AnemiaPhase 3EPO-ICU-FSNCT05080049
Erythropoietin to Improve Critical Care Patient Outcomes
A Phase 3 study testing Erythropoietin in people with Anemia and Intensive Care, run by University Hospital, Angers at 2 sites in France.
Trial summary
Recently, the french societies for critical care (SFAR and SRLF) produced guidelines for anemia treatment in critically ill patients that recommend the use of erythropoietin (EPO) in these patients, but the european society (ESICM) recommended against the use of EPO in this patients, despite recent meta analysis… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anemia, Intensive Care
- What is being tested?
- Erythropoietin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 2 sitesFrance
- Study dates
- 28 Jan 2022to 31 Dec 2022
- Phase
- Phase 3
- 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
- Adult patients (age > 18 years),
- admitted to intensive care for more than 72 hours and less than 7 days
- who have received invasive ventilatory support and/or treatment with a vasoactive agent for at least one day since admission
- with an Hb level < 12 g/dl,
- with consent from the patient or patient's relative (or emergency inclusion procedure).
Who cannot join
- Moribund patient,
- Current hospitalization for acute coronary syndrome,
- Recent history of thromboembolic event (< 3 months),
- Uncontrolled hypertension despite adequate antihypertensive therapy,
- Myelodysplasia or chronic pathology requiring iterative transfusions,
- EPO treatment within the last 30 days,
Show all 14Show fewer
- Participation in another interventional trial of an erythropoiesis-stimulating agent or anemia treatment,
- Expected discharge from the intensive care unit within 24 hours,
- Known hypersensitivity to EPO or any of its components,
- A history of erythroblastopenia following erythropoietin therapy
- Pregnant, breast-feeding or parturient woman
- Person deprived of liberty by judicial or administrative decision
- Person under forced psychiatric care
- Person under a legal protection measure.
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: Erythropoietin to Improve Critical Care Patient Outcomes: Feasibility Study of a Multicenter, Randomized, Placebo-controlled Trial of Subcutaneous Erythropoietin Injection for Intensive Care Patients
Recently, the french societies for critical care (SFAR and SRLF) produced guidelines for anemia treatment in critically ill patients that recommend the use of erythropoietin (EPO) in these patients, but the european society (ESICM) recommended against the use of EPO in this patients, despite recent meta analysis showing a lower mortality in patients treated with EPO.
Nevertheless, RCT on EPO in the ICU are quite all, new data are thus needed. Before conducting a large study on EPO in anemic patients in the ICU, we propose to cinduct a feasability RCT to evaluate the feasability of such a study.
Read the detailed description
Anemia is very common in intensive care patients, affecting approximately two-thirds of patients on admission, with a mean admission hemoglobin (Hb) level of 11.0 g/dl. The severity of anemia is associated with increased morbidity and mortality. Its pathophysiology is complex, involving blood loss (from repeated blood sampling, invasive procedures, surgical interventions, etc.) and inflammation. The latter is responsible for a decrease in endogenous erythropoietin (EPO) production and a decreased bone marrow response, which can be very prolonged (half of the patients discharged from ICU with anemia are still anemic at 6 months of discharge, with low levels of EPO, compared to the observed Hb levels). On this basis, several randomized clinical trials (RCTs) evaluating the effect of EPO on the transfusion rate in this population were performed in the 1990s-2000s. The authors showed a modest reduction in blood transfusion, which was not considered clinically relevant in view of the cost of EPO at that time.
Since then, meta-analyses evaluating the benefits and risks of EPO in intensive care patients suggest a positive impact of EPO on mortality. The largest, including 34 studies (and 930,470 patients) reports a reduction in the relative risk of mortality of 0.76, 95% CI [0.61 - 0.92]. Beyond the reduction in red blood cell transfusions, the benefit of EPO could be directly due to its erythropoietic effect (correction of anemia) and/or its anti-inflammatory/anti-apoptotic properties. Based on this literature, the French critical care societies have recently recommended the use of EPO. However, the European Society of Intensive Care Medicine (ESICM) recently recommended against the use of EPO, based on the same literature, but suggested that the benefit of EPO should be evaluated. Indeed, the main obstacle to recommending the use of EPO seems to be economic, whereas the arrival on the market of biosimilar molecules has significantly reduced these costs.
Most of the trials on EPO in critical care patients (and included in the meta-analyses) are quite old (about 15 years) and none of them had mortality as primary endpoint. In addition, transfusion practices and the quality of blood products have changed significantly over the years. In this context of disagreement on the recommendations for the use of EPO in these patients, but of potential benefit on mortality, there is an urgent need to evaluate whether EPO decreases mortality in adult anemic patients admitted to intensive care. However, calculation of the number of patients needed to evaluate the benefit of EPO on mortality in this population yields a number of patients to be included of the order of 1800-2000 patients.
