Erythropoietin to Improve Critical Care Patient Outcomes
- Conditions
- AnemiaIntensive Care
- Interventions
- Drug: Placebo
- Registration Number
- NCT05080049
- Lead Sponsor
- University Hospital, Angers
- Brief 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 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 42
- 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).
- 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,
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description erythropoietin Erythropoietin Erythropoietin alpha or theta 40,000 UI (1 ml) sc each week if Hb \<12 g/dL (for maximum 5 weeks) Placebo Placebo saline sc injection (1 ml) each weeks if Hb \<12 g/dL, for a maximum of 5 weeks,
- Primary Outcome Measures
Name Time Method Recruitment rate 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 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 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
- Secondary Outcome Measures
Name Time Method The proportion of patients lost to follow-up at each visit 7, 14, 21, 28 and 90 days The proportion of patients lost to follow-up at each visit
The rate of missing data for mortality outcome 90 days The rate of missing data for mortality outcome
Mean serum hemoglobin value 28 days Mean serum hemoglobin value
ICU mortality up to 90 days ICU mortality
Hospital mortality up to 90 days Hospital mortality
Hospital length of stay up to 90 days Hospital length of stay
The rate of compliance with the therapeutic protocol at each visit for inpatients 7, 14, 21, and 28 days The rate of compliance with the therapeutic protocol at each visit for inpatients
ICU length of stay up to 90 days ICU length of stay
Blood transfusion 90 days Proportion of patients who received at least one red blood cell transfusion
number of red blood cells transfused 90 days number of red blood cells transfused
90 days survival analysis 90 days 90 days survival analysis
Occurrence of hospital readmission (censored at 90 days after inclusion), 90 days at least one hospital readmission after the hospital discharge
Number of days living at home (or previous place of living) 90 days Number of days living at home (or previous place of living) at D90
Quality of life measured by the EQ-5D 5L scale, EuroQol 5 dimensions 90 days 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.
Proportion of patients with a thromboembolic event 90 days Thrombolic event: pulmonary embolism, venous or arterial thrombosis
Trial Locations
- Locations (2)
Cholet Hospital
🇫🇷Cholet, France
UH Tours
🇫🇷Tours, France