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Efficacy of Enteral Iron Supplementation in Critical Illness

A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of the Effects of Enteral Iron Supplementation on Anemia and Risk of Infection in Critical Illness

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00450177
Enrollment
200
Registered
2007-03-21
Start date
2006-01-31
Completion date
2008-01-31
Last updated
2019-07-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anemic, Critically Ill Patients

Keywords

iron, critical illness, anemia, infection

Brief summary

The purpose of this study is to investigate the efficacy of enteral iron supplementation for improving anemia, decreasing the risk of blood transfusion, and decreasing mortality in patients who are hospitalized in the intensive care unit. This study will also address any relationship between enteral iron supplementation and risk of infection.

Detailed description

Critical illness is characterized by the anemia of inflammation, which is partially caused by sequestration of iron from bone marrow sites of erythropoiesis into storage within the reticuloendothelial system as ferritin. Also the majority of critically ill patients are hypoferremia, the efficacy of iron supplementation remains unknown. Furthermore, several retrospective studies have found an association between iron overload and infection. However, the relative risk/benefit profile of enteral iron supplementation with respect to infection has not been studied. The purpose of this study is to evaluate the efficacy of enteral iron supplementation in critically ill patients. The hypothesis is that enteral iron supplementation will result in both an improved hematocrit and a decreased need for blood transfusion, without increasing the risk of infection.

Interventions

DRUGFerrous Sulfate

Iron group

DRUGPlacebo Oral Tablet

Placebo group

Sponsors

Weill Medical College of Cornell University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Age \> 18 years * Anemia (Hemoglobin \< 13.0 g/dL) * ≤ 72 hours from hospital admission * Current tolerance of enteral medications * Expected ICU LOS \> 5 days

Exclusion criteria

* Active bleeding * Chronic inflammatory disease * End-stage renal disease * Hematologic disorders * Macrocytic anemia * Current use of erythropoietin * Pregnancy * Prohibition of RBC transfusions * Moribund state in which death is imminent * Enrollment in another clinical trial

Design outcomes

Primary

MeasureTime frame
Erythrocyte Zinc Protoporphyrin ConcentrationDay 7, Day 14, Day 21, Day 28
HematocritDay 7, Day 14, Day 21, Day 28
Serum Iron ConcentrationDay 7, Day 14, Day 21, Day 28
Serum Ferritin ConcentrationDay 7, Day 14, Day 21, Day 28

Secondary

MeasureTime frame
Hospital Mortality, as Measured by Number of Subject Deaths While Admitted to HospitalThroughout hospital stay up to 6 weeks
Number of Subjects That Received at Least One RBC Transfusion During Admission to the HospitalThroughout hospital stay up to 6 weeks
Average Length of Stay in the HospitalThroughout hospital stay up to 6 weeks
Number of Subjects That Incurred at Least One Infection Throughout Hospital AdmissionThroughout hospital stay up to 6 weeks
Instance of Drug-related Constipation Throughout Hospital AdmissionThroughout hospital stay up to 6 weeks
Average Number of Days That Subjects Were Taking AntibioticsThroughout hospital stay up to 6 weeks

Countries

United States

Participant flow

Participants by arm

ArmCount
Iron Group
Ferrous sulfate 325 mg either by capsule or oral solution three times a day at 9 am, 1pm and 5 pm until hospital discharge or for 42 days, whichever occurs first. Ferrous Sulfate: Iron group
97
Placebo Group
Placebo capsule three times a day at 9 am, 1pm and 5 pm until hospital discharge or for 42 days, whichever occurs first. Placebo Oral Tablet: Placebo group
103
Total200

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyAdverse Event74
Overall StudyWithdrawal by Primary Team11
Overall StudyWithdrawal by Subject16

