Iron Supplementation in Upper Non-variceal Gastrointestinal Bleeding

Официальное название

Intravenous Ferric Carboxymaltose Versus Oral Ferrous Sulfate Replacement in Anaemia Due to Acute Nonvariceal Gastrointestinal Bleeding (FIERCE): Protocol of a Multicentre Randomised Controlled Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Oral iron supplementation
  Ca. 200-300 mg of ferrous sulfate will be administered orally every day for 3 months.
• Препарат Intravenous iron supplementation
  One dose of intravenous 1000 mg ferric carboxymaltose will be administered on the day of randomization.

Первичные конечные точки

• Composite outcome [Срок оценки: 3 months]

Вторичные конечные точки (12)

• All-cause mortality [Срок оценки: 1, and 3 months]
• Unplanned emergency visits [Срок оценки: 1, and 3 months]
• Unplanned hospital admission [Срок оценки: 1, and 3 months]
• Quality of life using the 36-Item Short-Form Health Survey [Срок оценки: 1, and 3 months +/- 7 days]
• Quality of life using the EuroQol five-dimensions - 5 levels questionnare [Срок оценки: 1, and 3 months +/- 7 days]
• Gait speed [Срок оценки: 1, and 3 months +/- 7 days]
• Six-Minute Walk Test (6MWT) [Срок оценки: 1, and 3 months +/- 7 days]
• Handgrip strength [Срок оценки: 1, and 3 months +/- 7 days]
• Normalization of the haemoglobin level [Срок оценки: 1, and 3 months +/- 7 days]
• Change in Hb level [Срок оценки: 1, and 3 months +/- 7 days]
• Change in haematocrit [Срок оценки: 1, and 3 months +/- 7 days]
• Change in serum iron level [Срок оценки: 1, and 3 months +/- 7 days]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Венгрия · 1 центр

• Institute for Translational Medicine, University of Pécs — Pécs

Публикации

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• Sultan P, Bampoe S, Shah R, Guo N, Estes J, Stave C, Goodnough LT, Halpern S, Butwick AJ. Oral vs intravenous iron therapy for postpartum anemia: a systematic review and meta-analysis. Am J Obstet Gynecol. 2019 Jul;221(1):19-29.e3. doi: 10.1016/j.ajog.2018.12.016. Epub 2018 Dec 19. PMID 30578747
• 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. PMID 33362380
• Teutsch B, Vancsa S, Farkas N, Szakacs Z, Vorhendi N, Boros E, Szabo I, Hagendorn R, Alizadeh H, Hegyi P, Eross B. Intravenous ferric carboxymaltose versus oral ferrous sulfate replacement in elderly patients after acute non-variceal gastrointestinal bleeding (FIERCE): protocol of a multicentre, open-label, randomised controlled trial. BMJ Open. 2023 Mar 14;13(3):e063554. doi: 10.1136/bmjopen-2022 PMID 36918236

Идентификаторы

NCT: NCT05060731 · 46395-5/2021/EÜIG

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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