Functional Iron DeficiencyPhase 2NCT02047552
RCT of Goal-directed Iron Supplementation of Anemic, Critically Ill Trauma Patients, With and Without Oxandrolone
A Phase 2 study testing Iron sucrose and Oxandrolone in people with Functional Iron Deficiency and Trauma, run by Denver Health and Hospital Authority at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Functional Iron Deficiency, Trauma, Anemia
- What is being tested?
- Iron sucrose and Oxandrolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to Dec 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
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- Serum ferritin concentration > 28 ng/mL
- < 72 hours from ICU admission.
- Expected ICU length of stay ≥ 7 days.
Who cannot join
- 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).
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- 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.
- Stay of ≥ 48 hours duration in the ICU of a transferring hospital.
- History of intolerance or hypersensitivity to either iron or oxandrolone.
- Moribund state in which death was imminent.
Trial locations and contacts
1 site in 1 country.
United States1 site
Denver Health Medical Center
Denver, Colorado, 80204
About this study
Official title: A Randomized Controlled Pilot Study of Goal-directed Iron Supplementation of Anemic, Critically Ill Trauma Patients With Functional Iron Deficiency, With and Without Oxandrolone
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.
Read the detailed description
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.
- Conditions
- Functional Iron Deficiency, Trauma, Anemia
- Being tested
- Iron sucrose, Oxandrolone, IV iron placebo, Oxandrolone placebo
- Keywords
- trauma, iron, anemia, red blood cell transfusion
- Medical subject headings
- Wounds and Injuries, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Iron sucroseDrug
Also called Fe
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.
OxandroloneDrug
Also called Steroid
10 mg PO Q12 hours for seven days
IV iron placeboDrug
Also called Fe placebo
100 mL normal saline
Oxandrolone placeboDrug
Also called Steroid placebo
similar color and size sugar pill
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Iron sucrose; Drug: Oxandrolone placebo |
| Oxandrolone | Active comparator | Oxandrolone 10 mg PO q12 hours will be dosed for seven days. Receives: 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. Receives: 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 Receives: Drug: IV iron placebo; Drug: Oxandrolone placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum iron debt (as measured by the transferrin saturation)
The transferrin saturation will be measured at baseline and daily thereafter for one week
Measured: One week
Secondary outcomes (9)
Bone marrow iron debt (as measured by the zinc protoporphyrin)
Zinc protoporphyrin will be measured at baseline and daily thereafter for one week
Measured: one week
Serum ferritin concentration
The serum ferritin concentration will be measured at baseline and daily thereafter for one week
Measured: one week
serum hepcidin concentration
The serum hepcidin concentration will be measured at baseline and daily thereafter for one week.
Measured: one week
Liver function tests
Liver function tests will be measured at baseline and daily thereafter for one week.
Measured: one week
Erythropoeitin concentration
The serum erythropoeitin concentration will be measured at baseline and daily thereafter for one week.
Measured: one week
Red blood cell transfusion requirement
The incidence and number of red blood cell transfusions will be collected for 28 days.
Measured: 28 days
Hemoglobin
The hemoglobin concentration will be measured at baseline and daily thereafter for 28 days.
Measured: 28 days
Infections
The incidence, types, and number of infections will be collected for 28 days.
Measured: 28 days
All cause mortality
All cause mortality will be collected for 28 days
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2014 (estimated)
- Study startJan 2015
- Primary completionDec 2017
- Study completionDec 2017
Why it stopped: No Participants enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Functional Iron DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Denver Health and Hospital Authority
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fredric Pieracci, Denver Health and Hospital Authority
- Investigators
- Fredric M Pieracci, MD, MPH, Principal investigator, Denver Health Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02047552
- Sponsor's protocol ID
- 14-0167
- Status last verified
- Apr 2019
- First submitted
- 26 Jan 2014
- Last updated
- 3 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Pilot Study of Goal-directed Iron Supplementation of Anemic, Critically Ill Trauma Patients With Functional Iron Deficiency, With and Without Oxandrolone
- ClinicalTrials.gov ID
- NCT02047552
- Acronym / sponsor ID
- 14-0167
- Conditions
- Functional Iron Deficiency, Trauma, Anemia
- Keywords
- trauma, iron, anemia, red blood cell transfusion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No Participants enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Denver Health and Hospital AuthorityUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 28 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Iron sucrose | Active comparator | Drug: Iron sucrose, Drug: Oxandrolone placeboIron 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. |
| Oxandrolone | Active comparator | Drug: Oxandrolone, Drug: IV iron placeboOxandrolone 10 mg PO q12 hours will be dosed for seven days. |
| Iron sucrose + oxandrolone | Experimental | Drug: Iron sucrose, Drug: OxandroloneCombination goal-directed iron sucrose (as described in the iron sucrose only arm) and oxandrolone (as described in the oxandrolone only arm) for seven days. |
| IV iron placebo and Oxandrolone placebo | Placebo comparator | Drug: IV iron placebo, Drug: Oxandrolone placebo100 mL normal saline in place of iron and similar color and size sugar pill for Oxandrolone placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Informed consent from patient or patient representative.
- Trauma patient
- Anemia (hemoglobin < 12 g/dL).
- Functional iron deficiency:
- < 72 hours from ICU admission.
Key exclusion criteria (18 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Iron sucroseAlso: FeIron 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, Iron sucrose + oxandrolone |
| OxandroloneAlso: Steroid10 mg PO Q12 hours for seven days | Drug | Iron sucrose + oxandrolone, Oxandrolone |
| IV iron placeboAlso: Fe placebo100 mL normal saline | Drug | IV iron placebo and Oxandrolone placebo, Oxandrolone |
| Oxandrolone placeboAlso: Steroid placebosimilar color and size sugar pill | Drug | IV iron placebo and Oxandrolone placebo, Iron sucrose |
Primary outcome
Serum iron debt (as measured by the transferrin saturation)
Time frame: One week
The transferrin saturation will be measured at baseline and daily thereafter for one week
9 secondary outcomes
Bone marrow iron debt (as measured by the zinc protoporphyrin)
Time frame: one week
Serum ferritin concentration
Time frame: one week
serum hepcidin concentration
Time frame: one week
Liver function tests
Time frame: one week
Erythropoeitin concentration
Time frame: one week
Red blood cell transfusion requirement
Time frame: 28 days
Hemoglobin
Time frame: 28 days
Infections
Time frame: 28 days
All cause mortality
Time frame: 28 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2019.
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The Impact of IV Iron on Exercise Capacity and Quality of Life in Pulmonary Hypertension
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fredric M Pieracci, MD, MPH principal investigator
Denver Health Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Iron sucrose and Oxandrolone in people with Functional Iron Deficiency and Trauma, run by Denver Health and Hospital Authority at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 3 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum iron debt (as measured by the transferrin saturation) (time frame: One week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2019.