Intravenous Ferric Carboxymaltose Versus Oral Ferrous Sulfate Replacement in Anaemia Due to Acute Nonvariceal Gastrointestinal Bleeding (FIERCE): Protocol of a Multicentre Randomised Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 570
- 试验地点
- 1
- 主要终点
- Composite outcome
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age ≥ 65 years;
- •endoscopically proven acute nonvariceal GIB source;
- •48 hours after the endoscopic diagnosis and/or treatment;
- •hemodynamically stable;
- •the discharge of the patient is planned;
- •hemoglobin level <10 g/dl on the day of randomisation;
- •24 hours after the last transfusion and no need for further transfusion;
- •signed informed consent.
排除标准
- •known hypersensitivity to iron products (mild side effects excluded);
- •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;
- •pregnancy or breast feeding;
- •diagnosis of iron malabsorption (at discretion of the attending clinician; e.g., severe inflammatory bowel disease, active celiac disease);
- •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);
- •active malignancies;
- •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;
- •gastrointestinal tract malignancies with high risk of gastrointestinal bleeding;
- •high risk of poor compliance or no fixed abode;
- •myelo- or lymphoproliferative diseases;
- •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);
- •primary coagulation disorders (e.g. Glanzmann thrombasthenia, Von Willebrand disease, Haemophylia A, Haemophylia B);
- •the patient will be transferred to another institute after discharge (e.g. hospital, senior care center);
- •Eastern Cooperative Oncology Group (ECOG) Performance Status >2.
研究组 & 干预措施
Oral iron supplementation
Patients randomized to receive oral ferrous sulfate, ca. 200-300 mg every day for 3 months.
干预措施: Oral iron supplementation (Drug)
Intravenous iron supplementation
Patients randomized to receive one dose of 1000 mg intravenous ferric carboxymaltose.
干预措施: Intravenous iron supplementation (Drug)
结局指标
主要结局
Composite outcome
时间窗: 3 months
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.
次要结局
- Six-Minute Walk Test (6MWT)(1, and 3 months +/- 7 days)
- Change in erythropoietin level(1, and 3 months +/- 7 days)
- Unplanned hospital admission(1, and 3 months)
- Quality of life using the 36-Item Short-Form Health Survey(1, and 3 months +/- 7 days)
- Change in Hb level(1, and 3 months +/- 7 days)
- Change in serum transferrin level(1, and 3 months +/- 7 days)
- Change in the number of reticulocytes(1, and 3 months +/- 7 days)
- Change in the number of erythrocytes(1, and 3 months +/- 7 days)
- Change in C-reactive protein level(1, and 3 months +/- 7 days)
- All-cause mortality(1, and 3 months)
- Gait speed(1, and 3 months +/- 7 days)
- Quality of life using the EuroQol five-dimensions - 5 levels questionnare(1, and 3 months +/- 7 days)
- Change in haematocrit(1, and 3 months +/- 7 days)
- Change in transferrin saturation(1, and 3 months +/- 7 days)
- Change in ferritin level(1, and 3 months +/- 7 days)
- Change in the total iron-binding capacity(1, and 3 months +/- 7 days)
- Unplanned emergency visits(1, and 3 months)
- Change in serum iron level(1, and 3 months +/- 7 days)
- Change in phosphate level(1, and 3 months +/- 7 days)
- Handgrip strength(1, and 3 months +/- 7 days)
- Change in soluble transferrin receptor concentration(1, and 3 months +/- 7 days)
- Change in hepcidin level(1, and 3 months +/- 7 days)
- Cost-effectiveness(1, and 3 months +/- 7 days)
- Normalization of the haemoglobin level(1, and 3 months +/- 7 days)
- Discontinuation of the treatment due to adverse events(1, and 3 months +/- 7 days)
研究者
dr Erőss Bálint
Principal Investigator, Director of the Centre for Translational Medicine at University of Pécs
University of Pecs