Clinical trial NCT00878813: Copeptin for Risk Stratification in Acute Stroke Patients: the CoRisk Study
Official title: Copeptin for Risk Stratification in Acute Stroke Patients: the CoRisk-study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Stroke
Transient Ischemic Attack
Keywords: Copeptin
Vasopressin
Stroke
Transient ischemic attack
Thrombolytic therapy
Prognosis
Complications
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: University of Basel
name: Charite University, Berlin, Germany
name: Goethe University
First posted: 2009-04-09
Enrollment: 1102
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All consecutive patients who are admitted to the emergency department of the Inselspital Bern - Switzerland with a clinical diagnosis of acute ischemic stroke within 24 hours of symptom onset. Inselspital Bern is a university based hospital with a catchment area of about 1.000.000 people

Brief summary: Prospective observational multicenter study to evaluate copeptin as a prognostic marker in patients with an acute cerebrovascular event. It includes four groups of patients, mainly depending on type of initial therapy (intra-arterial thrombolysis, intravenous thrombolysis, conservative treatment, TIA). The study takes place at the Emergency and neurological Department of the University of Bern, Switzerland; Department of Neurology, Goethe University of Frankfurt a.M. (Germany). Further participating centers are under discussion

Detailed description: Background

The investigators in the Prolyse in Acute Cerebral Thromboembolism (PROACT) II study found that intra-arterial thrombolysis (IAT) with prourokinase within 6 hours after onset of symptoms was beneficial in patients with middle cerebral artery (MCA) occlusion. Intra-arterial thrombolysis (IAT) thus is an option for treatment of selected patients who have major stroke of \<6 hours' duration due to occlusions of the MCA. Recently observational study showed that IAT was more beneficial than intra-venous thrombolysis (IVT) in the specific group of stroke patients presenting with hyperdense middle cerebral artery sign on CT, even though IAT was started later.

However complications after both reperfusion treatment modalities such as symptomatic intracerebral hemorrhage, malignant brain oedema, re-occlusion, infection, and seizures may occur. Unfortunately few clinical signs provide prognostic information for clear risk stratification. The guidelines for reperfusion therapies in Switzerland, Europe and the US do not include -for the time being- biomarkers in the decision-making-process. However there might be powerful biomarkers, which can serve as point of care tools for the risk stratification of candidates to receive thrombolysis. Plasma copeptin concentration has recently been shown to be an easy to determine, steady parameter which independently predicts functional outcome and death in patients with an acute ischemic stroke. Copeptin derives from a larger precursor peptide (pre-provasopressin) along with two other peptides, Vasopressin (AVP) and neurophysin II. Released in an equimolar ratio, the amount of copeptin mirrors the production of AVP. AVP plays an important role in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis and, thus, reflecting the individual stress response. "Stressors" such as stroke are strong stimulators of the release of AVP. The close and reproducible relation of copeptin levels to the degree of activation of the stress axis is the basis of its usefulness as a biomarker. Early prognostic factors to predict mortality and outcome in stroke patients are important to guide and tailor early decision on treatment. In this context, copeptin may be helpful tool in the early risk stratification of stroke patients to guide the decision for reperfusion therapies.

Objective

To evaluate copeptin as prognostic tool to predict outcome in a well-defined cohort of stroke patients.

Methods

Step 1. All eligible patients in the emergency department or the neurological ward will be evaluated for enrollment into the study. On admission, 2 x 7.5ml- EDTA-blood tubes will be drawn during the first routine blood sampling, and 2 x 7.5ml-EDTA-blood tubes on the following routine blood-sampling. Copeptin levels will be assessed in a blinded batch analysis upon completion of the plasma asservation. Measurement will be performed with a new chemiluminescence sandwich immunoassay.

Step 2. All baseline data will be collected. CT or MRI will be performed 22 to 36 hours after IAT. All complications including death after the reperfusion therapies will be assessed until discharge.

Step 3. A telephone follow-up regarding morbidity and mortality will be obtained after 3 months. An unfavorable outcome will be defined as a mRs of 3 to 6

Eligibility criteria: Inclusion Criteria:

All consecutive patients who are admitted to the emergency department with a clinical diagnosis of cerebrovascular event (TIA, stroke) within 24 hours of symptom onset

Exclusion Criteria:

Patients without informed consent. Patients discharged with a diagnosis different from stroke or TIA after diagnostic evaluation.

Primary outcomes:
measure: Major disability or death
timeFrame: 90 days after qualifying event
Secondary outcomes:
measure: Symptomatic intracranial hemorrhage
timeFrame: until hospital discharge
measure: Malignant brain oedema
timeFrame: until hospital discharge
measure: Aspiration pneumonia
timeFrame: until hospital discharge
measure: Seizure
timeFrame: until hospital discharge
measure: Mortality
timeFrame: until hospital discharge
measure: severe cerebrovascular re-event (i.e. new TIA, and stroke)
timeFrame: 90 days after qualifying event
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Abteilung für Neurologie Charité - Campus Benjamin Franklin
city: Frankfurt am Main
country: Germany
facility: Goethe University
city: Basel
country: Switzerland
facility: Neurologische Klinik, Universitätsspital Basel
city: Bern
country: Switzerland
facility: University Clinic for Neurology, Bern University Hospital
Study officials:
affiliation: Inselspital, Bern University Hospital
name: Gian Marco De Marchis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inselspital, Bern University Hospital
name: Marcel Arnold, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Basel, Switzerland
name: Mira Katan, MD
role: PRINCIPAL_INVESTIGATOR
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