Intravenous Iron Supplement for Iron Deficiency in Cardiac Transplant Recipients (IronIC)

University of Oslo (UIO)

Status and phase: Completed; Phase 3; Phase 2

Conditions: Heart Transplant Recipients

Treatments: Drug: Iron Isomaltoside 1000; Other: Placebo: NaCl 0,9%

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03662789

IronIC

Details and patient eligibility

About

Iron deficiency is prevalent in heart transplant recipients, and may be associated with reduced functional capacity. The IronIC trial is designed to assess the effect of intravenous iron isomaltoside on exercise capacity, muscle strength, cognition and quality of life in iron-deficient heart transplant recipients

Full description

Iron deficiency is prevalent in patients with heart failure. Iron deficiency is associated with a worse prognosis, and randomised controlled trials have shown that correction of iron deficiency with intravenous iron therapy improves functional capacity, quality of life, and 6-minute walk distance. Current guidelines therefore recommend intravenous iron substitution in patients with heart failure with reduced ejection fraction and iron deficiency. Intravenous iron is more effective, better tolerated, and improves quality of life to a greater extent than oral iron supplements. In the IRONOUT HF trial, in which 225 patients with systolic heart failure were randomised to oral iron supplement or placebo, there was no effect on oxygen uptake, 6-minute walk distance, or quality of life. The authors attributed the negative results to the minimal effect on iron stores, suggesting that oral iron does not adequately replenish iron stores in patients with heart failure.

Cardiac allograft recipients resemble patients with heart failure in many respects. Prior to transplantation, and in some instances after heart transplantation, they have had overt heart failure. Moreover, due to the immunologic challenge posed by the allograft, and their susceptibility to infection due to immunosuppressive treatment, cardiac allograft recipients have low-grade inflammation. This low-grade inflammation makes it difficult to interpret iron stores, and results in dysregulated iron metabolism.

There have been no studies to assess the effect of intravenous iron therapy in heart transplant recipients who have iron deficiency. There is reason to believe that a liberal definition of iron deficiency should be used in cardiac allograft recipients, and the investigators have elected to use the well-established definition used in patients with heart failure: serum ferritin < 100 µg/l or ferritin between 100 and 300 µg/l in combination with a transferrin saturation < 20 %. Because oral iron supplement is less effective then intravenous iron in general, and in patients with heart failure in particular, the investigators assume that oral iron supplement is inadequate in heart transplant recipients. the investigators have designed the IronIC trial to assess the effect of intravenous iron isomaltoside on exercise capacity, muscle strength, cognition and quality of life in iron-deficient heart transplant recipients.

Enrollment: 102 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Cardiac allograft.
• Presentation at least one year after heart transplantation.
• 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 between 18 and 80 years.
• Informed consent obtained and documented according to Good Clinical Practice (GCP), and national/regional regulations.

Exclusion 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. estimated glomerular filtration rate < 15 ml/min or on renal replacement therapy
• Planned cardiac surgery or angioplasty within 6 months
• Planned major surgery within 6 months
• Medical history of unresolved cancer (except for basal cell carcinoma)
• Treatment with systemic steroids more than the equivalent of 10 mg Prednisone/day at the time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent
• Any uncontrolled endocrine disorder except type 2 diabetes
• Pregnancy
• On erythropoietin analogues
• Known sensitivity or intolerance to iron isomaltoside or other parenteral iron preparations
• Intravenous iron supplement within 6 months prior to inclusion
• On oral iron substitution (unless the subject agrees to stop treatment prior to randomisation)
• Ongoing rejections or infections
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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102 participants in 2 patient groups, including a placebo group

Iron isomaltoside 1000

Active Comparator group

Description:

The active drug, iron isomaltoside 1000 will be administered as a single, intravenous infusion of 20 mg/kg body weight (rounded off to the nearest 100 mg) dissolved in 100 ml NaCl as recommended by the drug manufacturer ("on-label" treatment).

Treatment:

Drug: Iron Isomaltoside 1000

Placebo

Placebo Comparator group

Description:

Patients allocated to placebo will receive an intravenous infusion of 100 ml NaCl 0.9%

Treatment:

Other: Placebo: NaCl 0,9%