Clinical trial NCT00999583: High Dose of Erythropoietin Analogue After Cardiac Arrest
Official title: High Dose of Erythropoietin Analogue After Cardiac Arrest: a Multicentre, Randomised, Controlled Trial (Epo-ACR-02 Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Comatose Survivors of Cardiac Arrest
Keywords: Cardiac arrest
erythropoietin
post-anoxic encephalopathy
neuroprotective drugs
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2009-10-22
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators hypothesised that the neuroprotective effects of erythropoietin and its analogues could lead to an improve outcome after cardiac arrest. To test this hypotheses, the investigators designed a randomized, multicentre, simple blind trial in which all participating patients will be receive usual treatments and 50% of them will also receive a high dose of epoetin alpha (an analogue of erythropoietin) in an "add on" fashion. The main end point will be the proportion of patients in each arm who will reach at day 60 the best level of recovery, using a 5 level score.

Detailed description: Rationale:

A recent pilot study showed encouraging results regarding the potentially beneficial effects of high dose epoetin alpha (an analogue of erythropoietin) when administered early after cardiac arrest. In this open label and non randomized trial, a high proportion of patients survived without significant cerebral disability and without experiencing severe adverse events (CARIOU et al. Resuscitation 2008). Efficiency of this treatment should now be evaluated in a randomized trial.

Hypotheses:

An early administration of a high dose of epoetin alpha (Epo) after cardiac arrest resuscitation could improve the neurological outcome of these patients by comparison with standard treatment. The proportion of patients reaching the level 1 of the Pittsburgh CPC scale (i.e., no or minor cerebral disability) at day 60 could attain 45% in the interventional group versus 30% as expected in the control group.

Design:

Multicentre, randomised, controlled, simple blind trial ("add on study").

Main goal:

To test the efficiency of a high dose of Epo administered at the early stage of the post-cardiac arrest period regarding its ability to improve the neurological outcome of these patients, when compared with standard care (including hypothermia when indicated).

Eligibility criteria: Inclusion criteria:

* Age between 18 and 80
* Witnessed out-of-hospital cardiac arrest, presumed of cardiac origin (non asphyxic)
* Time from cardiac arrest and recovery of circulatory activity less than 60 minutes
* Persistent coma after ROSC (Coma Glasgow Scale \< 7)

Exclusion criteria:

* Out-of-hospital cardiac arrest with evidence of extra-cardiac cause (trauma, sepsis, acute respiratory insufficiency, asphyxia)
* Previous or chronic treatment with erythropoietin or analogues
* Pregnancy
* Rapidly fatal underlying disease (expected life duration \< 6 months)
* No social security

Primary outcomes:
measure: Number of patients reaching a CPC (cerebral performance category) level 1 in each group
timeFrame: at day 60
Secondary outcomes:
measure: Distribution of patients in CPC (cerebral performance category) scale
timeFrame: at day 30 and day 60
measure: ICU, hospital D30 and D60 mortality
timeFrame: during hospitalization and at day 30 and day 60
measure: All adverse events (including thrombotic events)
timeFrame: until day 60
Other outcomes:
Locations:
city: Paris
country: France
facility: Medical intensive care unit of Cochin-St Vincent de Paul university Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Alain Cariou, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Madelaine T, Cour M, Roy P, Vivien B, Charpentier J, Dumas F, Deye N, Bonnefoy E, Gueugniaud PY, Coste J, Cariou A, Argaud L. Prediction of Brain Death After Out-of-Hospital Cardiac Arrest: Development and Validation of the Brain Death After Cardiac Arrest Score. Chest. 2021 Jul;160(1):139-147. doi: 10.1016/j.chest.2021.01.056. Epub 2021 Jun 8.
citation: Boissady E, Kohlhauer M, Lidouren F, Hocini H, Lefebvre C, Chateau-Jouber S, Mongardon N, Deye N, Cariou A, Micheau P, Ghaleh B, Tissier R. Ultrafast Hypothermia Selectively Mitigates the Early Humoral Response After Cardiac Arrest. J Am Heart Assoc. 2020 Dec;9(23):e017413. doi: 10.1161/JAHA.120.017413. Epub 2020 Nov 17.
citation: Cariou A, Deye N, Vivien B, Richard O, Pichon N, Bourg A, Huet L, Buleon C, Frey J, Asfar P, Legriel S, Narcisse S, Mathonnet A, Cravoisy A, Dequin PF, Wiel E, Razazi K, Daubin C, Kimmoun A, Lamhaut L, Marx JS, de la Garanderie DP, Ecollan P, Combes A, Spaulding C, Barat F, Ben Boutieb M, Coste J, Chiche JD, Pene F, Mira JP, Treluyer JM, Hermine O, Carli P; Epo-ACR-02 Study Group. Early High-Dose Erythropoietin Therapy After Out-of-Hospital Cardiac Arrest: A Multicenter, Randomized Controlled Trial. J Am Coll Cardiol. 2016 Jul 5;68(1):40-9. doi: 10.1016/j.jacc.2016.04.040.