Back to resultsIron Supplementation in Upper Non-variceal Gastrointestinal Bleeding (FIERCE)
Primary Purpose
GastroIntestinal Bleeding, Anemia
Status
Not yet recruiting
Phase
Phase 4
Locations
Hungary
Study Type
Interventional
Intervention
Oral iron supplementation
Intravenous iron supplementation
Sponsored by
About this trial
This is an interventional treatment trial for GastroIntestinal Bleeding focused on measuring non-variceal upper gastrointersinal bleeding, iron supplementation, intravenous iron
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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, 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).
Sites / Locations
- Institute for Translational Medicine, University of Pécs
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Oral iron supplementation
Intravenous iron supplementation
Arm Description
Patients randomized to receive oral ferrous sulfate, ca. 200-300 mg every day for 3 months.
Patients randomized to receive one dose of 1000 mg intravenous ferric carboxymaltose.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
Gait speed
Changes in gait speed compared to baseline. Gait speed will be evaluated on a 4-meter flat walking path.
Six-Minute Walk Test (6MWT)
Changes in Six-Minute Walk Test (6MWT) compared to baseline.
Handgrip strength
Changes in handgrip strength compared to baseline.
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.
Change in Hb level
Absolute change from baseline to follow-up in Hb level.
Change in haematocrit
Absolute change from baseline to follow-up in haematocrit.
Change in serum iron level
Absolute change from baseline to follow-up in serum iron level.
Change in serum transferrin level
Absolute change from baseline to follow-up in serum transferrin level.
Change in transferrin saturation
Absolute change from baseline to follow-up in transferrin saturation.
Change in soluble transferrin receptor concentration
Absolute change from baseline to follow-up in soluble transferrin receptor (sTfR) concentration.
Change in ferritin level
Absolute change from baseline to follow-up in ferritin level.
Change in the number of reticulocytes
Absolute change from baseline to follow-up in the number of reticulocytes.
Change in the number of erythrocytes
Absolute change from baseline to follow-up in the number of erythrocytes.
Change in the total iron-binding capacity
Absolute change from baseline to follow-up in the total iron-binding capacity (TIBC).
Change in erythropoietin level
Absolute change from baseline to follow-up in erythropoietin level.
Change in C-reactive protein level
Absolute change from baseline to follow-up in the C-reactive protein level.
Change in hepcidin level
Absolute change from baseline to follow-up in hepcidin level.
Change in phosphate level
Absolute change from baseline to follow-up in phosphate level.
Discontinuation of the treatment due to adverse events
The percentage of discontinuation in the two arms.
Cost-effectiveness
The incremental cost-effectiveness ratio (ICER): incremental costs divided by incremental effectiveness .
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05060731
Brief Title
Iron Supplementation in Upper Non-variceal Gastrointestinal Bleeding
Acronym
FIERCE
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
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 1, 2023 (Anticipated)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
February 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pecs
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
GastroIntestinal Bleeding, Anemia
Keywords
non-variceal upper gastrointersinal bleeding, iron supplementation, intravenous iron
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
The investigators plan to recruit 285 patients on each arm.
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
570 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Oral iron supplementation
Arm Type
Active Comparator
Arm Description
Patients randomized to receive oral ferrous sulfate, ca. 200-300 mg every day for 3 months.
Arm Title
Intravenous iron supplementation
Arm Type
Active Comparator
Arm Description
Patients randomized to receive one dose of 1000 mg intravenous ferric carboxymaltose.
Intervention Type
Drug
Intervention Name(s)
Oral iron supplementation
Intervention Description
Ca. 200-300 mg of ferrous sulfate will be administered orally every day for 3 months.
Intervention Type
Drug
Intervention Name(s)
Intravenous iron supplementation
Intervention Description
One dose of intravenous 1000 mg ferric carboxymaltose will be administered on the day of randomization.
Primary Outcome Measure Information:
Title
Composite outcome
Description
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.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
All-cause mortality
Description
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.
Time Frame
1, and 3 months
Title
Unplanned emergency visits
Description
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.
Time Frame
1, and 3 months
Title
Unplanned hospital admission
Description
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.
Time Frame
1, and 3 months
Title
Quality of life using the 36-Item Short-Form Health Survey
Description
Changes in quality of life measured with the 36-Item Short-Form Health Survey (SF-36) questionnaire compared to baseline.
