Critical IllnessSOFINCT01443624
Evaluation of Oxidative Stress Induced by Iron Injection in Healthy Volunteers and Critical Care Patients
A study testing critical care patients venofer in people with Critical Illness, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The purpose of this study is to evaluate the pro-oxidant toxicity of iron injections in critically ill patients and in healthy volunteers. The investigators hypothesize that the inflammatory state of critically ill patients will reduce the oxydative stress induced by iron injections, compared to the one induced in… Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Critical Illness
- What is being tested?
- critical care patients venofer
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteFrance
- Study dates
- Oct 2011to Aug 2013
- Phase
- Interventional
- 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 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Man or woman hospitalized in critical care unit,
- between 18 and 90 years old
- clinical examination completed
- written consent from the patient or a patient's relative depending on the awareness of the patient
- an iron injection has been prescribed by the responsible physician to the patient
- anemia defined as hemoglobin level ≤11 g/dl
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- iron deficiency define by at least one of the following criteria :
- ferritin < 100 μg/l
- ferritin between 100 and 300 μg/l with transferrin saturation < 20%,
- soluble transferrin receptor (RsTf) ≥1,4 mg/l,
- ratio RsTf/log(ferritin) ≥0,7,
- blood loss ≥ 1 blood weight.
Who cannot join
- do not subscribe to the french health insurance program
- Pregnancy or nursing
- past medical history of iron overload or disfunction in iron metabolism (= primary or secondary hemochromatosis)
- Recent bacteremia defined as positive in the 48 hours preceding the injection. Having a non positive hemoculture is not an exclusion criteria
- Suspicion of a novel current infection defined by a new fever with temperature over >38°5 for at least three times during the last 48hours. A persisting fever for more than 48 hours without argument for a new infection is not an exclusion criteria.
- known allergia to the iron- hydroxide complex or one of the excipient
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- active chronic alcoholism
- oral iron treatment during the last 24 hours. Usage of antioxidant (vitamin C, vitamin E) within the 24 hours preceding the iron injection.
- person participating to another clinical trial or being in the exclusion phase of a clinical trial
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Oxidative Stress Induced by Iron Injection in Healthy Volunteers Versus Critical Care Patients
The purpose of this study is to evaluate the pro-oxidant toxicity of iron injections in critically ill patients and in healthy volunteers. The investigators hypothesize that the inflammatory state of critically ill patients will reduce the oxydative stress induced by iron injections, compared to the one induced in healthy volunteers. It will be an open "proof-of-concept" study aimed at evaluating iron toxicity in critically ill patients (n=40) as compared to healthy volunteers (n=40).
The investigators will compare the oxidative stress (principal judgment criteria= 8-iso-PGF2α) following a 100 mg injection of iron (at T0, T2, T6 and T24 hours post injection) in both groups and the investigators will compare the effect of repeated injections in the critically ill patients.
Read the detailed description
Anemia is frequent among critically ill patients, with 60% of the patients being anemic at admission and more than 80% at discharge. This anemia is associated with an increased MORBI-mORTALITY. However, therapeutic options, mainly transfusion and erythropoietin, are disappointing. There is a remaining therapeutic option, iron injection, which has not been fully evaluated because of potential restrictions: inflammation may prevent its efficacy, and iron could be toxic, notably through the generation of oxidative stress. Our research is aimed at exploring the benefit of iron treatment in the critical care anemia.
The investigators already demonstrated in a MURIN model of critical care anemia that the master regulator of iron metabolism, hepcidin, is repressed and that iron can be mobilized from the stores despite inflammation. In addition, in an observational human study, the investigators reported that 25% of critically ill patients had iron deficiency and low to normal hepcidin levels.
All together, these data indicate that iron therapy may be beneficial in this situation. In the present study, the investigators evaluate the toxicity of iron in that context of critical care anemia. Iron, especially non-transferrin bound iron, is known to induce the generation of oxygen-derived free radicals through the Fenton reaction. However, the generation of oxidative stress secondary to iron injection has not been investigated in the critically ill. In our animal model, preliminary data indicate that the production of oxidative stress in the serum following iron injection may be prevented by inflammation.
