Acute Inflammatory Response, Elderly, Iron Deficiency
Conditions
Keywords
Transferrin Saturation, Iron Parameters, Inflammation, Elderly, Predictive model
Brief summary
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.
Detailed description
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.
Interventions
DIAGNOSTIC_TESTAnalysis 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 (%), ferritin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), total bilirubin, albumin, and creatine phosphokinase (CPK). * CRP \< 10 mg/L: reticulocyte count, reticulocyte hemoglobin content, percentage of hypochromic red blood cells, Delta-He, serum iron, transferrin, TSAT (%), ferritin, , AST, ALT, AP, total bilirubin, albumin, and CPK. * 5 days after CRP \< 10 mg/L: same as CRP \< 10 mg/L
Sponsors
Centre Hospitalier Régional d'Orléans
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
75 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 75 years. 2. Hospitalization with CRP \> 50 mg/L at admission. 3. Non-opposition expressed by patient or legally authorized representative
Exclusion criteria
1. Advanced chronic kidney disease (estimated glomerular filtration rate \< 30 mL/min/1.73 m²) or chronic dialysis. 2. Severe hepatic impairment (Child-Pugh score B or C). 3. 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). 4. Hemoglobin \< 9g/L 5. Treatment with intravenous iron within 12 weeks or oral iron within 4 weeks prior to enrollment. 6. Blood transfusion within 3 months prior to enrollment 7. Ongoing treatment with erythropoiesis-stimulating agents. 8. Ongoing cytotoxic chemotherapy. 9. Active bleeding at the time of enrollment. 10. Very limited life expectancy or inability to ensure follow-up (end-of-life care). 11. Participation in another investigational medicinal product study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | From enrollment to the end of study at 4 weeks maximum | Transferrin saturation (TSAT) will be measured at baseline and when CRP \< 10 mg/L (or \< 20 mg/L, depending on results of the pilot phase). Iron deficiency will be defined as a TSAT \< 20%. The predictive performance of the model for estimating TSAT under non-inflammatory conditions and the agreement between predicted and observed TSAT values under non-inflammatory conditions will be assessed. |
| Proportion of patients with iron deficiency, defined as transferrin saturation < 20% (pilot phase) | From enrollment to the end of study at 4 weeks maximum | To estimate the proportion of patients with iron deficiency, defined as transferrin saturation (TSAT) \< 20%, in order to validate the prevalence assumption that will be used in the sample size calculation for the development of a predictive model of iron deficiency under non-inflammatory conditions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). | From enrollment to the end of study at 4 weeks maximum | Ferritin will be assessed at baseline and when CRP is \< 10 mg/L (or \< 20 mg/L, depending on the results of the pilot phase). Iron deficiency will be defined by a ferritin level \< 100 µg/L. The predictive performance of the model for estimating ferritin under non-inflammatory conditions and the agreement between predicted and observed ferritin values under non-inflammatory conditions will be assessed. |
| 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 | From enrollment to the end of study at 4 weeks maximum | For collinearity: Associations between candidate predictors will first be assessed through bivariate analyses (Spearman's or Pearson's correlation coefficient for two continuous variables, Cramér's V for two categorical variables, and point-biserial correlation for a continuous/binary variable pair), using a predefined alert threshold of \|r\| or V \> 0.7. A variance inflation factor (VIF) will then be calculated for each predictor retained after this initial step; variables with a VIF \> 5 will be excluded. For rare categories: Frequency distributions will be examined for each categorical variable. A category will be considered too rare if it represents less than 5% of the subgroup sample size. |
| Proportion of patients with CRP < 20 mg/L and proportion of patients with CRP < 10 mg/L in the study population (pilot phase) | From enrollment to the end of study at 4 weeks maximum | To estimate the proportion of patients with CRP \< 20 mg/L and the proportion of patients with CRP \< 10 mg/L, in order to refine the study population for the development of the predictive model of iron deficiency under non-inflammatory conditions. |
| To assess the evolution of iron status parameters when CRP < 10mg/l and 5 days post CRP < 10mg/l. | From enrollment to the end of study at 4 weeks maximum | Iron status parameters assessed when CRP \< 10mg/l and 5 days post CRP \< 10mg/l. |
| To assess the correlation between transferrin saturation measured during an inflammatory state and transferrin saturation measured under non-inflammatory conditions. | From enrollment to the end of study at 4 weeks maximum | Correlation between transferrin saturation measured during inflammation (baseline sample) and transferrin saturation measured once C-reactive protein (CRP) levels have decreased to \< 10 mg/L. |
Countries
France
Contacts
CONTACTMoez JALLOULI, Principal Investigator
CONTACTFanny LOUAT
Outcome results
None listed