ICU AnemiaPhase 1NCT02009943
Randomized Study Comparing Ferric Carboxymaltose to Iron Sucrose to Treat Fe Deficiency in the Surgically Critically Ill
A Phase 1 study testing Ferric carboxymaltose and Iron sucrose in people with ICU Anemia and Functional Iron Deficiency, run by Denver Health and Hospital Authority at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ICU Anemia, Functional Iron Deficiency
- What is being tested?
- Ferric carboxymaltose and Iron sucrose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2017to Sep 2017
- Phase
- Phase 1
- 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
- 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.
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 [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).
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- 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.
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 Pilot Study of Ferric Carboxymaltose as Compared to Iron Sucrose for the Treatment of Functional Iron Deficiency Associated With Surgical Critical Illness
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.
Read the detailed description
The inflammatory response associated with surgical critical illness rapidly induces a functional iron deficiency, characterized by hypoferremia, decreased transferrin saturation (TSAT), hyperferritinemia, and iron-deficient erythropoiesis (IDE). This functional iron deficiency both contributes to intensive care unit (ICU) anemia and increases the packed red blood cell (pRBCs) transfusion requirement.
The goals of iron supplementation of critically ill surgical patients are to reverse the serum iron debt, eliminate IDE, improve anemia, and decrease pRBCs transfusions. Issues surrounding iron supplementation of this patient population include formulation, dose, route of administration, and mitigation of the complications of iron overload, including infection.
The investigators first randomized clinical trial (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, the investigators compared intravenous iron sucrose 100 mg thrice weekly to placebo among critically ill trauma patients (NCT01180894). Iron supplementation at this dose increased the TSAT only marginally (and not above the normal range) and increased the serum ferritin concentration significantly; however, there was no effect on IDE, anemia, or pRBCs transfusion requirement. In no instance did iron supplementation increase the risk of infection, despite a relatively high incidence of marked hyperferritinemia (serum ferritin concentration > 1,000 ng/mL) in the iron group.
The severity of both the serum and bone marrow iron debts observed in these trials led us to investigate alternative dosing schemes that deliver larger quantities of bioavailable iron safely. Ferric carboxymaltose (FCM) is a novel iron-containing complex that allows for the administration of a large replenishment dose of iron (up to 750 mg) over a short infusion period. Several pharmacodynamic properties of FCM render it appealing for use in the treatment of functional iron deficiency associated with surgical critical illness, including a short infusion time, a controlled, sustained delivery of iron to target tissues over a relatively long period of time (up to one week), and minimal hypersensitivity reactions. Increased efficacy and comparable safety have been reported for FCM as compared to iron sucrose for treatment of outpatients with iron-deficiency anemia. There are currently no data regarding the efficacy of FCM for the indication of functional iron deficiency associated with surgical critical illness.
The aim of the current pilot trial is to compare two novel dosing schemes for treatment of functional iron deficiency in surgical ICU patients, both of which involve delivery of a larger total dose of iron as compared to both NCT00450177 and NCT01180894. 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
- Being tested
- Ferric carboxymaltose, Iron sucrose
- Keywords
- critical illness, iron supplementation, functional iron deficiency, ICU anemia, red blood cell transfusion
- Medical subject headings
- Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ferric carboxymaltoseDrug
Also called Injectafer
One time dosing
Iron sucroseDrug
Goal-directed dosing
| Study group | Role | What they receive |
|---|---|---|
| Ferric carboxymaltose (FDA IND pending) | Experimental | 15 mg/kg, up to 750 mg IV x 1 on the day of study enrollment. Receives: 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 Receives: Drug: Iron sucrose |
| Control | No intervention | No iron supplementation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%.
Measured: One week
Secondary outcomes (5)
Bone marrow iron debt
Bone marrow iron debt as measured by daily erythrocyte zinc protoporphyrin (eZPP) concentration. During normal erythropoiesis, iron is chelated to protoporphyrin IX to form heme. When inadequate iron is delivered to the bone marrow, zinc is substituted for iron, forming zinc protoporphyrin. An elevated eZPP is diagnostic of IDE and reflects the bone marrow iron supply regardless of total body iron.
Measured: One week
Serum ferritin concentration
The amount of ferritin in whole blood, measured in nanograms per deciliter
Measured: One week
Hemoglobin
The amount of hemoglobin in whole blood, measured in grams per deciliter
Measured: 28 days
Red blood cell transfusion requirement
Total number of units transfused.
Measured: 28 days
Nosocomial infections
Infections will be defined according to the US 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.