Baseline characteristics

CharacteristicIron GroupTotalPlacebo Group
Admission APACHE II15.9 units on a scale
STANDARD_DEVIATION 0.8
15.4 units on a scale
STANDARD_DEVIATION 0.8
14.9 units on a scale
STANDARD_DEVIATION 0.8
Admission to enrollment1.6 days
STANDARD_DEVIATION 0.1
1.7 days
STANDARD_DEVIATION 0.1
1.7 days
STANDARD_DEVIATION 0.1
Age, Continuous55.7 years
STANDARD_DEVIATION 1.9
57.0 years
STANDARD_DEVIATION 1.7
58.2 years
STANDARD_DEVIATION 1.7
Baseline EBL171 milliliters
STANDARD_DEVIATION 45
189 milliliters
STANDARD_DEVIATION 48
207 milliliters
STANDARD_DEVIATION 50
Baseline hematocrit32.0 % of RBC in total blood volume
STANDARD_DEVIATION 0.5
31.9 % of RBC in total blood volume
STANDARD_DEVIATION 0.4
31.9 % of RBC in total blood volume
STANDARD_DEVIATION 0.4
Baseline MCV88.7 femtoliters
STANDARD_DEVIATION 0.7
88.6 femtoliters
STANDARD_DEVIATION 0.8
88.6 femtoliters
STANDARD_DEVIATION 0.8
Baseline RBC transfusion135 milliliters
STANDARD_DEVIATION 58
222 milliliters
STANDARD_DEVIATION 85
303 milliliters
STANDARD_DEVIATION 110
Race and Ethnicity Not Collected—0 Participants—
Sex: Female, Male
Female
48 Participants103 Participants55 Participants
Sex: Female, Male
Male
49 Participants97 Participants48 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
7 / 974 / 103
serious
Total, serious adverse events
0 / 970 / 103

Outcome results

Primary

Erythrocyte Zinc Protoporphyrin Concentration

Time frame: Day 7, Day 14, Day 21, Day 28

ArmMeasureGroupValue (MEAN)Dispersion
Iron GroupErythrocyte Zinc Protoporphyrin ConcentrationDay 2884 micromol:mol hemeStandard Deviation 6
Iron GroupErythrocyte Zinc Protoporphyrin ConcentrationDay 1475 micromol:mol hemeStandard Deviation 6
Iron GroupErythrocyte Zinc Protoporphyrin ConcentrationDay 769 micromol:mol hemeStandard Deviation 4
Iron GroupErythrocyte Zinc Protoporphyrin ConcentrationDay 2186 micromol:mol hemeStandard Deviation 5
Placebo GroupErythrocyte Zinc Protoporphyrin ConcentrationDay 767 micromol:mol hemeStandard Deviation 5
Placebo GroupErythrocyte Zinc Protoporphyrin ConcentrationDay 2889 micromol:mol hemeStandard Deviation 5
Placebo GroupErythrocyte Zinc Protoporphyrin ConcentrationDay 2191 micromol:mol hemeStandard Deviation 6
Placebo GroupErythrocyte Zinc Protoporphyrin ConcentrationDay 1477 micromol:mol hemeStandard Deviation 5
Primary

Hematocrit

Time frame: Day 7, Day 14, Day 21, Day 28

ArmMeasureGroupValue (MEAN)Dispersion
Iron GroupHematocritDay 729.3 percentage of RBC in bloodStandard Deviation 0.5
Iron GroupHematocritDay 1428.6 percentage of RBC in bloodStandard Deviation 0.4
Iron GroupHematocritDay 2129.2 percentage of RBC in bloodStandard Deviation 0.4
Iron GroupHematocritDay 2827.8 percentage of RBC in bloodStandard Deviation 0.6
Placebo GroupHematocritDay 2828.1 percentage of RBC in bloodStandard Deviation 0.5
Placebo GroupHematocritDay 729.1 percentage of RBC in bloodStandard Deviation 0.5
Placebo GroupHematocritDay 2128.1 percentage of RBC in bloodStandard Deviation 0.6
Placebo GroupHematocritDay 1428.2 percentage of RBC in bloodStandard Deviation 0.5
Primary

