Iron Supplementation in Upper Non-variceal Gastrointestinal Bleeding

NCT05060731 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 46395-5/2021/EÜIG
• Study Type: interventional
• Target: 570
• Locations: 1 country
• Sites: 1

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.

Conditions

GastroIntestinal Bleeding; Anemia

Keywords

non-variceal upper gastrointersinal bleeding; iron supplementation; intravenous iron

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (25)

• All-cause mortality

  1, and 3 months

• Unplanned emergency visits

  1, and 3 months

• Unplanned hospital admission

  1, and 3 months

• Quality of life using the 36-Item Short-Form Health Survey

  1, and 3 months +/- 7 days

• Quality of life using the EuroQol five-dimensions - 5 levels questionnare

  1, and 3 months +/- 7 days

Study Arms (2)

Oral iron supplementation

ACTIVE COMPARATOR

Patients randomized to receive oral ferrous sulfate, ca. 200-300 mg every day for 3 months.

Drug: Oral iron supplementation

Intravenous iron supplementation

ACTIVE COMPARATOR

Patients randomized to receive one dose of 1000 mg intravenous ferric carboxymaltose.

Drug: Intravenous iron supplementation

Interventions

Oral iron supplementation DRUG

Ca. 200-300 mg of ferrous sulfate will be administered orally every day for 3 months.

Oral iron supplementation

Intravenous iron supplementation DRUG

One dose of intravenous 1000 mg ferric carboxymaltose will be administered on the day of randomization.

Intravenous iron supplementation

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• age ≥ 65 years;
• endoscopically proven acute nonvariceal GIB source;
• 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;
• hours after the last transfusion and no need for further transfusion;
• signed informed consent.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pecs: lead

Study Sites (1)

Institute for Translational Medicine, University of Pécs

Pécs, 7624, Hungary

Location

Related Publications (8)

• McNutt MK, Bradford M, Drazen JM, Hanson B, Howard B, Jamieson KH, Kiermer V, Marcus E, Pope BK, Schekman R, Swaminathan S, Stang PJ, Verma IM. Transparency in authors' contributions and responsibilities to promote integrity in scientific publication. Proc Natl Acad Sci U S A. 2018 Mar 13;115(11):2557-2560. doi: 10.1073/pnas.1715374115. Epub 2018 Feb 27.

  PMID: 29487213 BACKGROUND

• McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005. Public Health Nutr. 2009 Apr;12(4):444-54. doi: 10.1017/S1368980008002401. Epub 2008 May 23.

  PMID: 18498676 BACKGROUND

• 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.

  PMID: 31197861 BACKGROUND

• 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.

  PMID: 24251969 BACKGROUND

• 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.

  PMID: 25700159 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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-2022-063554.

  PMID: 36918236 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Gastrointestinal Hemorrhage; Anemia

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Bálint Erőss, MD, PhD

CONTACT

+3630/887-4028; eross.balint@pte.hu

Péter Hegyi, MD, PhD, DSc, MAE

CONTACT

+3670/375-1031; p.hegyi@tm-centre.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Director of the Centre for Translational Medicine at University of Pécs

Model Details: The investigators plan to recruit 285 patients on each arm.

Study Record Dates

• First Submitted: September 17, 2021
• First Posted: September 29, 2021
• Study Start: September 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: March 30, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)