Clinical trial NCT03662789: Intravenous Iron Supplement for Iron Deficiency in Cardiac Transplant Recipients
Official title: Intravenous Iron Supplement for Iron Deficiency in Cardiac Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Heart Transplant Recipients
Keywords: Heart transplant
Iron deficiency
Intravenous iron supplement
Peak oxygen consumption
Cardiopulmonary exercise test
Cognitive function
Muscle strength
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Pharmacosmos A/S
First posted: 2018-09-07
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, placebo controlled, parallel group, double blind design
Primary purpose: TREATMENT

Brief summary: 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Peak Oxygen Consumption
timeFrame: 6 months after intervention
Secondary outcomes:
measure: Iron Deficiency
timeFrame: 6 months after intervention
measure: Muscle Strength
timeFrame: 6 months after intervention
measure: Health Related Quality of Life: SF-36, Physical Component Summary (PCS)
timeFrame: 6 months after intervention
measure: N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)
timeFrame: 6 months after intervention
measure: Cardiac Troponin T (TnT)
timeFrame: 6 months after intervention
measure: Health Related Quality of Life: SF-36, Mental Component Summary (MCS)
timeFrame: 6 months after intervention
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo university Hospital, Rikshospitalet
Study officials:
affiliation: Oslo University Hospital
name: Lars Gullestad, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brautaset Englund KV, Ostby CM, Rolid K, Gude E, Andreassen AK, Gullestad L, Broch K. Intravenous iron supplement for iron deficiency in cardiac transplant recipients (IronIC): A randomized clinical trial. J Heart Lung Transplant. 2021 May;40(5):359-367. doi: 10.1016/j.healun.2021.01.1390. Epub 2021 Jan 23.