High Dose of Erythropoietin Analogue After Cardiac Arrest

Study Overview
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Brief Summary
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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
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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).

Official Title
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High Dose of Erythropoietin Analogue After Cardiac Arrest: a Multicentre, Randomised, Controlled Trial (Epo-ACR-02 Trial)

Conditions
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Comatose Survivors of Cardiac Arrest

Intervention / Treatment
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* Drug: EPOETINE ALPHA
* Other: Control arm


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EPO<br>five injections maximum of 40000 UI EPO | Drug: EPOETINE ALPHA<br>* 5 injections of 40000 UI of EPO<br>|
| Active Comparator: Control<br>Classical take care | Other: Control arm<br>* Usual take care of cardiac arrest<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients reaching a CPC (cerebral performance category) level 1 in each group |  | at day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distribution of patients in CPC (cerebral performance category) scale |  | at day 30 and day 60 | 
| ICU, hospital D30 and D60 mortality |  | during hospitalization and at day 30 and day 60 | 
| All adverse events (including thrombotic events) |  | until day 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac arrest, erythropoietin, post-anoxic encephalopathy, neuroprotective drugs