Copeptin for Risk Stratification in Acute Stroke Patients: the CoRisk Study

Stroke Clinical Trial

— CoRisk  

Official title:

Copeptin for Risk Stratification in Acute Stroke Patients: the CoRisk-study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00878813
• Other study ID #: KEK 001/09
• Status: Completed
• Phase: N/A
• First received: April 1, 2009
• Last updated: November 9, 2011
• Start date: March 2009
• Est. completion date: October 2011

Study information

• Verified date: November 2011
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Ethikkommission
• Study type: Observational

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1102
• Est. completion date: October 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Ischemic Attack, Transient
• Stroke
• Transient Ischemic Attack

Intervention

Procedure:
• Sampling of 15ml blood
On admission, 2 x 7.5ml blood tubes will be drawn during the first routine blood sampling
• Blood-Sampling
On day 1 after intra-arterial thrombolysis, 2 x 7.5ml blood tubes on the following routine blood-sampling will be drawn.

Locations

Country	Name	City	State
Germany	Abteilung für Neurologie Charité - Campus Benjamin Franklin	Berlin
Germany	Goethe University	Frankfurt am Main
Switzerland	Neurologische Klinik, Universitätsspital Basel	Basel
Switzerland	University Clinic for Neurology, Bern University Hospital	Bern

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne	Charite University, Berlin, Germany, Goethe University, University of Basel

Countries where clinical trial is conducted

Germany,  Switzerland, 

References & Publications (10)

Adams HP Jr, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, Grubb RL, Higashida RT, Jauch EC, Kidwell C, Lyden PD, Morgenstern LB, Qureshi AI, Rosenwasser RH, Scott PA, Wijdicks EF; American Heart Association; American Stroke Association Stroke Council; Clinical Cardiology Council; Cardiovascular Radiology and Intervention Council; Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 2007 May;38(5):1655-711. Epub 2007 Apr 12. Erratum in: Stroke. 2007 Jun;38(6):e38. Stroke. 2007 Sep;38(9):e96. — View Citation

Aslanyan S, Weir CJ, Diener HC, Kaste M, Lees KR; GAIN International Steering Committee and Investigators. Pneumonia and urinary tract infection after acute ischaemic stroke: a tertiary analysis of the GAIN International trial. Eur J Neurol. 2004 Jan;11(1):49-53. — View Citation

Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, Pessin M, Ahuja A, Callahan F, Clark WM, Silver F, Rivera F. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA. 1999 Dec 1;282(21):2003-11. — View Citation

Katan M, Morgenthaler N, Widmer I, Puder JJ, König C, Müller B, Christ-Crain M. Copeptin, a stable peptide derived from the vasopressin precursor, correlates with the individual stress level. Neuro Endocrinol Lett. 2008 Jun;29(3):341-6. — View Citation

Maramattom BV, Bahn MM, Wijdicks EF. Which patient fares worse after early deterioration due to swelling from hemispheric stroke? Neurology. 2004 Dec 14;63(11):2142-5. Review. — View Citation

Mattle HP, Arnold M, Georgiadis D, Baumann C, Nedeltchev K, Benninger D, Remonda L, von Büdingen C, Diana A, Pangalu A, Schroth G, Baumgartner RW. Comparison of intraarterial and intravenous thrombolysis for ischemic stroke with hyperdense middle cerebral artery sign. Stroke. 2008 Feb;39(2):379-83. Epub 2007 Dec 20. — View Citation

Morgenthaler NG, Struck J, Alonso C, Bergmann A. Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem. 2006 Jan;52(1):112-9. Epub 2005 Nov 3. — View Citation

Rubiera M, Alvarez-Sabín J, Ribo M, Montaner J, Santamarina E, Arenillas JF, Huertas R, Delgado P, Purroy F, Molina CA. Predictors of early arterial reocclusion after tissue plasminogen activator-induced recanalization in acute ischemic stroke. Stroke. 2005 Jul;36(7):1452-6. Epub 2005 Jun 9. — View Citation

Toni D, Chamorro A, Kaste M, Lees K, Wahlgren NG, Hacke W; EUSI Executive Committee; EUSI Writing Committee. Acute treatment of ischaemic stroke. European Stroke Initiative. Cerebrovasc Dis. 2004;17 Suppl 2:30-46. — View Citation

Warach S, Latour LL. Evidence of reperfusion injury, exacerbated by thrombolytic therapy, in human focal brain ischemia using a novel imaging marker of early blood-brain barrier disruption. Stroke. 2004 Nov;35(11 Suppl 1):2659-61. Epub 2004 Oct 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major disability or death		90 days after qualifying event	No
Secondary	Symptomatic intracranial hemorrhage		until hospital discharge	No
Secondary	Malignant brain oedema		until hospital discharge	No
Secondary	Aspiration pneumonia		until hospital discharge	No
Secondary	Seizure		until hospital discharge	No
Secondary	Mortality		until hospital discharge	No
Secondary	severe cerebrovascular re-event (i.e. new TIA, and stroke)		90 days after qualifying event	No