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Erythropoietin to Improve Critical Care Patient Outcomes (EPO-ICU-FS)

5 oktober 2022 uppdaterad av: University Hospital, Angers

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.

Studieöversikt

Status

Aktiv, inte rekryterande

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

42

Fas

  • Fas 3

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Frankrike
      • Cholet, Frankrike
        • Cholet Hospital
      • Tours, Frankrike
        • UH Tours

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Trippel

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: erythropoietin
Erythropoietin alpha or theta 40,000 UI (1 ml) sc each week if Hb <12 g/dL (for maximum 5 weeks)
Läkemedel: Erythropoietin

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.
Placebo-jämförare: Placebo
saline sc injection (1 ml) each weeks if Hb <12 g/dL, for a maximum of 5 weeks,
Läkemedel: Placebo

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.

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Recruitment rate
Tidsram: 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
90 days
Adherence to allocation groups
Tidsram: 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
90 days
Completion of follow-up of included patients
Tidsram: 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
90 days

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
The proportion of patients lost to follow-up at each visit
Tidsram: 7, 14, 21, 28 and 90 days
The proportion of patients lost to follow-up at each visit
7, 14, 21, 28 and 90 days
The rate of missing data for mortality outcome
Tidsram: 90 days
The rate of missing data for mortality outcome
90 days
The rate of compliance with the therapeutic protocol at each visit for inpatients
Tidsram: 7, 14, 21, and 28 days
The rate of compliance with the therapeutic protocol at each visit for inpatients
7, 14, 21, and 28 days
Mean serum hemoglobin value
Tidsram: 28 days
Mean serum hemoglobin value
28 days
ICU mortality
Tidsram: up to 90 days
ICU mortality
up to 90 days
Sjukhusdödlighet
Tidsram: upp till 90 dagar
Sjukhusdödlighet
upp till 90 dagar
ICU length of stay
Tidsram: up to 90 days
ICU length of stay
up to 90 days
Hospital length of stay
Tidsram: up to 90 days
Hospital length of stay
up to 90 days
Blood transfusion
Tidsram: 90 days
Proportion of patients who received at least one red blood cell transfusion
90 days
number of red blood cells transfused
Tidsram: 90 days
number of red blood cells transfused
90 days
90 days survival analysis
Tidsram: 90 days
90 days survival analysis
90 days
Occurrence of hospital readmission (censored at 90 days after inclusion),
Tidsram: 90 days
at least one hospital readmission after the hospital discharge
90 days
Number of days living at home (or previous place of living)
Tidsram: 90 days
Number of days living at home (or previous place of living) at D90
90 days
Quality of life measured by the EQ-5D 5L scale, EuroQol 5 dimensions
Tidsram: 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.
90 days
Proportion of patients with a thromboembolic event
Tidsram: 90 days
Thrombolic event: pulmonary embolism, venous or arterial thrombosis
90 days

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

University Hospital, Angers

Utredare

  • Studierektor: Sigismond Lasocki, MD, Angers University hospital

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

28 januari 2022

Primärt slutförande (Faktisk)

2 september 2022

Avslutad studie (Förväntat)

31 december 2022

Studieregistreringsdatum

Först inskickad

20 september 2021

Först inskickad som uppfyllde QC-kriterierna

1 oktober 2021

Första postat (Faktisk)

15 oktober 2021

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

10 oktober 2022

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

5 oktober 2022

Senast verifierad

1 september 2022

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • EPO-ICU-FS

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

Obeslutsam

IPD-planbeskrivning

Yes

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Nej

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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