Iron Status Assessment in Geriatric Elderly

Официальное название

Predicting Iron Deficiency and Related Iron Parameters Outside Inflammation in Hospitalized Elderly Patients: A Prospective Study

Обзор

In elderly adults, anemia is common and multifactorial. Inflammation, which is frequently observed in hospitalized elderly patients, profoundly alters iron metabolism, making it difficult to accurately assess true iron status. The objective of this study is to identify a predictive model that can estimate iron deficiency status in the absence of inflammation using transferrin saturation (TSAT) measured during an inflammatory phase. This model could help distinguish true iron deficiency from anemia of inflammation, improve patient management, and reduce decision-making delays. The study will be conducted in two distinct phases: a pilot phase involving up to 200 patients at a single center in France, followed by a main phase involving 1,523 patients across multiple centers in France. Participants will be adults aged over 75 years who are hospitalized in a geriatric ward and present with an acute inflammatory episode (C-reactive protein \[CRP\] \> 50 mg/L). In addition to routine analyses performed during hospitalization, supplementary laboratory analyses will be carried out. Following admission in hospital, patients will receive standard medical care. Upon admission or on the following day, patients, their trusted representative, or relatives will be informed about the study. If eligibility criteria are met, the patient will be enrolled. Research-specific laboratory analyses will be performed on blood samples collected at 4 times: * the day after admission; * when CRP \< 20 mg/L (pilot phase only); * when CRP \< 10 mg/L; * five days after a CRP \< 10 mg/L. These additional analyses will not require another blood sample, as they will be performed on samples collected as part of routine clinical care. They constitute the main research specific intervention.

Подробное описание

In elderly adults, anemia is common and multifactorial. Inflammation, which is frequently observed in hospitalized elderly patients, profoundly alters iron metabolism, making it difficult to accurately assess true iron status.

The objective of this study is to identify a predictive model that can estimate iron deficiency status in the absence of inflammation using transferrin saturation (TSAT) measured during an inflammatory phase. This model could help distinguish true iron deficiency from anemia of inflammation, improve patient management, and reduce decision-making delays.

The study will be conducted in two distinct phases:

* Pilot phase: A prospective, observational, single-center study enrolling up to 200 patients or conducted over a maximum recruitment period of one year, whichever occurs first. * Main phase: A prospective, observational, multicenter study with the consecutive enrollment of 1,523 patients, including patients enrolled during the pilot phase.

The primary objective of the pilot phase is to estimate the proportion of patients with iron deficiency, defined as a transferrin saturation (TSAT) \< 20%, in order to confirm the prevalence assumption that will be used in the sample size calculation for the development of a predictive model of iron deficiency in the absence of inflammation.

The primary objective of the main phase is to develop and validate a predictive model for iron deficiency, defined according to the TSAT threshold in a non-inflammatory setting, with non-inflammation defined as a C-reactive protein (CRP) level \< 10 mg/L (or \< 20 mg/L depending on results of the pilot phase). The model will be based on measurements obtained during an acute inflammatory state in order to predict iron deficiency.

Eligible participants will be patients aged over 75 years who are hospitalized and present an acute inflammatory episode (CRP \> 50 mg/L).

In addition to the routine examinations performed during hospitalization, supplementary analyses will be conducted. After admission (Day -1), patients will receive standard care from the medical team. On the day of admission (Day -1) or the following day (Day 0), patients, their trusted representatives, or relatives will be informed about the study. If the patient fulfils the eligibility criteria, he will be enrolled in the study.

Research-specific analyses will be performed on the following blood samples:

* Day 0 : blood tests (pilot phase and main study): reticulocyte count, reticulocyte hemoglobin content (Ret-He), percentage of hypochromic red blood cells, Delta-He, serum iron, transferrin, transferrin saturation (TSAT, %), ferritin, soluble transferrin receptor, and hepcidin. * When C-reactive protein (CRP) is \< 20 mg/L (pilot phase only): reticulocyte count, reticulocyte hemoglobin content, percentage of hypochromic red blood cells, Delta-He, serum iron, transferrin, transferrin saturation (%), ferritin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, albumin, and creatine phosphokinase. * When CRP is \< 10 mg/L (pilot phase and main study): reticulocyte count, reticulocyte hemoglobin content, percentage of hypochromic red blood cells, Delta-He, serum iron, transferrin, transferrin saturation (%), ferritin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, albumin, and creatine phosphokinase. * Five days after a CRP value \< 10 mg/L (pilot phase and main study, optional): reticulocyte count, reticulocyte hemoglobin content, percentage of hypochromic red blood cells, Delta-He, serum iron, transferrin, transferrin saturation (%), ferritin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, albumin, and creatine phosphokinase.

These additional analyses will be performed using routine blood samples collected during standard clinical monitoring and will not require any additional blood samples. They constitute the main research-specific intervention beyond standard clinical practice.

The objective is to develop a simple and validated tool to estimate transferrin saturation (TSAT), and potentially ferritin levels, in the absence of inflammation using data obtained during the acute inflammatory phase. This tool could help shorten hospital stays, optimize iron therapy prescribing, and improve the management of hospitalized elderly patients.

