A Phase 2/3 interventional study of Iron Isomaltoside 1000 and Placebo: NaCl 0,9% in Heart Transplant Recipients, sponsored by Oslo University Hospital. Completed at 1 site in Norway. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2021-05-25.
Sponsored by Oslo University Hospital · Phase 2/3, Interventional, and Treatment
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
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.
644 studies on the registry are indexed under Anemia, Iron-Deficiency; 105 are open to participants now.
This study's enrollment of 102 is close to the median of 100 across 503 interventional studies indexed under Anemia, Iron-Deficiency.
Browse Anemia, Iron-Deficiency studies →Oslo University Hospital is the lead sponsor of 810 studies on the registry; 148 are open to participants now.
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Exclusion Criteria:
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).
Drug: Iron Isomaltoside 1000
Patients allocated to placebo will receive an intravenous infusion of 100 ml NaCl 0.9%
Other: Placebo: NaCl 0,9%
Intravenous infusion
Also known as: Monofer B03AC-
Intravenous infusion
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
Time frame: 6 months after intervention
Iron Deficiency
The number of patients with absolute or functional iron deficiency
Time frame: 6 months after intervention
Muscle Strength
Baseline-adjusted muscle strength as measured by a hand-grip dynamometer
Time frame: 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.
Time frame: 6 months after intervention
N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)
The between-group difference in baseline-adjusted NT-proBNP
Time frame: 6 months after intervention
Cardiac Troponin T (TnT)
The between-group difference in baseline-adjusted TnT
Time frame: 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.
Time frame: 6 months after intervention
| Milestone | Iron Isomaltoside 1000 | Placebo |
|---|---|---|
| Started | 52 | 50 |
| Completed | 47 | 43 |
| Not completed | 5 | 7 |
| Withdrew: Lost to follow-up | 1 | 2 |
| Withdrew: Could not perform treadmill test | 4 | 4 |
| Withdrew: Death | 0 | 1 |
The primary endpoint will be the baseline-adjusted between-group difference in peak oxygen consumption as measured on a treadmill exercise test
| ml/kg/min | Iron Isomaltoside 1000 | Placebo |
|---|---|---|
| Peak Oxygen Consumption | 23.9 ± 6.6 | 22.0 ± 6.1 |
The number of patients with absolute or functional iron deficiency
| Participants | Iron Isomaltoside 1000 | Placebo |
|---|---|---|
| Iron Deficiency | 7 | 40 |
Baseline-adjusted muscle strength as measured by a hand-grip dynamometer
| kg | Iron Isomaltoside 1000 | Placebo |
|---|---|---|
| Muscle Strength | 40 ± 13 | 38 ± 12 |
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.
| t-score | Iron Isomaltoside 1000 | Placebo |
|---|---|---|
| Health Related Quality of Life: SF-36, Physical Component Summary (PCS) | 49 (42 to 55) | 45 (37 to 53) |
The between-group difference in baseline-adjusted NT-proBNP
| ng/l | Iron Isomaltoside 1000 | Placebo |
|---|---|---|
| N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) | 421 (134 to 807) | 349 (237 to 706) |
The between-group difference in baseline-adjusted TnT
| ng/l | Iron Isomaltoside 1000 | Placebo |
|---|---|---|
| Cardiac Troponin T (TnT) | 13.0 (8.0 to 25.8) | 15.0 (8.0 to 24.3) |
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.
| t-score | Iron Isomaltoside 1000 | Placebo |
|---|---|---|
| Health Related Quality of Life: SF-36, Mental Component Summary (MCS) | 56 (49 to 60) | 53 (48 to 58) |
Collected over 6 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Iron Isomaltoside 1000 | 0/52 (0%) | 5/52 (9.6%) | 22/52 (42.3%) |
| Placebo | 1/50 (2%) | 12/50 (24%) | 18/50 (36%) |
| Event | Iron Isomaltoside 1000 | Placebo |
|---|---|---|
| InfectionInfections and infestations | 0/52 | 8/50 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 2/52 | 0/50 |
| FractureMusculoskeletal and connective tissue disorders | 1/52 | 1/50 |
| HyperthyreosisEndocrine disorders | 0/52 | 1/50 |
| Heart failureCardiac disorders | 0/52 | 1/50 |
| DeceasedCardiac disorders | 0/52 | 1/50 |
| CholelitiasisHepatobiliary disorders | 1/52 | 0/50 |
| ST-elevation myocardial infarctionCardiac disorders | 1/52 | 0/50 |
| Event | Iron Isomaltoside 1000 | Placebo |
|---|---|---|
| InfectionInfections and infestations | 12/52 | 5/50 |
| BleedingBlood and lymphatic system disorders | 0/52 | 4/50 |
| Musculoskeletal painMusculoskeletal and connective tissue disorders | 1/52 | 3/50 |
| GoutMusculoskeletal and connective tissue disorders | 1/52 | 2/50 |
| Generalized RashSkin and subcutaneous tissue disorders | 2/52 | 0/50 |
| HerniaGastrointestinal disorders | 0/52 | 1/50 |
| RefluxGastrointestinal disorders | 0/52 | 1/50 |
| Local rashSkin and subcutaneous tissue disorders | 0/52 | 1/50 |
| PancreatitisGastrointestinal disorders | 0/52 | 1/50 |
| Hair lossSkin and subcutaneous tissue disorders | 1/52 | 0/50 |
| Age, Categorical(Participants) | Iron Isomaltoside 1000 | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 34 | 39 | 73 |
| >=65 years | 18 | 11 | 29 |
| Age, Continuous(years) | Iron Isomaltoside 1000 | Placebo | Total |
|---|---|---|---|
| Mean | 55 ± 15 | 55 ± 14 | 55 ± 14 |
| Sex: Female, Male(Participants) | Iron Isomaltoside 1000 | Placebo | Total |
|---|---|---|---|
| Female | 18 | 19 | 37 |
| Male | 34 | 31 | 65 |
| Race and Ethnicity Not Collected(Participants) | Iron Isomaltoside 1000 | Placebo | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| Region of Enrollment(participants) | Iron Isomaltoside 1000 | Placebo | Total |
|---|---|---|---|
| Norway | 52 | 50 | 102 |
| Peak oxygen consumption(ml/kg/min) | Iron Isomaltoside 1000 | Placebo | Total |
|---|---|---|---|
| Mean | 24.3 ± 7.3 | 22.3 ± 6.0 | 23.4 ± 6.8 |
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Oslo University Hospital