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 posted12 Dec 2013 (estimated)
- Study startFeb 2017 (estimated)
- Primary completionAug 2017 (estimated)
- Study completionSep 2017 (estimated)
Why it stopped: Inadequate funds
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ICU AnemiaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- 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 and Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02009943
- Sponsor's protocol ID
- COMIRB 13-3151
- Status last verified
- Jan 2018
- First submitted
- 5 Dec 2013
- Last updated
- 12 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Pilot Study of Ferric Carboxymaltose as Compared to Iron Sucrose for the Treatment of Functional Iron Deficiency Associated With Surgical Critical Illness
- ClinicalTrials.gov ID
- NCT02009943
- Acronym / sponsor ID
- COMIRB 13-3151
- Conditions
- ICU Anemia, Functional Iron Deficiency
- Keywords
- critical illness, iron supplementation, functional iron deficiency, ICU anemia, red blood cell transfusion
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Inadequate funds
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Denver Health and Hospital AuthorityUniversity, hospital or other
- Study start
- Feb 2017 (estimated)
- Primary completion
- Aug 2017 (estimated)
- Study completion
- Sep 2017 (estimated)
- First posted
- 12 Dec 2013 (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.
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.
Detailed description
The inflammatory response associated with surgical critical illness rapidly induces a functional iron deficiency, characterized by hypoferremia, decreased transferrin saturation (TSAT), hyperferritinemia, and iron-deficient erythropoiesis (IDE). This functional iron deficiency both contributes to intensive care unit (ICU) anemia and increases the packed red blood cell (pRBCs) transfusion requirement.
The goals of iron supplementation of critically ill surgical patients are to reverse the serum iron debt, eliminate IDE, improve anemia, and decrease pRBCs transfusions. Issues surrounding iron supplementation of this patient population include formulation, dose, route of administration, and mitigation of the complications of iron overload, including infection.
The investigators first randomized clinical trial (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, the investigators compared intravenous iron sucrose 100 mg thrice weekly to placebo among critically ill trauma patients (NCT01180894). Iron supplementation at this dose increased the TSAT only marginally (and not above the normal range) and increased the serum ferritin concentration significantly; however, there was no effect on IDE, anemia, or pRBCs transfusion requirement. In no instance did iron supplementation increase the risk of infection, despite a relatively high incidence of marked hyperferritinemia (serum ferritin concentration > 1,000 ng/mL) in the iron group.
The severity of both the serum and bone marrow iron debts observed in these trials led us to investigate alternative dosing schemes that deliver larger quantities of bioavailable iron safely. Ferric carboxymaltose (FCM) is a novel iron-containing complex that allows for the administration of a large replenishment dose of iron (up to 750 mg) over a short infusion period. Several pharmacodynamic properties of FCM render it appealing for use in the treatment of functional iron deficiency associated with surgical critical illness, including a short infusion time, a controlled, sustained delivery of iron to target tissues over a relatively long period of time (up to one week), and minimal hypersensitivity reactions. Increased efficacy and comparable safety have been reported for FCM as compared to iron sucrose for treatment of outpatients with iron-deficiency anemia. There are currently no data regarding the efficacy of FCM for the indication of functional iron deficiency associated with surgical critical illness.
The aim of the current pilot trial is to compare two novel dosing schemes for treatment of functional iron deficiency in surgical ICU patients, both of which involve delivery of a larger total dose of iron as compared to both NCT00450177 and NCT01180894. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ferric carboxymaltose (FDA IND pending) | Experimental | Drug: Ferric carboxymaltose15 mg/kg, up to 750 mg IV x 1 on the day of study enrollment. |
| Iron sucrose (FDA IND 109,877) | Active comparator | Drug: Iron sucroseIron 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 |
| Control | No intervention | –No iron supplementation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Anemia (hemoglobin < 12 g/dL).
- Functional iron deficiency:
- < 72 hours from ICU admission.
- Expected ICU length of stay ≥ 7 days.
Key exclusion criteria (15 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 [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).
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 |
|---|---|---|
| Ferric carboxymaltoseAlso: InjectaferOne time dosing | Drug | Ferric carboxymaltose (FDA IND pending) |
| Iron sucroseGoal-directed dosing | Drug | Iron sucrose (FDA IND 109,877) |
Primary outcome
Reversal of the serum iron debt as measured by the transferrin saturation
Time frame: One week
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%.
5 secondary outcomes
Bone marrow iron debt
Time frame: One week
Serum ferritin concentration
Time frame: One week
Hemoglobin
Time frame: 28 days
Red blood cell transfusion requirement
Time frame: 28 days
Nosocomial infections
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 12 Jan 2018.
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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 and Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ferric carboxymaltose and Iron sucrose in people with ICU Anemia and Functional Iron Deficiency, 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 7 inclusion and 15 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 12 Jan 2018. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Reversal of the 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 12 Jan 2018.