Serum Ferritin Concentration

Time frame: Day 7, Day 14, Day 21, Day 28

ArmMeasureGroupValue (MEAN)Dispersion
Iron GroupSerum Ferritin ConcentrationDay 7280 ng/mLStandard Deviation 46
Iron GroupSerum Ferritin ConcentrationDay 14268 ng/mLStandard Deviation 51
Iron GroupSerum Ferritin ConcentrationDay 21251 ng/mLStandard Deviation 40
Iron GroupSerum Ferritin ConcentrationDay 28383 ng/mLStandard Deviation 54
Placebo GroupSerum Ferritin ConcentrationDay 28361 ng/mLStandard Deviation 76
Placebo GroupSerum Ferritin ConcentrationDay 7265 ng/mLStandard Deviation 73
Placebo GroupSerum Ferritin ConcentrationDay 21355 ng/mLStandard Deviation 83
Placebo GroupSerum Ferritin ConcentrationDay 14268 ng/mLStandard Deviation 80
Primary

Serum Iron Concentration

Time frame: Day 7, Day 14, Day 21, Day 28

ArmMeasureGroupValue (MEAN)Dispersion
Iron GroupSerum Iron ConcentrationDay 735 mcg/mLStandard Deviation 0.6
Iron GroupSerum Iron ConcentrationDay 1434 mcg/mLStandard Deviation 0.5
Iron GroupSerum Iron ConcentrationDay 2134 mcg/mLStandard Deviation 0.6
Iron GroupSerum Iron ConcentrationDay 2837 mcg/mLStandard Deviation 0.5
Placebo GroupSerum Iron ConcentrationDay 2836 mcg/mLStandard Deviation 0.7
Placebo GroupSerum Iron ConcentrationDay 737 mcg/mLStandard Deviation 0.7
Placebo GroupSerum Iron ConcentrationDay 2140 mcg/mLStandard Deviation 0.6
Placebo GroupSerum Iron ConcentrationDay 1434 mcg/mLStandard Deviation 0.7
Secondary

Average Length of Stay in the Hospital

Time frame: Throughout hospital stay up to 6 weeks

ArmMeasureValue (MEAN)Dispersion
Iron GroupAverage Length of Stay in the Hospital14 daysStandard Deviation 1
Placebo GroupAverage Length of Stay in the Hospital16 daysStandard Deviation 2
Secondary

Average Number of Days That Subjects Were Taking Antibiotics

Time frame: Throughout hospital stay up to 6 weeks

ArmMeasureValue (MEAN)Dispersion
Iron GroupAverage Number of Days That Subjects Were Taking Antibiotics14 daysStandard Deviation 2
Placebo GroupAverage Number of Days That Subjects Were Taking Antibiotics16 daysStandard Deviation 3
Secondary

Hospital Mortality, as Measured by Number of Subject Deaths While Admitted to Hospital

Time frame: Throughout hospital stay up to 6 weeks

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Iron GroupHospital Mortality, as Measured by Number of Subject Deaths While Admitted to Hospital9 Participants
Placebo GroupHospital Mortality, as Measured by Number of Subject Deaths While Admitted to Hospital10 Participants
Secondary

Instance of Drug-related Constipation Throughout Hospital Admission

Time frame: Throughout hospital stay up to 6 weeks

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Iron GroupInstance of Drug-related Constipation Throughout Hospital Admission12 Participants
Placebo GroupInstance of Drug-related Constipation Throughout Hospital Admission9 Participants
Secondary

Number of Subjects That Incurred at Least One Infection Throughout Hospital Admission

Time frame: Throughout hospital stay up to 6 weeks

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Iron GroupNumber of Subjects That Incurred at Least One Infection Throughout Hospital Admission45 Participants
Placebo GroupNumber of Subjects That Incurred at Least One Infection Throughout Hospital Admission48 Participants
Secondary

Number of Subjects That Received at Least One RBC Transfusion During Admission to the Hospital

Time frame: Throughout hospital stay up to 6 weeks

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Iron GroupNumber of Subjects That Received at Least One RBC Transfusion During Admission to the Hospital29 Participants
Placebo GroupNumber of Subjects That Received at Least One RBC Transfusion During Admission to the Hospital46 Participants
p-value: 0.03Chi-squared

Source: ClinicalTrials.gov · Data processed: Apr 3, 2026