Intravenous iron supplement for iron deficiency in cardiac transplant recipients (IronIC): A randomized clinical trial
Heart transplant recipients have reduced exercise capacity despite preserved graft function. The IronIC trial was designed to test the hypothesis that intravenous iron therapy would improve peak oxygen consumption in these patients.
METHODS AND RESULTS:This randomized, placebo-controlled, double-blind trial was performed at our national center for heart transplantation. One hundred and 2 heart transplant recipients with a serum ferritin <100 µg/liter or 100 to 300 µg/liter, in combination with transferrin saturation of <20%, and hemoglobin level >100 g/liter were enrolled ≥1 year after transplantation. A cardiopulmonary exercise test was performed before administration of the study drug and at 6 months follow-up. The primary endpoint was peak oxygen consumption. Key secondary outcomes included iron status, handgrip strength, quality of life, and safety. Fifty-two patients were randomized to receive ferric derisomaltose 20 mg/kg, and 50 to placebo. The between-group difference in baseline-adjusted peak oxygen consumption was 0.3 ml/kg/min (95% confidence interval -0.9 to 1.4, p = 0.66). In patients with a baseline ferritin <30 µg/liter, peak oxygen consumption was significantly higher in the ferric derisomaltose arm. At 6 months, iron stores were restored in 86% of the patients receiving ferric derisomaltose vs 20% in patients receiving placebo (p < 0.001). Quality of life was significantly better in patients receiving ferric derisomaltose. Twenty-seven adverse events occurred in the intravenous iron group vs 30 in the placebo group (p = 0.39).
CONCLUSION:Intravenous iron treatment did not improve peak oxygen consumption in heart transplant recipients with ferritin <100 µg/liter or 100 to 300 µg/liter in combination with transferrin saturation <20%.
TRIAL REGISTRATION NUMBER:http//www.clinicaltrials.gov identifier NCT03662789.
CET Conclusion
| Reviewer: | Dr Liset Pengel, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford |
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| Conclusion: | The double-blind, randomised controlled trial tested the hypothesis that a single intravenous infusion of ferric derisomaltose would improve peak oxygen consumption in heart transplant recipients with iron deficiency who were at least one year posttransplant. Patients were randomised according to a computer-generated randomisation list and allocation was concealed by using opaque, sealed envelopes. Double-blinding was ensured by using the following procedure: a nurse not otherwise involved in the study prepared and administered the infusion solution, the patient was blindfolded, and the injection site, syringes, and intravenous lines were all covered. The sample size calculation was based on the primary outcome peak oxygen consumption and indicated that 102 patients would provide 80% power, taking into account dropouts. Peak oxygen consumption did not differ at the 6-month follow-up. The change in health-related quality of life was greater in the intervention arm (EQ-5D-3L) compared to placebo, however this was not the case for the physical component of the SF-36. A pre-specified subgroup analysis showed that patients with very low iron at baseline (ferritin <30 mg/liter, n=12) did show an improvement in peak oxygen consumption. |
Methodological quality
| Jadad score | 5 |
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| Allocation concealment | YES |
| Data analysis | STRICT INTENTION TO TREAT |
Study Details
| Aims: | This study aimed to investigate whether intravenous iron therapy led to improvement in peak oxygen consumption in cardiac transplant patients. |
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| Interventions: | Participants were randomly assigned to either the intravenous ferric derisomaltose group or the placebo group. |
| Participants: | 52 heart transplant patients. |
| Outcomes: | The primary endpoint was peak oxygen consumption. The secondary outcomes included iron deficiency (absolute or functional), muscle strength, quality of life, cardiac function and safety. |
| Follow Up: | 6 months |
Metadata
| Funding: | Industry funding |
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| Publication type: | Multicenter Study, Randomized Controlled Trial, Randomised Controlled Trial |
| Trial registration: | ClinicalTrials.gov - NCT03662789 |
| Organ: | Heart |
| Language: | English |
| Author email: | krvbra@ous-hf.no |
| MeSH terms: | Adolescent; Adult; Aged; Aged, 80 and over; Disaccharides; Double-Blind Method; Female; Ferric Compounds; Heart Failure; Heart Transplantation; Humans; Infusions, Intravenous; Iron Deficiencies; Male; Middle Aged; Oxygen Consumption; Quality of Life; Transplant Recipients; Young Adult; Aged, 80 and Over; 0 (Disaccharides); 0 (Ferric Compounds); AHU547PI9H (Ferric Derisomaltose) |