Objectives: To evaluate the pro-oxidant toxicity of iron injections in critically ill patients and in healthy volunteers. The investigators hypothesize that the oxidative stress will be reduced in critically ill as compared to healthy volunteers
Human study : It will be an open "proof-of-concept" study aiming at evaluating iron toxicity in critically ill patients (n=40) as compared to healthy volunteers (n=40).
The investigators will compare the oxidative stress (principal judgment criteria= 8-iso-PGF2α) following a 100 mg injection of iron (at T0, T2, T6 and T24 hours post injection) in both groups and the investigators will compare the effect of repeated injections in the critically ill patients.
Perspectives:
This study should confirm that iron does not produce more oxidant stress in critically ill patients than in healthy volunteers. The animal study should help to precise the efficacy of this treatment, in addition to its toxicity. All these results will help to design a phase III randomized study of intravenous iron in critically ill anemic patients
- Conditions
- Critical Illness
- Being tested
- critical care patients venofer
- Keywords
- iron, critical illness, oxidative stress
- Medical subject headings
- Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
critical care patients venoferDrug
Also called iron (ferric hydroxide sucrose) injection
100mg IV in one hour (in critically ill patients the injection could be repeated on day 2 (200mg) and 4 (100mg) depending on treatment
| Study group | Role | What they receive |
|---|---|---|
| critical care patients venofer | Experimental | Critically ill patients are injected with Venofer (ferric hydroxide sucrose) 100mg IV in one hour (in critically ill patients the injection could be repeated on day 2 (200mg) and 4 (100mg) depending on treatment Receives: Drug: critical care patients venofer |
What is being measured
The primary outcome is the main question the study is designed to answer.
serum 8-iso-PGF2α
oxidative stress
Measured: 0 hours
serum 8-iso-PGF2α
oxidative stress
Measured: 2 hours
serum 8-iso-PGF2α
oxidative stress
Measured: 6 hours
serum 8-iso-PGF2α
oxidative stress
Measured: 24 hours
Secondary outcomes (4)
Advanced Oxidized Protein Product
oxidative stress
Measured: 0 hours
Advanced Oxidized Protein Product
oxidative stress
Measured: 2 hours
Advanced Oxidized Protein Product
oxidative stress
Measured: 6 hours
Advanced Oxidized Protein Product
oxidative stress
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2011 (estimated)
- Study startOct 2011
- Primary completionJan 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sigismond Lasocki, MD PhD, Principal investigator, University Hospital, Angers
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01443624
- Sponsor's protocol ID
- P101104
- Other IDs
- 2011-000819-10
- Acronym
- SOFI
- Status last verified
- Aug 2013
- First submitted
- 27 Sep 2011
- Last updated
- 14 Aug 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Oxidative Stress Induced by Iron Injection in Healthy Volunteers Versus Critical Care Patients
- ClinicalTrials.gov ID
- NCT01443624
- Acronym / sponsor ID
- SOFI / P101104
- Conditions
- Critical Illness
- Keywords
- iron, critical illness, oxidative stress
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Jan 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 30 Sep 2011 (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 study is to evaluate the pro-oxidant toxicity of iron injections in critically ill patients and in healthy volunteers. The investigators hypothesize that the inflammatory state of critically ill patients will reduce the oxydative stress induced by iron injections, compared to the one induced in healthy volunteers. It will be an open "proof-of-concept" study aimed at evaluating iron toxicity in critically ill patients (n=40) as compared to healthy volunteers (n=40).
The investigators will compare the oxidative stress (principal judgment criteria= 8-iso-PGF2α) following a 100 mg injection of iron (at T0, T2, T6 and T24 hours post injection) in both groups and the investigators will compare the effect of repeated injections in the critically ill patients.
Detailed description
Anemia is frequent among critically ill patients, with 60% of the patients being anemic at admission and more than 80% at discharge. This anemia is associated with an increased MORBI-mORTALITY. However, therapeutic options, mainly transfusion and erythropoietin, are disappointing. There is a remaining therapeutic option, iron injection, which has not been fully evaluated because of potential restrictions: inflammation may prevent its efficacy, and iron could be toxic, notably through the generation of oxidative stress. Our research is aimed at exploring the benefit of iron treatment in the critical care anemia.
