RCT of Goal-directed Iron Supplementation of Anemic, Critically Ill Trauma Patients, With and Without Oxandrolone

NCT02047552 | Withdrawn Phase 2 DMC

• 1 other identifier: 14-0167
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this trial is to determine if the combination of goal directed iron supplementation and hepcidin mitigation can safely eliminate both the serum and bone marrow iron debt of anemic, critically ill trauma patients with functional iron deficiency.

Conditions

Functional Iron Deficiency; Trauma; Anemia

Keywords

trauma; iron; anemia; red blood cell transfusion

Outcome Measures

Primary Outcomes (1)

• Serum iron debt (as measured by the transferrin saturation)

  The transferrin saturation will be measured at baseline and daily thereafter for one week

  One week

Secondary Outcomes (9)

• Bone marrow iron debt (as measured by the zinc protoporphyrin)

  one week

• Serum ferritin concentration

  one week

• serum hepcidin concentration

  one week

• Liver function tests

  one week

• Erythropoeitin concentration

  one week

Study Arms (4)

Iron sucrose

ACTIVE COMPARATOR

Iron sucrose 100 mg IV will be dosed daily for up to seven days if, on morning laboratory analysis, (1) TSAT \< 25%, (2) Serum iron concentration \< 150 ug/mL, and (3) Serum ferritin concentration \< 1,500 ng/mL. Thus, the maximum possible cumulative dose of iron sucrose over the one-week dosing period will be 700 mg.

Drug: Iron sucrose; Drug: Oxandrolone placebo

Oxandrolone

ACTIVE COMPARATOR

Oxandrolone 10 mg PO q12 hours will be dosed for seven days.

Drug: Oxandrolone; Drug: IV iron placebo

Iron sucrose + oxandrolone

EXPERIMENTAL

Combination goal-directed iron sucrose (as described in the iron sucrose only arm) and oxandrolone (as described in the oxandrolone only arm) for seven days.

Drug: Iron sucrose; Drug: Oxandrolone

IV iron placebo and Oxandrolone placebo

PLACEBO COMPARATOR

100 mL normal saline in place of iron and similar color and size sugar pill for Oxandrolone placebo

Drug: IV iron placebo; Drug: Oxandrolone placebo

Interventions

Iron sucrose DRUG

Iron sucrose 100 mg IV will be dosed daily for up to seven days if, on morning laboratory analysis, (1) TSAT \< 25%, (2) Serum iron concentration \< 150 ug/mL, and (3) Serum ferritin concentration \< 1,500 ng/mL. Thus, the maximum possible cumulative dose of iron sucrose over the one-week dosing period will be 700 mg.

Also known as: Fe

Iron sucrose; Iron sucrose + oxandrolone

Oxandrolone DRUG

10 mg PO Q12 hours for seven days

Also known as: Steroid

Iron sucrose + oxandrolone; Oxandrolone

IV iron placebo DRUG

100 mL normal saline

Also known as: Fe placebo

IV iron placebo and Oxandrolone placebo; Oxandrolone

Oxandrolone placebo DRUG

similar color and size sugar pill

Also known as: Steroid placebo

IV iron placebo and Oxandrolone placebo; Iron sucrose

Eligibility Criteria

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

You may qualify if:

• Informed consent from patient or patient representative.
• Trauma patient
• 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. Substantial levels of hyperferritinemia (serum ferritin 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 spondylitis).
• Pre-existing hematologic disorders (e.g., thalassemia, sickle cell disease, hemophilia, von Willibrand's disease, or myeloproliferative disease).
• Pre-existing hepatic dysfunction (cirrhosis, non-alcoholic steatohepatitis, hepatitis)
• Current or recent (within 30 days) use of immunosuppressive agents.
• Use of any recombinant human erythropoietin formulation within the previous 30 days.
• Known or suspected carcinoma of the breast or prostate.
• Nephrosis, the nephrotic phase of nephritis.
• Hypercalcemia (serum calcium concentration \> 10.5 mg/dL).
• Pregnancy or lactation.
• Legal arrest or incarceration.
• Prohibition of pRBCs transfusion.

Sponsors & Collaborators

• Denver Health and Hospital Authority: lead

Study Sites (1)

Denver Health Medical Center

Denver, Colorado, 80204, United States

Location

MeSH Terms

Conditions

Wounds and Injuries; Anemia

Interventions

Ferric Oxide, Saccharated; Oxandrolone; Steroids

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Ferric Compounds; Iron Compounds; Inorganic Chemicals; Glucaric Acid; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Androstanols; Androstanes; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Fredric M Pieracci, MD, MPH

  Denver Health Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Surgery

Study Record Dates

• First Submitted: January 26, 2014
• First Posted: January 28, 2014
• Study Start: January 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: April 3, 2019

Record last verified: 2019-04

Locations

US (1)