A Phase 2 interventional study of Iron sucrose and Oxandrolone in Functional Iron Deficiency, Trauma and Anemia, sponsored by Denver Health and Hospital Authority. Withdrawn at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-04-03.
Sponsored by Denver Health and Hospital Authority · Phase 2, Interventional, and Treatment
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.
The inflammatory response associated with traumatic critical illness rapidly induces a functional iron deficiency, characterized by hypoferremia, decreased transferrin saturation (TSAT), hyperferritinemia, and iron-deficient erythropoiesis (IDE). These derangements in iron metabolism are primarily related to upregulation of the iron regulatory protein hepcidin, which inhibits ferroportin-mediated release of iron from both duodenal enterocytes and macrophages. The resultant functional iron deficiency both contributes to intensive care unit (ICU) anemia and increases the packed red blood cell (pRBCs) transfusion requirement.
Treatment strategies for functional iron deficiency in critically ill patients may be divided broadly into (1) iron supplementation and (2) mitigation of the effects of hepcidin. The goals of treatment are to reverse the serum iron debt, eliminate IDE, improve anemia, and ultimately decrease pRBCs transfusions. Given that approximately 90% of critically ill trauma patients with an ICU length of stay (LOS) ≥ 7 days receive at least one pRBCs transfusion, any strategy that has even a modest impact upon the transfusion requirement is likely to improve overall health outcomes substantially.
Issues surrounding iron supplementation of critically ill patients include formulation, dose, route of administration, hepcidin antagonism, and mitigation of the complications of iron overload, particularly infection. Our first RCT of iron supplementation of critically ill surgical patients compared enteral ferrous sulfate 325 mg thrice daily to placebo (NCT00450177). Although a significant reduction in pRBCs transfusion requirement for the iron group was observed, low injury severity, intolerance of enteral medications, and a predominance of traumatic brain injury limited generalizability. In a second multicenter RCT, we compared intravenous iron sucrose 100 mg thrice weekly to placebo among critically ill trauma patients (NCT01180894, NTI-ICU-008-01) [8]. Iron supplementation using this generic dosing scheme did not impact the serum iron concentration, TSAT, IDE, anemia, or pRBCs transfusion requirement. Rather, iron supplementation accumulated as ferritin as evidenced by a significantly increased serum ferritin concentration in the iron as compared to the placebo group at all time points. Iron supplementation did not increase the risk of infection in either trial, despite a relatively high incidence of marked hyperferritinemia (serum ferritin concentration > 1,000 ng/mL) in the iron group.
The results of these trials suggest that iron supplementation alone, and using a generic dosing scheme, is ineffective. The current pilot trial aims to build upon the findings of the prior two RCTs by incorporating both goal-directed iron supplementation and hepcidin antagonism. The hypothesis is that the combination of goal directed iron supplementation and hepcidin mitigation will safely eliminate both the serum and bone marrow iron debt of anemic, critically ill trauma patients with functional iron deficiency.
644 studies on the registry are indexed under Anemia, Iron-Deficiency; 105 are open to participants now.
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Functional iron deficiency:
Exclusion Criteria:
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 10 mg PO q12 hours will be dosed for seven days.
Drug: Oxandrolone · Drug: IV iron placebo
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
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
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
10 mg PO Q12 hours for seven days
Also known as: Steroid
100 mL normal saline
Also known as: Fe placebo
similar color and size sugar pill
Also known as: Steroid placebo
Serum iron debt (as measured by the transferrin saturation)
The transferrin saturation will be measured at baseline and daily thereafter for one week
Time frame: One week
Bone marrow iron debt (as measured by the zinc protoporphyrin)
Zinc protoporphyrin will be measured at baseline and daily thereafter for one week
Time frame: one week
Serum ferritin concentration
The serum ferritin concentration will be measured at baseline and daily thereafter for one week
Time frame: one week
serum hepcidin concentration
The serum hepcidin concentration will be measured at baseline and daily thereafter for one week.
Time frame: one week
Liver function tests
Liver function tests will be measured at baseline and daily thereafter for one week.
Time frame: one week
Erythropoeitin concentration
The serum erythropoeitin concentration will be measured at baseline and daily thereafter for one week.
Time frame: one week
Red blood cell transfusion requirement
The incidence and number of red blood cell transfusions will be collected for 28 days.
Time frame: 28 days
Hemoglobin
The hemoglobin concentration will be measured at baseline and daily thereafter for 28 days.
Time frame: 28 days
Infections
The incidence, types, and number of infections will be collected for 28 days.
Time frame: 28 days
All cause mortality
All cause mortality will be collected for 28 days
Time frame: 28 days
This study is withdrawn, as verified in Apr 2019. You cannot join it, but the record below documents what was studied.
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Denver Health and Hospital Authority