The investigators already demonstrated in a MURIN model of critical care anemia that the master regulator of iron metabolism, hepcidin, is repressed and that iron can be mobilized from the stores despite inflammation. In addition, in an observational human study, the investigators reported that 25% of critically ill patients had iron deficiency and low to normal hepcidin levels.
All together, these data indicate that iron therapy may be beneficial in this situation. In the present study, the investigators evaluate the toxicity of iron in that context of critical care anemia. Iron, especially non-transferrin bound iron, is known to induce the generation of oxygen-derived free radicals through the Fenton reaction. However, the generation of oxidative stress secondary to iron injection has not been investigated in the critically ill. In our animal model, preliminary data indicate that the production of oxidative stress in the serum following iron injection may be prevented by inflammation.
Objectives: To evaluate the pro-oxidant toxicity of iron injections in critically ill patients and in healthy volunteers. The investigators hypothesize that the oxidative stress will be reduced in critically ill as compared to healthy volunteers
Human study : It will be an open "proof-of-concept" study aiming at evaluating iron toxicity in critically ill patients (n=40) as compared to healthy volunteers (n=40).
The investigators will compare the oxidative stress (principal judgment criteria= 8-iso-PGF2α) following a 100 mg injection of iron (at T0, T2, T6 and T24 hours post injection) in both groups and the investigators will compare the effect of repeated injections in the critically ill patients.
Perspectives:
This study should confirm that iron does not produce more oxidant stress in critically ill patients than in healthy volunteers. The animal study should help to precise the efficacy of this treatment, in addition to its toxicity. All these results will help to design a phase III randomized study of intravenous iron in critically ill anemic patients
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| critical care patients venofer | Experimental | Drug: critical care patients venoferCritically ill patients are injected with Venofer (ferric hydroxide sucrose) 100mg IV in one hour (in critically ill patients the injection could be repeated on day 2 (200mg) and 4 (100mg) depending on treatment |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Man or woman hospitalized in critical care unit,
- between 18 and 90 years old
- clinical examination completed
- written consent from the patient or a patient's relative depending on the awareness of the patient
- an iron injection has been prescribed by the responsible physician to the patient
Key exclusion criteria (9 listed)
- do not subscribe to the french health insurance program
- Pregnancy or nursing
- past medical history of iron overload or disfunction in iron metabolism (= primary or secondary hemochromatosis)
- Recent bacteremia defined as positive in the 48 hours preceding the injection. Having a non positive hemoculture is not an exclusion criteria
- Suspicion of a novel current infection defined by a new fever with temperature over >38°5 for at least three times during the last 48hours. A persisting fever for more than 48 hours without argument for a new infection is not an exclusion criteria.
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 |
|---|---|---|
| critical care patients venoferAlso: iron (ferric hydroxide sucrose) injection100mg IV in one hour (in critically ill patients the injection could be repeated on day 2 (200mg) and 4 (100mg) depending on treatment | Drug | critical care patients venofer |
Primary outcome
serum 8-iso-PGF2α
Time frame: 0 hours
oxidative stress
serum 8-iso-PGF2α
Time frame: 2 hours
oxidative stress
serum 8-iso-PGF2α
Time frame: 6 hours
oxidative stress
serum 8-iso-PGF2α
Time frame: 24 hours
oxidative stress
4 secondary outcomes
Advanced Oxidized Protein Product
Time frame: 0 hours
Advanced Oxidized Protein Product
Time frame: 2 hours
Advanced Oxidized Protein Product
Time frame: 6 hours
Advanced Oxidized Protein Product
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2013.
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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.
Sigismond Lasocki, MD PhD principal investigator
University Hospital, Angers
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing critical care patients venofer in people with Critical Illness, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 12 inclusion and 9 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: finished, as of the sponsor's last update on 14 Aug 2013. 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 France. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 8-iso-PGF2α (time frame: 0 hours). The study lists 4 primary outcomes in all. 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 14 Aug 2013.