Before considering the implementation of a multicenter study involving such a large number of patients, a pilot study evaluating the feasibility and inclusion capacity for such a study seems indispensable according to the latest CONSORT recommendations.
- Conditions
- Anemia, Intensive Care
- Being tested
- Erythropoietin, Placebo
- Keywords
- Anemia, Intensive Care, Feasibility study, Erythropoietin
- Medical subject headings
- Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErythropoietinDrug
Patients receive a subcutaneous injection of 40,000 IU of erythropoietin alfa or zêta, repeated weekly until Day 28 (if the hemoglobin level is <12 g/dl and the patient remains hospitalized).
The study treatments are administered by an open-label nurse. In both groups, before each injection, iron deficiency (defined as reticulocyte Hb <29 pg, or hepcidin <41 µg/L, or ferritin <100 µg/L, or ferritin <300 µg/L with transferrin saturation <20%) is treated with intravenous iron infusion (depending on the product available at the center). A restrictive transfusion strategy is recommended as long as the patient remains in the ICU, according to recent recommendations.
Six visits are scheduled: V1 for inclusion and the first injection, V2 at Day 7(±2 days) for the second injection, V3 at Day 14(±2 days) for the third injection, V4 at Day 21(±2 days) for the fourth injection, V5 at Day 28(±2 days) for the fifth injection.
PlaceboDrug
In the control arm, patients receive a subcutaneous injection of placebo (0.9% NaCl) according to the same schedule.
The study treatments are administered by an open-label nurse. In both groups, before each injection, iron deficiency (defined as reticulocyte Hb <29 pg, or hepcidin <41 µg/L, or ferritin <100 µg/L, or ferritin <300 µg/L with transferrin saturation <20%) is treated with intravenous iron infusion (depending on the product available at the center). A restrictive transfusion strategy is recommended as long as the patient remains in the ICU, according to recent recommendations.
Six visits are scheduled: V1 for inclusion and the first injection, V2 at Day 7(±2 days) for the second injection, V3 at Day 14(±2 days) for the third injection, V4 at Day 21(±2 days) for the fourth injection, V5 at Day 28(±2 days) for the fifth injection.
| Study group | Role | What they receive |
|---|---|---|
| erythropoietin | Experimental | Erythropoietin alpha or theta 40,000 UI (1 ml) sc each week if Hb <12 g/dL (for maximum 5 weeks) Receives: Drug: Erythropoietin |
| Placebo | Placebo comparator | saline sc injection (1 ml) each weeks if Hb <12 g/dL, for a maximum of 5 weeks, Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment rate
≥50% of eligible patients will need to be enrolled, but the trial will not be feasible if the inclusion rate is ≤ 25% or less
Measured: 90 days
Adherence to allocation groups
A high level of matching of randomization and group allocation should be achieved, with at least 85% of included patients receiving protocol-allocated treatment, but if ≤ 65% patients receive protocol-allocated treatment, the trial is not feasible
Measured: 90 days
Completion of follow-up of included patients
≥ 85% of patients should be followed through to the end of follow-up, but if <65% patients are followed through to the last visit, the protocol will not be feasible
Measured: 90 days
Secondary outcomes (15)
The proportion of patients lost to follow-up at each visit
The proportion of patients lost to follow-up at each visit
Measured: 7, 14, 21, 28 and 90 days
The rate of missing data for mortality outcome
The rate of missing data for mortality outcome
Measured: 90 days
The rate of compliance with the therapeutic protocol at each visit for inpatients
The rate of compliance with the therapeutic protocol at each visit for inpatients
Measured: 7, 14, 21, and 28 days
Mean serum hemoglobin value
Mean serum hemoglobin value
Measured: 28 days
ICU mortality
ICU mortality
Measured: up to 90 days
Hospital mortality
Hospital mortality
Measured: up to 90 days
ICU length of stay
ICU length of stay
Measured: up to 90 days
Hospital length of stay
Hospital length of stay
Measured: up to 90 days
Blood transfusion
Proportion of patients who received at least one red blood cell transfusion
Measured: 90 days
number of red blood cells transfused
number of red blood cells transfused
Measured: 90 days
90 days survival analysis
90 days survival analysis
Measured: 90 days
Occurrence of hospital readmission (censored at 90 days after inclusion),
at least one hospital readmission after the hospital discharge
Measured: 90 days
Number of days living at home (or previous place of living)
Number of days living at home (or previous place of living) at D90
Measured: 90 days
Quality of life measured by the EQ-5D 5L scale, EuroQol 5 dimensions
The value from this scale records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine'. The scale is rated from 0 to 100.
