Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

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

5. oktober 2022 opdateret af: 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.

Studieoversigt

Status

Aktiv, ikke rekrutterende

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

42

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Frankrig
      • Cholet, Frankrig
        • Cholet Hospital
      • Tours, Frankrig
        • UH Tours

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Tredobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: erythropoietin
Erythropoietin alpha or theta 40,000 UI (1 ml) sc each week if Hb <12 g/dL (for maximum 5 weeks)
Medicin: 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 komparator: Placebo
saline sc injection (1 ml) each weeks if Hb <12 g/dL, for a maximum of 5 weeks,
Medicin: 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.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Recruitment rate
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
The proportion of patients lost to follow-up at each visit
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 28 days
Mean serum hemoglobin value
28 days
ICU mortality
Tidsramme: up to 90 days
ICU mortality
up to 90 days
Hospitalsdødelighed
Tidsramme: op til 90 dage
Hospitalsdødelighed
op til 90 dage
ICU length of stay
Tidsramme: up to 90 days
ICU length of stay
up to 90 days
Hospital length of stay
Tidsramme: up to 90 days
Hospital length of stay
up to 90 days
Blood transfusion
Tidsramme: 90 days
Proportion of patients who received at least one red blood cell transfusion
90 days
number of red blood cells transfused
Tidsramme: 90 days
number of red blood cells transfused
90 days
90 days survival analysis
Tidsramme: 90 days
90 days survival analysis
90 days
Occurrence of hospital readmission (censored at 90 days after inclusion),
Tidsramme: 90 days
at least one hospital readmission after the hospital discharge
90 days
Number of days living at home (or previous place of living)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 90 days
Thrombolic event: pulmonary embolism, venous or arterial thrombosis
90 days

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

University Hospital, Angers

Efterforskere

  • Studieleder: Sigismond Lasocki, MD, Angers University hospital

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

28. januar 2022

Primær færdiggørelse (Faktiske)

2. september 2022

Studieafslutning (Forventet)

31. december 2022

Datoer for studieregistrering

Først indsendt

20. september 2021

Først indsendt, der opfyldte QC-kriterier

1. oktober 2021

Først opslået (Faktiske)

15. oktober 2021

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

10. oktober 2022

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

5. oktober 2022

Sidst verificeret

1. september 2022

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • EPO-ICU-FS

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

Uafklaret

IPD-planbeskrivelse

Yes

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ingen

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Anæmi

Kliniske forsøg med Erythropoietin

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Madagascar

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner