Randomized Study Comparing Ferric Carboxymaltose to Iron Sucrose to Treat Fe Deficiency in the Surgically Critically Ill

NCT02009943 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: COMIRB 13-3151
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Critically ill surgical patients are observed to have a functional iron deficiency which contributes to anemia, iron-deficient erythropoiesis, and an increased red blood cell transfusion requirement. Previously, iron supplementation has been studied in this population with the administration of enteral ferrous sulfate and intravenous iron sucrose but without robust results in resolving serum and bone marrow iron debts. Ferric carboxymaltose (FCM) is novel iron-containing complex that allows for the administration of a large dose of iron over a short infusion period to allow for sustained delivery of iron to target tissues with minimal hypersensitivity reactions. While there has been reported increased efficacy and comparable safety of FCM when compared to iron sucrose in the outpatient setting, there is no data comparing these two medications in surgical critical illness. The aim of this pilot trial is to compare two novel dosing schemes of these medications for treatment of functional iron deficiency in surgical ICU patients. The investigators hypothesize that iron supplementation with FCM, as compared to both iron sucrose and placebo, is more effective and equally safe for replacing the serum iron debt.

Conditions

ICU Anemia; Functional Iron Deficiency

Keywords

critical illness; iron supplementation; functional iron deficiency; ICU anemia; red blood cell transfusion

Outcome Measures

Primary Outcomes (1)

• Reversal of the serum iron debt as measured by the transferrin saturation

  Because only a small fraction of total body iron is dissolved in blood, the TSAT is currently regarded as the most accurate indicator of iron substrate available for deposition in the bone marrow and eventual incorporation into erythrocytes. Data from outpatients indicate that TSAT is a more reliable predictor of hemoglobin response as compared to either serum iron concentration or serum ferritin concentration, with a target TSAT of 25-50% considered ideal for bone marrow iron delivery. In NCT01180894, TSAT began and remained \<16% despite iron supplementation with iron sucrose 100 mg IV thrice weekly. The target TSAT for this trial will be 25%-50%.

  One week

Secondary Outcomes (5)

• Bone marrow iron debt

  One week

• Serum ferritin concentration

  One week

• Hemoglobin

  28 days

• Red blood cell transfusion requirement

  28 days

• Nosocomial infections

  28 days

Study Arms (3)

Ferric carboxymaltose (FDA IND pending)

EXPERIMENTAL

15 mg/kg, up to 750 mg IV x 1 on the day of study enrollment.

Drug: Ferric carboxymaltose

Iron sucrose (FDA IND 109,877)

ACTIVE COMPARATOR

Iron sucrose 100 mg IV will be dosed daily using goal-direction up to a total of 700 mg over a 7-day period. Specifically, iron sucrose will be dosed daily if: 1. TSAT \< 25% 2. Serum iron concentration \< 150 ug/mL 3. Serum ferritin concentration \< 1,500 ng/mL

Drug: Iron sucrose

Control

NO INTERVENTION

No iron supplementation

Interventions

Ferric carboxymaltose DRUG

One time dosing

Also known as: Injectafer

Ferric carboxymaltose (FDA IND pending)

Iron sucrose DRUG

Goal-directed dosing

Iron sucrose (FDA IND 109,877)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Anemia (hemoglobin \< 12 g/dL).
• Functional iron deficiency:
• Serum iron concentration \< 40 ug/dL
• TSAT \< 25%
• Serum ferritin concentration \> 28 ng/mL
• \< 72 hours from ICU admission.
• Expected ICU length of stay ≥ 7 days.

You may not qualify if:

• Age \< 18 years.
• Active bleeding requiring pRBCs transfusion
• Iron overload (serum ferritin concentration ≥ 1,500 ng/mL). The serum ferritin concentration is an acute phase reactant that is increased during critical illness regardless of total body iron \[3\]. Substantial levels of hyperferritinemia (serum ferrinin concentration \> 1,000 ng/dL) were observed in both NCT00450177 and NCT01180894 without increased risk of infection and despite both low TSAT and IDE. For these reasons, we believe that relative hyperferritinemia (serum ferritin concentration 500 - 1,500 ng/dL) is neither harmful nor indicative of bone marrow iron availability.
• Infection, defined using US Centers for Disease Control and Prevention (CDC) guidelines, with the exception of ventilator-associated pneumonia (VAP), which is defined as clinical suspicion for pneumonia along with a lower respiratory tract culture with ≥ 105 colony forming units per mL.
• 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, or myeloproliferative disease).
• Macrocytic anemia (admission mean corpuscular volume ≥ 100 fL).
• Current or recent (within 30 days) use of immunosuppressive agents.
• Use of any recombinant human erythropoietin formulation within the previous 30 days.
• Pregnancy or lactation.
• Legal arrest or incarceration.
• Prohibition of pRBCs transfusion.
• Stay of ≥ 48 hours duration in the ICU of a transferring hospital.
• History of intolerance or hypersensitivity to iron.
• Moribund state in which death was imminent.

Sponsors & Collaborators

• Denver Health and Hospital Authority: lead

Study Sites (1)

Denver Health Medical Center

Denver, Colorado, 80204, United States

Location

MeSH Terms

Conditions

Critical Illness

Interventions

ferric carboxymaltose; Ferric Oxide, Saccharated

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ferric Compounds; Iron Compounds; Inorganic Chemicals; Glucaric Acid; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Study Officials

• Fredric M Pieracci, MD, MPH

  Denver Health and Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Surgery

Study Record Dates

• First Submitted: December 5, 2013
• First Posted: December 12, 2013
• Study Start: February 1, 2017
• Primary Completion: August 1, 2017
• Study Completion: September 1, 2017
• Last Updated: January 12, 2018

Record last verified: 2018-01

Locations

US (1)