Anemia Clinical Trial
— FIERCEOfficial title:
Intravenous Ferric Carboxymaltose Versus Oral Ferrous Sulfate Replacement in Anaemia Due to Acute Nonvariceal Gastrointestinal Bleeding (FIERCE): Protocol of a Multicentre Randomised Controlled Trial
Anemia is a frequent complication of gastrointestinal bleeding, affecting 61% of the patients. Currently, anemia caused by gastrointestinal bleeding can be treated with iron supplementation. However, the dose and route of the administration are still a question. The FIERCE clinical trial aims to compare the effect of intravenous iron supplementation and oral iron replacement on mortality, unplanned emergency visits, and hospital readmissions in multimorbid patients with acute nonvariceal gastrointestinal bleeding.
Status | Not yet recruiting |
Enrollment | 570 |
Est. completion date | February 1, 2027 |
Est. primary completion date | December 31, 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 65 Years and older |
Eligibility | Inclusion Criteria: 1. age = 65 years; 2. endoscopically proven acute nonvariceal GIB source; 3. 48 hours after the endoscopic diagnosis and/or treatment; 4. hemodynamically stable; 5. the discharge of the patient is planned; 6. hemoglobin level <10 g/dl on the day of randomisation; 7. 24 hours after the last transfusion and no need for further transfusion; 8. signed informed consent. Exclusion Criteria: 1. known hypersensitivity to iron products (mild side effects excluded); 2. previous diagnosis of iron overload [e.g., transferrin receptor saturation (TSAT) >50%, ferritin> 160 for women ng/ml, ferritin >270 ng/ml for men) or disorders of iron utilisation; 3. pregnancy or breast feeding; 4. diagnosis of iron malabsorption (at discretion of the attending clinician; e.g., severe inflammatory bowel disease, active celiac disease); 5. chronic end stage diseases (chronic heart failure-New York Heart Association Classification class 4, chronic kidney disease (eGFR <30 mL/min/1.73 m2) with or without dialysis, liver cirrhosis with Child Pugh C score, chronic kidney disease with dialysis, chronic obstructive pulmonary disease stage 4, chronic inflammatory disease, malignancies, AIDS); 6. active malignancies; 7. liver cirrhosis with known varices at high risk of bleeding - endoscopic features of high risk of variceal bleeding or liver stiffness measured by transient elastography >20 kiloPascal and platelet count <150 × 10^9 cells/L; 8. gastrointestinal tract malignancies with high risk of gastrointestinal bleeding; 9. high risk of poor compliance or no fixed abode; 10. myelo- or lymphoproliferative diseases; 11. anemia not attributable to iron deficiency (sideroblastic anaemia, aplastic anaemia, haemolytic anaemia, thalassaemia, B12 vitamin or folic acid deficiency or combination of these with IDA); 12. primary coagulation disorders (e.g. Glanzmann thrombasthenia, Von Willebrand disease, Haemophylia A, Haemophylia B); 13. the patient will be transferred to another institute after discharge (e.g. hospital, senior care center); 14. Eastern Cooperative Oncology Group (ECOG) Performance Status >2. |
Country | Name | City | State |
---|---|---|---|
Hungary | Institute for Translational Medicine, University of Pécs | Pécs |
Lead Sponsor | Collaborator |
---|---|
University of Pecs |
Hungary,
Bager P, Dahlerup JF. Randomised clinical trial: oral vs. intravenous iron after upper gastrointestinal haemorrhage--a placebo-controlled study. Aliment Pharmacol Ther. 2014 Jan;39(2):176-87. doi: 10.1111/apt.12556. Epub 2013 Nov 19. — View Citation
Cotter J, Baldaia C, Ferreira M, Macedo G, Pedroto I. Diagnosis and treatment of iron-deficiency anemia in gastrointestinal bleeding: A systematic review. World J Gastroenterol. 2020 Dec 7;26(45):7242-7257. doi: 10.3748/wjg.v26.i45.7242. — View Citation
Ferrer-Barcelo L, Sanchis Artero L, Sempere Garcia-Arguelles J, Canelles Gamir P, P Gisbert J, Ferrer-Arranz LM, Monzo Gallego A, Plana Campos L, Huguet Malaves JM, Lujan Sanchis M, Ruiz Sanchez L, Barcelo Cerda S, Medina Chulia E. Randomised clinical trial: intravenous vs oral iron for the treatment of anaemia after acute gastrointestinal bleeding. Aliment Pharmacol Ther. 2019 Aug;50(3):258-268. doi: 10.1111/apt.15327. Epub 2019 Jun 14. — View Citation
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Tolkien Z, Stecher L, Mander AP, Pereira DI, Powell JJ. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One. 2015 Feb 20;10(2):e0117383. doi: 10.1371/journal.pone.0117383. eCollection 2015. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Composite outcome | The composite endpoint includes all-cause mortality, unplanned emergency visit (general practitioner or emergency outpatient clinic), and unplanned hospital admission for any reason. The investigators will calculate the proportion of the outcome in each arm. | 3 months | |