Measured: 90 days
Proportion of patients with a thromboembolic event
Thrombolic event: pulmonary embolism, venous or arterial thrombosis
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2021
- Study start28 Jan 2022
- Primary completion2 Sep 2022
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnemiaStudies of the same condition, open and under way.
- More trials run by University Hospital, AngersThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Angers
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Maxime Léger, MD, Principal investigator, University Hospital, AngersSigismond Lasocki, MD, Study director, University Hospital, Angers
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05080049
- Sponsor's protocol ID
- EPO-ICU-FS
- Acronym
- EPO-ICU-FS
- Status last verified
- Sep 2022
- First submitted
- 20 Sep 2021
- Last updated
- 10 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Erythropoietin to Improve Critical Care Patient Outcomes: Feasibility Study of a Multicenter, Randomized, Placebo-controlled Trial of Subcutaneous Erythropoietin Injection for Intensive Care Patients
- ClinicalTrials.gov ID
- NCT05080049
- Acronym / sponsor ID
- EPO-ICU-FS / EPO-ICU-FS
- Conditions
- Anemia, Intensive Care
- Keywords
- Anemia, Intensive Care, Feasibility study, Erythropoietin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 42 participants (actual)
- Lead sponsor
- University Hospital, AngersOther government
- Study start
- 28 Jan 2022 (actual)
- Primary completion
- 2 Sep 2022 (actual)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 15 Oct 2021 (actual)
- 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.
Recently, the french societies for critical care (SFAR and SRLF) produced guidelines for anemia treatment in critically ill patients that recommend the use of erythropoietin (EPO) in these patients, but the european society (ESICM) recommended against the use of EPO in this patients, despite recent meta analysis showing a lower mortality in patients treated with EPO.
Nevertheless, RCT on EPO in the ICU are quite all, new data are thus needed. Before conducting a large study on EPO in anemic patients in the ICU, we propose to cinduct a feasability RCT to evaluate the feasability of such a study.
Detailed description
Anemia is very common in intensive care patients, affecting approximately two-thirds of patients on admission, with a mean admission hemoglobin (Hb) level of 11.0 g/dl. The severity of anemia is associated with increased morbidity and mortality. Its pathophysiology is complex, involving blood loss (from repeated blood sampling, invasive procedures, surgical interventions, etc.) and inflammation. The latter is responsible for a decrease in endogenous erythropoietin (EPO) production and a decreased bone marrow response, which can be very prolonged (half of the patients discharged from ICU with anemia are still anemic at 6 months of discharge, with low levels of EPO, compared to the observed Hb levels). On this basis, several randomized clinical trials (RCTs) evaluating the effect of EPO on the transfusion rate in this population were performed in the 1990s-2000s. The authors showed a modest reduction in blood transfusion, which was not considered clinically relevant in view of the cost of EPO at that time.
Since then, meta-analyses evaluating the benefits and risks of EPO in intensive care patients suggest a positive impact of EPO on mortality. The largest, including 34 studies (and 930,470 patients) reports a reduction in the relative risk of mortality of 0.76, 95% CI [0.61 - 0.92]. Beyond the reduction in red blood cell transfusions, the benefit of EPO could be directly due to its erythropoietic effect (correction of anemia) and/or its anti-inflammatory/anti-apoptotic properties. Based on this literature, the French critical care societies have recently recommended the use of EPO. However, the European Society of Intensive Care Medicine (ESICM) recently recommended against the use of EPO, based on the same literature, but suggested that the benefit of EPO should be evaluated. Indeed, the main obstacle to recommending the use of EPO seems to be economic, whereas the arrival on the market of biosimilar molecules has significantly reduced these costs.
Most of the trials on EPO in critical care patients (and included in the meta-analyses) are quite old (about 15 years) and none of them had mortality as primary endpoint. In addition, transfusion practices and the quality of blood products have changed significantly over the years. In this context of disagreement on the recommendations for the use of EPO in these patients, but of potential benefit on mortality, there is an urgent need to evaluate whether EPO decreases mortality in adult anemic patients admitted to intensive care. However, calculation of the number of patients needed to evaluate the benefit of EPO on mortality in this population yields a number of patients to be included of the order of 1800-2000 patients.
Before considering the implementation of a multicenter study involving such a large number of patients, a pilot study evaluating the feasibility and inclusion capacity for such a study seems indispensable according to the latest CONSORT recommendations.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| erythropoietin | Experimental | Drug: ErythropoietinErythropoietin alpha or theta 40,000 UI (1 ml) sc each week if Hb <12 g/dL (for maximum 5 weeks) |
| Placebo | Placebo comparator | Drug: Placebosaline sc injection (1 ml) each weeks if Hb <12 g/dL, for a maximum of 5 weeks, |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult patients (age > 18 years),
- admitted to intensive care for more than 72 hours and less than 7 days
- who have received invasive ventilatory support and/or treatment with a vasoactive agent for at least one day since admission
- with an Hb level < 12 g/dl,
- with consent from the patient or patient's relative (or emergency inclusion procedure).
