: 2023-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Iron deficiency is a prevalent nutritional deficiency and a common cause of anemia. Although iron deficiency is traditionally linked to anemia, iron deficiency is prevalent even in the absence of anaemia and in itself limits function and survival. Iron deficiency is a common feature of various chronic diseases, and up to 50% of patients with heart failure have iron deficiency. Iron deficiency is more prevalent the more advanced the disease is and occurs more frequently in women. Iron deficiency comprises absolute iron deficiency (usually defined as ferritin < 100 ng/ml) as well as functional iron deficiency, in which iron supply is inadequate to meet the demand for the production of red blood cells and other cellular functions despite normal or abundant body iron stores. Iron deficiency is associated with poor exercise capacity, lethargy and reduced quality of life. Results from our studies have shown that iron deficiency is prevalent in patients with aortic stenosis. Some of the symptoms associated with aortic stenosis, such as fatigue, reduced exercise capacity, dyspnoea and cognitive dysfunction, have traditionally been thought to be caused by the haemodynamic derangements precipitated by the valvular stenosis. However, similar symptoms can be brought about by iron deficiency, and the investigators hypothesize that intravenous iron supplement will improve exercise capacity, muscle strength, cognition, health-related quality of life and myocardial function in patients with severe aortic stenosis and iron deficiency. This is a phase 2, double blind, randomised, placebo-controlled trial. Participants will be randomised in a 1:1 fashion to receive a single intravenous dose of iron isomaltoside (50 patients) or matching placebo (50 patients). The study is designed to show superiority with regard to the primary endpoint in patients assigned to active treatment versus patients allocated to the placebo arm. The main goal is to evaluate the effect of a single dose of intravenous iron isomaltoside on exercise capacity after transcatheter aortic valve implantation in patients with severe aortic stenosis and iron deficiency. For this study, the investigators have defined as serum ferritin < 100 µg/l or ferritin between 100 and 300 µg/l in combination with a transferrin saturation < 20 %.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Oslo University Hospital
• Treatments: Iron; Iron isomaltoside 1000

Criteria

Inclusion Criteria:

• Aortic stenosis patients with peak flow velocity (>3.5 m/s) scheduled for aortic valve replacement with TAVI

• Iron deficiency defined as serum ferritin < 100 µg/l or ferritin between 100 and 300 µg/l in combination with a transferrin saturation < 20 %.

• Age > 18 years.

• Signed informed consent and expected compliance with protocol.

Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following criteria:

• Anaemia (Haemoglobin < 100 mg/l)

• Haemochromatosis

• Haemosiderosis

• Porphyria cutanea tarda

• Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells

• Decompensated liver disease (Child-Pugh score 7 or higher)

• End-stage renal failure, i.e. eGFR < 15 ml/min or on renal replacement therapy

• Planned major surgery within 6 months

• On erythropoietin analogues

• Known sensitivity or intolerance to iron isomaltoside or other parenteral iron preparations

• Intravenous iron supplement within 6 months prior to inclusion

• A clear indication for intravenous iron supplement

• On oral iron substitution (unless the subject agrees to stop treatment prior to randomisation)

• Alcohol or drug abuse within 3 months of informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance with study procedures or study drug intake

• Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial or participating in another trial involving an investigational drug and/or follow-up

• Failure to obtain written informed consent

• Inability to walk at least 100 meters over 6 minutes

• Women of child-bearing potential (1)

1. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Menopause is defined as 12 months continuous amenorrhea without an alternative medical cause in a female ≥ 55 years old or 12 months of spontaneous and continuous amenorrhea with a follicle stimulating hormone (FSH) level > 40 IU/L (or according to the definition of "postmenopausal range" for the laboratory involved) in a female < 55 years old unless the subject has undergone bilateral oophorectomy.