Trial reportHaematologica2021
Intravenous iron preparations transiently generate non-transferrin-bound iron from two proposed pathways.
Trial report in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 citations in OpenAlex.
- Pooled it
- A systematic literature review and meta-analysis of the incidence of serious or severe hypersensitivity reactions after administration of ferric derisomaltose or ferric carboxymaltose.International journal of clinical pharmacy · 2023Pooled it
- Effect of correcting iron deficiency on the risk of serious infection in heart failure: Insights from the IRONMAN trial.European journal of heart failure · 2025Trial
- Intravenous ferric derisomaltose versus saccharated ferric oxide for iron deficiency anemia associated with menorrhagia: a randomized, open-label, active-controlled, noninferiority study.International journal of hematology · 2022Trial
- Single-dose intravenous ferric carboxymaltose infusion versus multiple fractionated doses of intravenous iron sucrose in the treatment of post-operative anaemia in colorectal cancer patients: a randomised controlled trial.Blood transfusion = Trasfusione del sangue · 2022Trial
- Analysis of oxidative stress, inflammation and endothelial function following intravenous iron in chronic kidney disease in the Iron and Heart Trial.Scientific reports · 2022Trial
- Sulfide silver autometallography to differentiate the ultrastructural localization of iron-carbohydrate complexes inside macrophages.Scientific reports · 2025Article
- Article
- Challenging Traditional ADME Assumptions for Physiologically Based Pharmacokinetic Models for Intravenous Administration of Iron-Carbohydrate Nanomedicines: Potential Utility of Gold Nanoparticle Models as a Roadmap.Clinical pharmacokinetics · 2025Review
- The Relationship Between Non-Transferrin-Bound Iron (NTBI), Labile Plasma Iron (LPI), and Iron Toxicity.International journal of molecular sciences · 2025Review
- A whole-body mechanistic physiologically-based pharmacokinetic modeling of intravenous iron.Drug delivery and translational research · 2025Article
- Intravenous iron in chronic kidney disease without anaemia but iron deficiency: A scoping review.World journal of nephrology · 2025Review
- Oral and Intravenous Iron Therapy.Advances in experimental medicine and biology · 2025Review
- Intravenous iron therapy results in rapid and sustained rise in myocardial iron content through a novel pathway.European heart journal · 2024Observational
- Iron deficiency and supplementation in heart failure.Nature reviews. Cardiology · 2024Review
- Iron Dyshomeostasis and Mitochondrial Function in the Failing Heart: A Review of the Literature.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024Review
- Probing Subcellular Iron Availability with Genetically Encoded Nitric Oxide Biosensors.Biosensors · 2022Article
- Kupffer Cells and Blood Monocytes Orchestrate the Clearance of Iron-Carbohydrate Nanoparticles from Serum.International journal of molecular sciences · 2022Article
- Criticality of Surface Characteristics of Intravenous Iron-Carbohydrate Nanoparticle Complexes: Implications for Pharmacokinetics and Pharmacodynamics.International journal of molecular sciences · 2022Review
- Rhabdomyolysis after Intravenous Ferric Gluconate: A Case Report.European journal of case reports in internal medicine · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Intravenous iron-carbohydrate complex preparations (IVIPs) are non-interchangeable pro-drugs: their pharmacokinetics (PK) varies determined by semi-crystalline iron core and carbohydrate shell structures, influences pharmacodynamics (PD) and thus efficacy and safety. Examining PK/PD relationships of 3 IVIPs we identify a two-pathway model of transient NTBI generation following single dose administration. 28 hypoferremic non-anemic patients randomized to 200mg iron as ferric carboxymaltose (Fe-carboxymaltose), iron sucrose (Fe-sucrose), iron isomaltoside 1000 (Fe-isomaltoside-1000), n=8/arm, or placebo, n=4, on a 2-week PK/PD study, had samples analysed for total serum iron, IVIP-iron, transferrin-bound iron (TBI) by HPLC-ICP-MS, transferrin saturation (TSAT), serum ferritin (s-Ferritin) by standard methods, non-TBI (NTBI) and hepcidin as published before. IVIP-dependent increases in these parameters returned to baseline in 48-150h, except for s-Ferritin and TSAT. NTBI was low with Fe-isomaltoside-1000 (0.13µM at 8h), rapidly increased with Fe-sucrose (0.8µM at 2h, 1.25µM at 4h), and delayed for Fe-carboxymaltose (0.57µM at 24h). NTBI AUCs were 7-fold greater for Fe-carboxymaltose and Fe-sucrose than for Fe-isomaltoside-1000. Hepcidin peak time varied, but not AUC or mean levels. s-Ferritin levels and AUC were highest for Fe-carboxymaltose and greater than placebo for all IVIPs. We propose 2 mechanisms for the observed NTBI kinetics: rapid and delayed NTBI appearance consistent with direct (circulating IVIP-to-plasma) and indirect (IVIP-to-macrophage-to-plasma) iron release based on IVIP plasma half-life and s-Ferritin dynamics. IVIPs generate different, broadly stability- and PK-dependent, NTBI and s-Ferritin signatures, which may influence iron bioavailability, efficacy and safety. Longer-term studies should link NTBI exposure to subsequent safety and efficacy parameters and potential clinical consequences.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.