Secondary | All-cause mortality | Death from any cause. The proportion of the outcome will be calculated in each arm and compared between the arms. The investigators will compare subgroups of patients based on the cause of mortality. | 1, and 3 months | |
Secondary | Unplanned emergency visits | Emergency visit from any cause. The proportion of the outcome will be calculated in each arm and compared between the arms. The investigators will compare subgroups of patients based on the cause of unplanned emergency visits. | 1, and 3 months | |
Secondary | Unplanned hospital admission | Hospital admission from any cause. The proportion of the outcome will be calculated in each arm and compared between the arms. The investigators will compare subgroups of patients based on the cause of unplanned admission. | 1, and 3 months | |
Secondary | Quality of life using the 36-Item Short-Form Health Survey | Changes in quality of life measured with the 36-Item Short-Form Health Survey (SF-36) questionnaire compared to baseline. | 1, and 3 months +/- 7 days | |
Secondary | Quality of life using the EuroQol five-dimensions - 5 levels questionnare | Changes in quality of life measured with the EuroQol five-dimensions - 5 levels (EQ-5D-5L) questionnaire compared to baseline. | 1, and 3 months +/- 7 days | |
Secondary | Gait speed | Changes in gait speed compared to baseline. Gait speed will be evaluated on a 4-meter flat walking path. | 1, and 3 months +/- 7 days | |
Secondary | Six-Minute Walk Test (6MWT) | Changes in Six-Minute Walk Test (6MWT) compared to baseline. | 1, and 3 months +/- 7 days | |
Secondary | Handgrip strength | Changes in handgrip strength compared to baseline. | 1, and 3 months +/- 7 days | |
Secondary | Normalization of the haemoglobin level | The percentage of participants with Hb levels of =12 g/dL in women and =13 g/d, compared to baseline. | 1, and 3 months +/- 7 days | |
Secondary | Change in Hb level | Absolute change from baseline to follow-up in Hb level. | 1, and 3 months +/- 7 days | |
Secondary | Change in haematocrit | Absolute change from baseline to follow-up in haematocrit. | 1, and 3 months +/- 7 days | |
Secondary | Change in serum iron level | Absolute change from baseline to follow-up in serum iron level. | 1, and 3 months +/- 7 days | |
Secondary | Change in serum transferrin level | Absolute change from baseline to follow-up in serum transferrin level. | 1, and 3 months +/- 7 days | |
Secondary | Change in transferrin saturation | Absolute change from baseline to follow-up in transferrin saturation. | 1, and 3 months +/- 7 days | |
Secondary | Change in soluble transferrin receptor concentration | Absolute change from baseline to follow-up in soluble transferrin receptor (sTfR) concentration. | 1, and 3 months +/- 7 days | |
Secondary | Change in ferritin level | Absolute change from baseline to follow-up in ferritin level. | 1, and 3 months +/- 7 days | |
Secondary | Change in the number of reticulocytes | Absolute change from baseline to follow-up in the number of reticulocytes. | 1, and 3 months +/- 7 days | |
Secondary | Change in the number of erythrocytes | Absolute change from baseline to follow-up in the number of erythrocytes. | 1, and 3 months +/- 7 days | |
Secondary | Change in the total iron-binding capacity | Absolute change from baseline to follow-up in the total iron-binding capacity (TIBC). | 1, and 3 months +/- 7 days | |
Secondary | Change in erythropoietin level | Absolute change from baseline to follow-up in erythropoietin level. | 1, and 3 months +/- 7 days | |
Secondary | Change in C-reactive protein level | Absolute change from baseline to follow-up in the C-reactive protein level. | 1, and 3 months +/- 7 days | |
Secondary | Change in hepcidin level | Absolute change from baseline to follow-up in hepcidin level. | 1, and 3 months +/- 7 days | |
Secondary | Change in phosphate level | Absolute change from baseline to follow-up in phosphate level. | 1, and 3 months +/- 7 days | |
Secondary | Discontinuation of the treatment due to adverse events | The percentage of discontinuation in the two arms. | 1, and 3 months +/- 7 days | |
Secondary | Cost-effectiveness | The incremental cost-effectiveness ratio (ICER): incremental costs divided by incremental effectiveness . | 1, and 3 months +/- 7 days |
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