Key exclusion criteria (14 listed)
- Moribund patient,
- Current hospitalization for acute coronary syndrome,
- Recent history of thromboembolic event (< 3 months),
- Uncontrolled hypertension despite adequate antihypertensive therapy,
- Myelodysplasia or chronic pathology requiring iterative transfusions,
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 |
|---|---|---|
| ErythropoietinPatients receive a subcutaneous injection of 40,000 IU of erythropoietin alfa or zêta, repeated weekly until Day 28 (if the hemoglobin level is <12 g/dl and the patient remains hospitalized). The study treatments are administered by an open-label nurse. In both groups, before each injection, iron deficiency (defined as reticulocyte Hb <29 pg, or hepcidin <41 µg/L, or ferritin <100 µg/L, or ferritin <300 µg/L with transferrin saturation <20%) is treated with intravenous iron infusion (depending on the product available at the center). A restrictive transfusion strategy is recommended as long as the patient remains in the ICU, according to recent recommendations. Six visits are scheduled: V1 for inclusion and the first injection, V2 at Day 7(±2 days) for the second injection, V3 at Day 14(±2 days) for the third injection, V4 at Day 21(±2 days) for the fourth injection, V5 at Day 28(±2 days) for the fifth injection. | Drug | erythropoietin |
| PlaceboIn the control arm, patients receive a subcutaneous injection of placebo (0.9% NaCl) according to the same schedule. The study treatments are administered by an open-label nurse. In both groups, before each injection, iron deficiency (defined as reticulocyte Hb <29 pg, or hepcidin <41 µg/L, or ferritin <100 µg/L, or ferritin <300 µg/L with transferrin saturation <20%) is treated with intravenous iron infusion (depending on the product available at the center). A restrictive transfusion strategy is recommended as long as the patient remains in the ICU, according to recent recommendations. Six visits are scheduled: V1 for inclusion and the first injection, V2 at Day 7(±2 days) for the second injection, V3 at Day 14(±2 days) for the third injection, V4 at Day 21(±2 days) for the fourth injection, V5 at Day 28(±2 days) for the fifth injection. | Drug | Placebo |
Primary outcome
Recruitment rate
Time frame: 90 days
≥50% of eligible patients will need to be enrolled, but the trial will not be feasible if the inclusion rate is ≤ 25% or less
Adherence to allocation groups
Time frame: 90 days
A high level of matching of randomization and group allocation should be achieved, with at least 85% of included patients receiving protocol-allocated treatment, but if ≤ 65% patients receive protocol-allocated treatment, the trial is not feasible
Completion of follow-up of included patients
Time frame: 90 days
≥ 85% of patients should be followed through to the end of follow-up, but if <65% patients are followed through to the last visit, the protocol will not be feasible
15 secondary outcomes
The proportion of patients lost to follow-up at each visit
Time frame: 7, 14, 21, 28 and 90 days
The rate of missing data for mortality outcome
Time frame: 90 days
The rate of compliance with the therapeutic protocol at each visit for inpatients
Time frame: 7, 14, 21, and 28 days
Mean serum hemoglobin value
Time frame: 28 days
ICU mortality
Time frame: up to 90 days
Hospital mortality
Time frame: up to 90 days
ICU length of stay
Time frame: up to 90 days
Hospital length of stay
Time frame: up to 90 days
Blood transfusion
Time frame: 90 days
number of red blood cells transfused
Time frame: 90 days
90 days survival analysis
Time frame: 90 days
Occurrence of hospital readmission (censored at 90 days after inclusion),
Time frame: 90 days
Number of days living at home (or previous place of living)
Time frame: 90 days
Quality of life measured by the EQ-5D 5L scale, EuroQol 5 dimensions
Time frame: 90 days
Proportion of patients with a thromboembolic event
Time frame: 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2022.
- Individual participant dataSharing planned: Undecided. Yes
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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.
Maxime Léger, MD principal investigator
University Hospital, Angers
Sigismond Lasocki, MD study director
University Hospital, Angers
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Erythropoietin in people with Anemia and Intensive Care, run by University Hospital, Angers at 2 sites 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 5 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 10 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Recruitment rate (time frame: 90 days). The study lists 3 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 10 Oct 2022; AzTrials last refreshed its copy on 7 Nov 2026.