Heart Transplant RecipientsPhase 2/3IronICNCT03662789
Intravenous Iron Supplement for Iron Deficiency in Cardiac Transplant Recipients
A Phase 2/3 study testing Iron Isomaltoside 1000 in people with Heart Transplant Recipients, run by Oslo University Hospital at 1 site in Norway.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Transplant Recipients
- What is being tested?
- Iron Isomaltoside 1000
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- 1 siteNorway
- Study dates
- 25 Apr 2018to 27 Feb 2020
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 20Show fewer
- 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 locations and contacts
1 site in 1 country.
About this study
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
Read the 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
- Being tested
- Iron Isomaltoside 1000, Placebo: NaCl 0,9%
- Keywords
- Heart transplant, Iron deficiency, Intravenous iron supplement, Peak oxygen consumption, Cardiopulmonary exercise test, Cognitive function, Muscle strength
- Medical subject headings
- Iron Deficiencies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Iron Isomaltoside 1000Drug
Also called Monofer B03AC-
Intravenous infusion
Placebo: NaCl 0,9%Other
Intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Iron isomaltoside 1000 | Active comparator | 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). Receives: Drug: Iron Isomaltoside 1000 |
| Placebo | Placebo comparator | Patients allocated to placebo will receive an intravenous infusion of 100 ml NaCl 0.9% Receives: Other: Placebo: NaCl 0,9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Oxygen Consumption
The primary endpoint will be the baseline-adjusted between-group difference in peak oxygen consumption as measured on a treadmill exercise test
Measured: 6 months after intervention
Secondary outcomes (6)
Iron Deficiency
The number of patients with absolute or functional iron deficiency
Measured: 6 months after intervention
Muscle Strength
Baseline-adjusted muscle strength as measured by a hand-grip dynamometer
Measured: 6 months after intervention
Health Related Quality of Life: SF-36, Physical Component Summary (PCS)
Baseline-adjusted quality of life as assessed with the 36-item short form survey (SF-36), which measures each of the following 8 health domains: 1= general health, 2= physical function, 3= role physical, 4= bodily pain, 5= vitality, 6= social function, 7= role emotional, 8= mental health. Total score for each domain are scaled 0 (minimum) to 100 (maximum), where higher scores represented higher level of functioning. Two norm-based sum scores, the physical and the mental component summaries with a mean of 50±10, were generated from the eight scale scores using a T-score transformation. Higher scores represented higher level of functioning.
Measured: 6 months after intervention
N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)
The between-group difference in baseline-adjusted NT-proBNP
Measured: 6 months after intervention
Cardiac Troponin T (TnT)
The between-group difference in baseline-adjusted TnT
Measured: 6 months after intervention
Health Related Quality of Life: SF-36, Mental Component Summary (MCS)
Baseline-adjusted quality of life as assessed with the 36-item short form survey (SF-36), which measures each of the following 8 health domains: 1= general health, 2= physical function, 3= role physical, 4= bodily pain, 5= vitality, 6= social function, 7= role emotional, 8= mental health. Total score for each domain are scaled 0 (minimum) to 100 (maximum), where higher scores represented higher level of functioning. Two norm-based sum scores, the physical and the mental component summaries with a mean of 50±10, were generated from the eight scale scores using a T-score transformation. Higher scores represented higher level of functioning.
Measured: 6 months after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2018
- Study start25 Apr 2018
- Primary completion27 Feb 2020
- Study completion27 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart Transplant RecipientsStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, placebo controlled, parallel group, double blind design
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Pharmacosmos A/S
- Responsible party
- Principal investigator, Lars Gullestad, Oslo University Hospital
- Investigators
- Lars Gullestad, MD, PhD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03662789
- Sponsor's protocol ID
- IronIC
- Acronym
- IronIC
- Status last verified
- Apr 2021
- First submitted
- 17 Apr 2018
- Last updated
- 25 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33612360Burker BS, Brautaset Englund KV, Myrdal Ostby C, Andersson S, Gullestad L, Broch K. Cognitive Function Among Heart Transplant Recipients Before and After Intravenous Iron Supplement for Iron Deficiency: Results From a Randomized, Placebo-Controlled, Double-Blind Treatment Trial. Clin Transplant. 2025 Nov;39(11):e70370. doi: 10.1111/ctr.70370.
PubMed 41182019
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravenous Iron Supplement for Iron Deficiency in Cardiac Transplant Recipients
- ClinicalTrials.gov ID
- NCT03662789
- Acronym / sponsor ID
- IronIC / IronIC
- Conditions
- Heart Transplant Recipients
- Keywords
- Heart transplant, Iron deficiency, Intravenous iron supplement, Peak oxygen consumption, Cardiopulmonary exercise test, Cognitive function, Muscle strength
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- Pharmacosmos A/S
- Study start
- 25 Apr 2018 (actual)
- Primary completion
- 27 Feb 2020 (actual)
- Study completion
- 27 Feb 2020 (actual)
- First posted
- 7 Sep 2018 (actual)
- Results
- Posted 25 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, placebo controlled, parallel group, double blind design
| Arm | Type | Receives |
|---|---|---|
| Iron isomaltoside 1000 | Active comparator | Drug: Iron Isomaltoside 1000The 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). |
| Placebo | Placebo comparator | Other: Placebo: NaCl 0,9%Patients allocated to placebo will receive an intravenous infusion of 100 ml NaCl 0.9% |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (20 listed)
- Anaemia (Haemoglobin < 100 mg/l)
- Haemochromatosis
- Haemosiderosis
- Porphyria cutanea tarda
- Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Iron Isomaltoside 1000Also: Monofer B03AC-Intravenous infusion | Drug | Iron isomaltoside 1000 |
| Placebo: NaCl 0,9%Intravenous infusion | Other | Placebo |
Primary outcome
Peak Oxygen Consumption
Time frame: 6 months after intervention
The primary endpoint will be the baseline-adjusted between-group difference in peak oxygen consumption as measured on a treadmill exercise test
6 secondary outcomes
Iron Deficiency
Time frame: 6 months after intervention
Muscle Strength
Time frame: 6 months after intervention
Health Related Quality of Life: SF-36, Physical Component Summary (PCS)
Time frame: 6 months after intervention
N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)
Time frame: 6 months after intervention
Cardiac Troponin T (TnT)
Time frame: 6 months after intervention
Health Related Quality of Life: SF-36, Mental Component Summary (MCS)
Time frame: 6 months after intervention
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 33612360Brautaset 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.
- Derived from this study: PubMed 41182019Burker BS, Brautaset Englund KV, Myrdal Ostby C, Andersson S, Gullestad L, Broch K. Cognitive Function Among Heart Transplant Recipients Before and After Intravenous Iron Supplement for Iron Deficiency: Results From a Randomized, Placebo-Controlled, Double-Blind Treatment Trial. Clin Transplant. 2025 Nov;39(11):e70370. doi: 10.1111/ctr.70370.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lars Gullestad, MD, PhD principal investigator
Oslo University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Iron Isomaltoside 1000 in people with Heart Transplant Recipients, run by Oslo University Hospital at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak Oxygen Consumption (time frame: 6 months after intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03662789, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2021.