Time Frame
1, and 3 months +/- 7 days
Title
Quality of life using the EuroQol five-dimensions - 5 levels questionnare
Description
Changes in quality of life measured with the EuroQol five-dimensions - 5 levels (EQ-5D-5L) questionnaire compared to baseline.
Time Frame
1, and 3 months +/- 7 days
Title
Gait speed
Description
Changes in gait speed compared to baseline. Gait speed will be evaluated on a 4-meter flat walking path.
Time Frame
1, and 3 months +/- 7 days
Title
Six-Minute Walk Test (6MWT)
Description
Changes in Six-Minute Walk Test (6MWT) compared to baseline.
Time Frame
1, and 3 months +/- 7 days
Title
Handgrip strength
Description
Changes in handgrip strength compared to baseline.
Time Frame
1, and 3 months +/- 7 days
Title
Normalization of the haemoglobin level
Description
The percentage of participants with Hb levels of ≥12 g/dL in women and ≥13 g/d, compared to baseline.
Time Frame
1, and 3 months +/- 7 days
Title
Change in Hb level
Description
Absolute change from baseline to follow-up in Hb level.
Time Frame
1, and 3 months +/- 7 days
Title
Change in haematocrit
Description
Absolute change from baseline to follow-up in haematocrit.
Time Frame
1, and 3 months +/- 7 days
Title
Change in serum iron level
Description
Absolute change from baseline to follow-up in serum iron level.
Time Frame
1, and 3 months +/- 7 days
Title
Change in serum transferrin level
Description
Absolute change from baseline to follow-up in serum transferrin level.
Time Frame
1, and 3 months +/- 7 days
Title
Change in transferrin saturation
Description
Absolute change from baseline to follow-up in transferrin saturation.
Time Frame
1, and 3 months +/- 7 days
Title
Change in soluble transferrin receptor concentration
Description
Absolute change from baseline to follow-up in soluble transferrin receptor (sTfR) concentration.
Time Frame
1, and 3 months +/- 7 days
Title
Change in ferritin level
Description
Absolute change from baseline to follow-up in ferritin level.
Time Frame
1, and 3 months +/- 7 days
Title
Change in the number of reticulocytes
Description
Absolute change from baseline to follow-up in the number of reticulocytes.
Time Frame
1, and 3 months +/- 7 days
Title
Change in the number of erythrocytes
Description
Absolute change from baseline to follow-up in the number of erythrocytes.
Time Frame
1, and 3 months +/- 7 days
Title
Change in the total iron-binding capacity
Description
Absolute change from baseline to follow-up in the total iron-binding capacity (TIBC).
Time Frame
1, and 3 months +/- 7 days
Title
Change in erythropoietin level
Description
Absolute change from baseline to follow-up in erythropoietin level.
Time Frame
1, and 3 months +/- 7 days
Title
Change in C-reactive protein level
Description
Absolute change from baseline to follow-up in the C-reactive protein level.
Time Frame
1, and 3 months +/- 7 days
Title
Change in hepcidin level
Description
Absolute change from baseline to follow-up in hepcidin level.
Time Frame
1, and 3 months +/- 7 days
Title
Change in phosphate level
Description
Absolute change from baseline to follow-up in phosphate level.
Time Frame
1, and 3 months +/- 7 days
Title
Discontinuation of the treatment due to adverse events
Description
The percentage of discontinuation in the two arms.
Time Frame
1, and 3 months +/- 7 days
Title
Cost-effectiveness
Description
The incremental cost-effectiveness ratio (ICER): incremental costs divided by incremental effectiveness .
Time Frame
1, and 3 months +/- 7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bálint Erőss, MD, PhD
Phone
+3630/887-4028
Email
eross.balint@pte.hu
First Name & Middle Initial & Last Name or Official Title & Degree
Péter Hegyi, MD, PhD, DSc, MAE
Phone
+3670/375-1031
Email
p.hegyi@tm-centre.org
Facility Information:
Facility Name
Institute for Translational Medicine, University of Pécs
City
Pécs
ZIP/Postal Code
7624
Country
Hungary
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
29487213
Citation
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Results Reference
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18498676
Citation
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.
Results Reference
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Results Reference
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Citation
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.
Results Reference
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PubMed Identifier
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Citation
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.
Results Reference
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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.
Results Reference
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Links:
URL
https://tm-centre.org/en/research/clinical-trials/
Description
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Iron Supplementation in Upper Non-variceal Gastrointestinal Bleeding
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