IV Iron for the Anemia of Traumatic Critical Illness (IATCI)

A Multicenter, Randomized, Double-blind Comparison of Intravenous Iron Supplementation to Placebo for the Treatment of Anemia of Traumatic Critical Illness

The purpose of this clinical trial is to determine whether intravenous iron supplementation of anemic, critically ill trauma patients improves anemia and reduces the need for a red blood cell transfusion.

Study Overview

• Status: Completed
• Conditions: Trauma; ICU Anemia
• Intervention / Treatment: Drug: Placebo; Drug: Iron sucrose

Detailed Description

Nearly all trauma patients admitted to an intensive care unit (ICU) are anemic (low red blood cell counts). Anemia is an independent risk factor for poor outcomes, including infection, impaired wound healing, and death. Current therapies for ICU anemia are unsatisfactory: Red blood cell (RBC) transfusion is associated with an increased risk of immune suppression, infection, and organ failure. Furthermore, use of both hemoglobin replacement products and erythropoietin are limited by expense as well as unfavorable side effect profiles.

One principal cause of anemia in trauma ICU patients involves disturbances in iron metabolism. Iron is necessary to make RBCs, and a lack of iron delivered to the bone marrow results in anemia. Trauma causes diversion of iron from the bone marrow into storage, where it cannot participate in the generation of RBCs. This diversion of iron is caused by inflammatory proteins released as a result of tissue injury.

Previous work by the principal investigator among ICU patients suggested a benefit to oral iron supplementation administered in dosages similar to those used in a standard multivitamin. However, many patients were not able to tolerate oral medications, and this study was not specific to trauma patients. Additional research has suggested that intravenous iron supplementation is effective in treating anemic patients with other inflammatory conditions, such as cancer and inflammatory bowel disease. However, the benefit of intravenous iron supplementation has never been tested among anemic ICU patients, including trauma patients.

The current clinical trial will evaluate the risk/benefit profile of intravenous iron supplementation among anemic trauma ICU patients. The study will take place over several academic trauma centers with a long history of participation in translational research.

Anemia remains a devastating complication of trauma. Current treatment options are limited. Intravenous iron supplementation represents a targeted, cost-effective solution to this pervasive problem, the efficacy of which remains undefined.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48103
      • University of Michigan Health Systems
  • New York
    • New York, New York, United States, 10065
      • NewYork Presbyterian Medical Center/Weill Cornell Medical College
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15201
      • University of Pittsburgh Medical Center
  • Washington
    • Seattle, Washington, United States, 98102
      • Harborview Medical Center/University of Washington

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:

• ICU admission for trauma
• Adults (age ≥ 18 years)
• Anemia (hemoglobin < 12 g/dL)
• ≤ 72 hours from ICU admission
• Expected ICU length of stay ≥ 7 days

Exclusion Criteria:

• Active hemorrhage requiring RBC transfusion
• Iron overload (serum ferritin concentration ≥ 1,000 ng/mL) or any condition associated with iron overload (e.g., hemochromatosis, aceruloplasminemia
• Chronic inflammatory conditions (e.g., systemic lupus erythematosis, rheumatoid arthritis, ankylosing spondilitis)
• Pre-existing hematologic disorders (e.g., thalassemia, sickle cell disease, hemophilia, von Willibrand's disease, myeloproliferative disease)
• Macrocytic anemia (mean corpuscular volume ≥ 100 fL)
• Current use of immunosuppressive agents including corticosteroids (e.g., dexamethasone, hydrocortisone, methylprednisolone, prednisone, exclusive of inhaled corticosteroids), calcinurin inhibitors (e.g., cyclosporine, tacrolimus), antimetabolites (e.g., azathioprine), or biologics (e.g., OKT3, thymoglobulin)
• Use of recombinant human erythropoietin formulation within the prev 30 days
• Pregnancy or lactation
• Prohibition of RBC transfusion
• Stay of ≥ 48 hours duration in the ICU of a transferring hospital
• History of intolerance or hypersensitivity to either enteral or intravenous iron
• Moribund state in which death is imminent
• Enrollment in any other clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Iron sucrose; 100 mg IV TIW	Drug: Iron sucrose; 100 mg IV TIW; Other Names: Fe sucrose
Placebo Comparator: Placebo; Pacebo - Normal Saline	Drug: Placebo; Other Names: control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RBC Transfusion	The number of participants who underwent RBC transfusion.	42 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Iron-deficient Erythropoeisis (IDE)	An elevated eZPP is diagnostic of Iron-deficient erythropoiesis (IDE) and reflects the bone marrow iron supply regardless of total body iron.	14 Days
Infection	The number of participants with at least one infection. Specific infections analyzed included VAP (Ventilator-Associated Pneumonia), bacteremia, and urinary tract infection (UTI).	28 Days
The Number of Participants Who Died		28 Days

Collaborators and Investigators

• Sponsor: Denver Health and Hospital Authority
• Collaborators: National Trauma Research Institute
• Investigators: Principal Investigator: Fredric M Pieracci, MD, MPH, Denver Health Medical Center, University of Colorado Health Science Center

Publications and helpful links

General Publications

• Pieracci FM, Stovall RT, Jaouen B, Rodil M, Cappa A, Burlew CC, Holena DN, Maier R, Berry S, Jurkovich J, Moore EE. A multicenter, randomized clinical trial of IV iron supplementation for anemia of traumatic critical illness*. Crit Care Med. 2014 Sep;42(9):2048-57. doi: 10.1097/CCM.0000000000000408.

Helpful Links

• National Trauma Institute

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: August 11, 2010
• First Submitted That Met QC Criteria: August 11, 2010
• First Posted (Estimate): August 12, 2010

Study Record Updates

• Last Update Posted (Actual): February 5, 2018
• Last Update Submitted That Met QC Criteria: January 10, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Anemia; Iron; Trauma; Erythropoeisis
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Hematologic Diseases; Critical Illness; Anemia; Hematinics; Ferric Oxide, Saccharated
• Other Study ID Numbers: 10-0705

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO