Clinical trial NCT05060731: Iron Supplementation in Upper Non-variceal Gastrointestinal Bleeding
Official 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: GastroIntestinal Bleeding
Anemia
Keywords: non-variceal upper gastrointersinal bleeding
iron supplementation
intravenous iron
Lead sponsor: University of Pecs
Sponsor class: OTHER
First posted: 2021-09-29
Enrollment: 570
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The investigators plan to recruit 285 patients on each arm.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: In gastrointestinal bleeding (GIB) iron deficiency anemia (IDA) is a common complication, affecting more than 60% of the patients. There are two pillars of the treatment of acute GIB. First, the bleeding point needs identification and endoscopic treatment. Second, the resulting hypovolemia and anemia require fluid resuscitation, transfusion, and replacement of the lost iron. There are two simple ways to manage IDA after acute GIB. Patients either have intravenous (IV) iron infusions one to six times as part of their hospital treatment or receive three months of oral iron supplementation. There is a gap in current guidelines on which approach clinicians should choose.

Here the investigators plan a multicentric, two-arm, randomized controlled trial, to compare the efficacy of oral and intravenous iron supplementation in multimorbid patients with acute nonvariceal gastrointestinal bleeding. Patients will be randomly allocated in a 1:1 ratio to two groups. Group A will receive one dose of 1000 mg of IV ferric carboxymaltose on the day of randomization, while iron supplementation for group B will be performed with one ferrous sulfate tablet every day (ca. 200-300 mg) for three months. The primary outcome will be the composite outcome of all-cause mortality, unplanned emergency visit, and unplanned hospital readmission within six months after enrollment.

In the first phase, the investigators plan to recruit 15 patients on each arm to assess the proportion of the primary outcome in the two groups. In the second phase, a sample size calculation for the primary outcome will be performed based on the results of the first phase.

Eligibility criteria: 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.

Primary outcomes:
measure: Composite outcome
timeFrame: 3 months
Secondary outcomes:
measure: All-cause mortality
timeFrame: 1, and 3 months
measure: Unplanned emergency visits
timeFrame: 1, and 3 months
measure: Unplanned hospital admission
timeFrame: 1, and 3 months
measure: Quality of life using the 36-Item Short-Form Health Survey
timeFrame: 1, and 3 months +/- 7 days
measure: Quality of life using the EuroQol five-dimensions - 5 levels questionnare
timeFrame: 1, and 3 months +/- 7 days
measure: Gait speed
timeFrame: 1, and 3 months +/- 7 days
measure: Six-Minute Walk Test (6MWT)
timeFrame: 1, and 3 months +/- 7 days
measure: Handgrip strength
timeFrame: 1, and 3 months +/- 7 days
measure: Normalization of the haemoglobin level
timeFrame: 1, and 3 months +/- 7 days
measure: Change in Hb level
timeFrame: 1, and 3 months +/- 7 days
measure: Change in haematocrit
timeFrame: 1, and 3 months +/- 7 days
measure: Change in serum iron level
timeFrame: 1, and 3 months +/- 7 days
measure: Change in serum transferrin level
timeFrame: 1, and 3 months +/- 7 days
measure: Change in transferrin saturation
timeFrame: 1, and 3 months +/- 7 days
measure: Change in soluble transferrin receptor concentration
timeFrame: 1, and 3 months +/- 7 days
measure: Change in ferritin level
timeFrame: 1, and 3 months +/- 7 days
measure: Change in the number of reticulocytes
timeFrame: 1, and 3 months +/- 7 days
measure: Change in the number of erythrocytes
timeFrame: 1, and 3 months +/- 7 days
measure: Change in the total iron-binding capacity
timeFrame: 1, and 3 months +/- 7 days
measure: Change in erythropoietin level
timeFrame: 1, and 3 months +/- 7 days
measure: Change in C-reactive protein level
timeFrame: 1, and 3 months +/- 7 days
measure: Change in hepcidin level
timeFrame: 1, and 3 months +/- 7 days
measure: Change in phosphate level
timeFrame: 1, and 3 months +/- 7 days
measure: Discontinuation of the treatment due to adverse events
timeFrame: 1, and 3 months +/- 7 days
measure: Cost-effectiveness
timeFrame: 1, and 3 months +/- 7 days
Other outcomes:
Locations:
city: Pécs
country: Hungary
facility: Institute for Translational Medicine, University of Pécs
Study officials:
References:
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