Intravenous Iron Supplement for Iron Deficiency in Cardiac Transplant Recipients

NCT ID: NCT03662789

Last Updated: 2021-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-25
• Study Completion Date: 2020-02-27

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.

Conditions

Heart Transplant Recipients

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Iron isomaltoside 1000

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).

Group Type: ACTIVE_COMPARATOR

Iron Isomaltoside 1000

Intervention Type: DRUG

Intravenous infusion

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo: NaCl 0,9%

Intervention Type: OTHER

Intravenous infusion

Interventions

Iron Isomaltoside 1000

Intravenous infusion

Intervention Type: DRUG

Placebo: NaCl 0,9%

Intravenous infusion

Intervention Type: OTHER

Other Intervention Names

Monofer B03AC-

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharmacosmos A/S

INDUSTRY

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Lars Gullestad

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lars Gullestad, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Oslo University Hospital

Locations

Oslo university Hospital, Rikshospitalet

Oslo, , Norway

Countries

Norway

References

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.

Reference Type: BACKGROUND

PMID: 33612360 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

IronIC

Identifier Type: -

Identifier Source: org_study_id