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

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.

Study Overview

• Status: Completed
• Conditions: Anemic, Critically Ill Patients
• Intervention / Treatment: Drug: Ferrous Sulfate; Drug: Placebo Oral Tablet

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.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: Ferrous Sulfate; Iron group
PLACEBO_COMPARATOR: 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.	Drug: Placebo Oral Tablet; Placebo group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hematocrit	Day 7, Day 14, Day 21, Day 28
Serum Iron Concentration	Day 7, Day 14, Day 21, Day 28
Serum Ferritin Concentration	Day 7, Day 14, Day 21, Day 28
Erythrocyte Zinc Protoporphyrin Concentration	Day 7, Day 14, Day 21, Day 28

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Investigators: Principal Investigator: Philip S Barie, MD, MBA, Weill Medical College of Cornell University

Publications and helpful links

General Publications

• Pieracci FM, Henderson P, Rodney JR, Holena DN, Genisca A, Ip I, Benkert S, Hydo LJ, Eachempati SR, Shou J, Barie PS. Randomized, double-blind, placebo-controlled trial of effects of enteral iron supplementation on anemia and risk of infection during surgical critical illness. Surg Infect (Larchmt). 2009 Feb;10(1):9-19. doi: 10.1089/sur.2008.043.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2006
• Primary Completion (ACTUAL): December 1, 2007
• Study Completion (ACTUAL): January 1, 2008

Study Registration Dates

• First Submitted: March 20, 2007
• First Submitted That Met QC Criteria: March 20, 2007
• First Posted (ESTIMATE): March 21, 2007

Study Record Updates

• Last Update Posted (ACTUAL): July 18, 2019
• Last Update Submitted That Met QC Criteria: July 8, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: anemia; infection; critical illness; iron
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: 052007738