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

NCT ID: NCT00878813

Last Updated: 2011-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

1102 participants

Study Classification

OBSERVATIONAL

Study Start Date

2009-03-31

Study Completion Date

2011-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Stroke Transient Ischemic Attack

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

1

All consecutive stroke patients undergoing acute intra-arterial revascularisation therapy

Sampling of 15ml blood

Intervention Type PROCEDURE

On admission, 2 x 7.5ml blood tubes will be drawn during the first routine blood sampling

Blood-Sampling

Intervention Type PROCEDURE

On day 1 after intra-arterial thrombolysis, 2 x 7.5ml blood tubes on the following routine blood-sampling will be drawn.

2

All consecutive stroke patients undergoing acute intra-venous revascularisation therapy

Sampling of 15ml blood

Intervention Type PROCEDURE

On admission, 2 x 7.5ml blood tubes will be drawn during the first routine blood sampling

Blood-Sampling

Intervention Type PROCEDURE

On day 1 after intra-arterial thrombolysis, 2 x 7.5ml blood tubes on the following routine blood-sampling will be drawn.

3

All consecutive stroke patients treated conservatively

Sampling of 15ml blood

Intervention Type PROCEDURE

On admission, 2 x 7.5ml blood tubes will be drawn during the first routine blood sampling

4

All consecutive TIA patients

Sampling of 15ml blood

Intervention Type PROCEDURE

On admission, 2 x 7.5ml blood tubes will be drawn during the first routine blood sampling

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Sampling of 15ml blood

On admission, 2 x 7.5ml blood tubes will be drawn during the first routine blood sampling

Intervention Type PROCEDURE

Blood-Sampling

On day 1 after intra-arterial thrombolysis, 2 x 7.5ml blood tubes on the following routine blood-sampling will be drawn.

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Basel

OTHER

Sponsor Role collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role collaborator

Goethe University

OTHER

Sponsor Role collaborator

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Gian Marco De Marchis, MD

Role: PRINCIPAL_INVESTIGATOR

Inselspital, Bern University Hospital

Marcel Arnold, MD

Role: PRINCIPAL_INVESTIGATOR

Inselspital, Bern University Hospital

Mira Katan, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Abteilung für Neurologie Charité - Campus Benjamin Franklin

Berlin, , Germany

Site Status

Goethe University

Frankfurt am Main, , Germany

Site Status

Neurologische Klinik, Universitätsspital Basel

Basel, , Switzerland

Site Status

University Clinic for Neurology, Bern University Hospital

Bern, , Switzerland

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Germany Switzerland

References

Explore related publications, articles, or registry entries linked to this study.

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. doi: 10.1001/jama.282.21.2003.

Reference Type BACKGROUND
PMID: 10591382 (View on PubMed)

Mattle HP, Arnold M, Georgiadis D, Baumann C, Nedeltchev K, Benninger D, Remonda L, von Budingen 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. doi: 10.1161/STROKEAHA.107.492348. Epub 2007 Dec 20.

Reference Type BACKGROUND
PMID: 18096842 (View on PubMed)

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. doi: 10.1212/01.wnl.0000145626.30318.8a.

Reference Type BACKGROUND
PMID: 15596765 (View on PubMed)

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. doi: 10.1046/j.1468-1331.2003.00749.x.

Reference Type BACKGROUND
PMID: 14692888 (View on PubMed)

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. doi: 10.1161/01.STR.0000144051.32131.09. Epub 2004 Oct 7.

Reference Type BACKGROUND
PMID: 15472105 (View on PubMed)

Rubiera M, Alvarez-Sabin 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. doi: 10.1161/01.STR.0000170711.43405.81. Epub 2005 Jun 9.

Reference Type BACKGROUND
PMID: 15947260 (View on PubMed)

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. doi: 10.1161/STROKEAHA.107.181486. Epub 2007 Apr 12.

Reference Type BACKGROUND
PMID: 17431204 (View on PubMed)

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. doi: 10.1159/000074818. No abstract available.

Reference Type BACKGROUND
PMID: 14707405 (View on PubMed)

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. doi: 10.1373/clinchem.2005.060038. Epub 2005 Nov 3.

Reference Type BACKGROUND
PMID: 16269513 (View on PubMed)

Katan M, Morgenthaler N, Widmer I, Puder JJ, Konig C, Muller 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.

Reference Type BACKGROUND
PMID: 18580851 (View on PubMed)

Rudin S, Kriemler L, Dittrich TD, Zietz A, Schweizer J, Arnold M, Peters N, Barinka F, Jung S, Arnold M, Fischer U, Rentsch K, Christ-Crain M, Katan M, De Marchis GM. Lipoprotein(a) as a blood marker for large artery atherosclerosis stroke etiology: validation in a prospective cohort from a swiss stroke center. Swiss Med Wkly. 2024 Apr 2;154:3633. doi: 10.57187/s.3633.

Reference Type DERIVED
PMID: 38579294 (View on PubMed)

De Marchis GM, Dankowski T, Konig IR, Fladt J, Fluri F, Gensicke H, Foerch C, Findling O, Kurmann R, Fischer U, Luft A, Buhl D, Engelter ST, Lyrer PA, Christ-Crain M, Arnold M, Katan M. A novel biomarker-based prognostic score in acute ischemic stroke: The CoRisk score. Neurology. 2019 Mar 26;92(13):e1517-e1525. doi: 10.1212/WNL.0000000000007177. Epub 2019 Mar 1.

Reference Type DERIVED
PMID: 30824558 (View on PubMed)

De Marchis GM, Weck A, Audebert H, Benik S, Foerch C, Buhl D, Schuetz P, Jung S, Seiler M, Morgenthaler NG, Mattle HP, Mueller B, Christ-Crain M, Arnold M, Katan M. Copeptin for the prediction of recurrent cerebrovascular events after transient ischemic attack: results from the CoRisk study. Stroke. 2014 Oct;45(10):2918-23. doi: 10.1161/STROKEAHA.114.005584. Epub 2014 Aug 28.

Reference Type DERIVED
PMID: 25169950 (View on PubMed)

De Marchis GM, Katan M, Weck A, Brekenfeld C, Mattle HP, Buhl D, Muller B, Christ-Crain M, Arnold M. Copeptin and risk stratification in patients with ischemic stroke and transient ischemic attack: the CoRisk study. Int J Stroke. 2013 Apr;8(3):214-8. doi: 10.1111/j.1747-4949.2011.00762.x. Epub 2012 Feb 15.

Reference Type DERIVED
PMID: 22336226 (View on PubMed)

Katan M, Elkind MS. Inflammatory and neuroendocrine biomarkers of prognosis after ischemic stroke. Expert Rev Neurother. 2011 Feb;11(2):225-39. doi: 10.1586/ern.10.200.

Reference Type DERIVED
PMID: 21306210 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

KEK 001/09

Identifier Type: -

Identifier Source: org_study_id