Вмешательства

• Диагностический тест Analysis of biological parameters
  Research-specific analyses will be performed on the following blood samples: * Day 0 : reticulocyte count, reticulocyte hemoglobin content (Ret-He), percentage of hypochromic red blood cells, Delta-He, serum iron, transferrin, transferrin saturation (TSAT, %), ferritin, soluble transferrin receptor, and hepcidin. * CRP \< 20 mg/L (pilot phase only): reticulocyte count, reticulocyte hemoglobin content, percentage of hypochromic red blood cells, Delta-He, serum iron, transferrin, TSAT (%), ferrit

Первичные конечные точки

• Proportion of patients with iron deficiency, defined as transferrin saturation < 20% (pilot phase) [Срок оценки: From enrollment to the end of study at 4 weeks maximum]
• To develop a predictive model for iron deficiency, defined by TSAT under non-inflammatory conditions (defined as CRP<10 mg/L or <20 mg/L, depending on results of pilot phase), using measurements obtained during acute inflammatory episode (main phase) [Срок оценки: From enrollment to the end of study at 4 weeks maximum]

Вторичные конечные точки (5)

• Proportion of patients with CRP < 20 mg/L and proportion of patients with CRP < 10 mg/L in the study population (pilot phase) [Срок оценки: From enrollment to the end of study at 4 weeks maximum]
• Among the clinically relevant variables, and within subgroups of patients with CRP < 20 mg/L and < 10 mg/L (pilot phase), to examine a/the collinearity structure among potential predictors ; b/the distribution of categorical variables [Срок оценки: From enrollment to the end of study at 4 weeks maximum]
• To assess the correlation between transferrin saturation measured during an inflammatory state and transferrin saturation measured under non-inflammatory conditions. [Срок оценки: From enrollment to the end of study at 4 weeks maximum]
• To develop and validate a predictive model for iron deficiency, defined by ferritin levels under non-inflammatory conditions, with non-inflammation defined as CRP < 10 mg/L (or < 20 mg/L, depending on the results of the pilot phase). [Срок оценки: From enrollment to the end of study at 4 weeks maximum]
• To assess the evolution of iron status parameters when CRP < 10mg/l and 5 days post CRP < 10mg/l. [Срок оценки: From enrollment to the end of study at 4 weeks maximum]

Критерии участия

Критерии включения

• Age ≥ 75 years.
• Hospitalization with CRP > 50 mg/L at admission.
• Non-opposition expressed by patient or legally authorized representative

Критерии исключения

• Advanced chronic kidney disease (estimated glomerular filtration rate < 30 mL/min/1.73 m²) or chronic dialysis.
• Severe hepatic impairment (Child-Pugh score B or C).
• Severe hematological disorders (active hematologic malignancy or known myelodysplastic syndrome) or known iron metabolism disorders that may bias the study results (e.g., thalassemia, advanced hemochromatosis).
• Hemoglobin < 9g/L
• Treatment with intravenous iron within 12 weeks or oral iron within 4 weeks prior to enrollment.
• Blood transfusion within 3 months prior to enrollment
• Ongoing treatment with erythropoiesis-stimulating agents.
• Ongoing cytotoxic chemotherapy.
• Active bleeding at the time of enrollment.
• Very limited life expectancy or inability to ensure follow-up (end-of-life care).
• Participation in another investigational medicinal product study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 1 центр

• Centre Hospitalier Universitaire d'Orléans — Orléans

Публикации

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• Carmona C, Bewick T, Macduff N, Thomas A; Guideline Committee. Suspected acute respiratory infection in over 16s: assessment at first presentation and initial management-summary of NICE guidance. BMJ. 2024 Mar 11;384:q339. doi: 10.1136/bmj.q339. No abstract available. PMID 38467421
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• Namaste SM, Rohner F, Huang J, Bhushan NL, Flores-Ayala R, Kupka R, Mei Z, Rawat R, Williams AM, Raiten DJ, Northrop-Clewes CA, Suchdev PS. Adjusting ferritin concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr. 2017 Jul;106(Suppl 1):359S-371S. doi: 10.3945/ajcn.116.141762. Epub 2017 Jun 14. PMID 28615259
• McSorley ST, Tham A, Jones I, Talwar D, McMillan DC. Regression Correction Equation to Adjust Serum Iron and Ferritin Concentrations Based on C-Reactive Protein and Albumin in Patients Receiving Primary and Secondary Care. J Nutr. 2019 May 1;149(5):877-883. doi: 10.1093/jn/nxz008. PMID 31050746
• McSorley ST, Jones I, McMillan DC, Talwar D. Quantitative data on the magnitude of the systemic inflammatory response and its relationship with serum measures of iron status. Transl Res. 2016 Oct;176:119-26. doi: 10.1016/j.trsl.2016.05.004. Epub 2016 Jun 6. PMID 27337525

Идентификаторы

NCT: NCT07739524 · CHUO-2025-18

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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