Observational Dutch Young Symptomatic StrokE studY - nEXT

Cardiovascular Diseases Clinical Trial

— ODYSSEY-nEXT  

Official title:

Observational Dutch Young Symptomatic StrokE studY - Extended

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05853796
• Other study ID #: NL77518.091.21
• Status: Recruiting
• Start date: February 6, 2023
• Est. completion date: January 1, 2037

Study information

• Verified date: May 2023
• Source: Radboud University Medical Center
• Contact: Frank-Erik De Leeuw, Prof.
• Phone: 0031650200314
• Email: frankerik.deleeuw[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

BACKGROUND: Worldwide, 2 million patients aged 18-50 years suffer an ischemic stroke each year with an increasing trend over the past decade due to yet unknown reasons. Whereas prognosis and antithrombotic treatment in older patients with cardiovascular disease are among the best studied topics in clinical medicine, this does not hold true for patients at young age. It is of great importance to treat these patient groups correctly to prevent recurrence and bleeding complications. However, previous research have shown that there is a long-term increased risk of recurrent ischemic events despite the secondary prevention and a subsequent increased bleeding risk. To tailor effective antithrombotic therapy to the individual patient, it is essential to understand the underlying pathogenesis and identify modifiable risk factors in young patients for recurrence or bleeding. It is thought that abnormalities of hemostasis may play a key role in early-onset ischemic stroke. First, prothrombotic conditions are associated with an increased risk for ischemic stroke at young age. In addition, disturbance of the hemostatic balance due to one or several triggers can activate the coagulation cascade, which on its turn can lead or contribute to clot formation and subsequent arterial occlusion. In previous study, there were indications that trigger factors such as fever and/or an infection in the days prior to the stroke may play a role in the pathogenesis. This suggests that an interaction between inflammation, endothelial damage and coagulation may lead to the formation of a clot. In this observational study we aim to investigate the role of the immune system, endothelial damage and coagulation in the pathogenesis and prognosis of stroke in young patients.

OBJECTIVE: To investigate the role of hemostasis, inflammation and endothelial activation in the etiology and prognosis in an acute ischemic stroke (or TIA) in young stroke patients.

STUDY DESIGN: Multicentre prospective observational study

STUDY POPULATION:

All patients aged between 18 and 50 years old with a first-ever ischemic stroke or TIA who are admitted to the neurology ward or seen at the outpatient clinic of one of the participating centers.

Main exclusion criteria are: history of clinical TIA, ischemic stroke or intracerebral hemorrhage. A intracerebral hemorrhage resulting from trauma, known aneurysm or underlying intracerebral malignancy. A venous infarction, retinal infarction and amourosis fugax. Inadequate control of the Dutch language to reliably sign an informed consent from and/or participate in the follow-up. Patients are excluded if they have a contra indication for 3T MRI.

In addition 60 healthy controls (18-50 years old) will be included.

MAIN STUDY ENDPOINTS:

1. Baseline and 3 months coagulation profile:

Whole blood and platelet poor plasma thrombin generation, platelet function tests, and coagulation biomarkers, screening for thrombophilia.

2. Baseline and 3 months inflammation/endothelial activation profile:

Cytokines/chemokines, expression of receptors/cofactors related to hemostasis on peripheral blood mononuclear cells (PBMCs), stimulation tests of PBMC's to assess trained immunity.

3. Vessel wall enhancement on 3 Tesla MRI

4. Questionnaire trigger factors

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 280
• Est. completion date: January 1, 2037
• Est. primary completion date: January 1, 2027
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Patients with a first-ever transient ischemic attack (TIA) or acute ischemic stroke aged between 18 and 50 years old

• For this study, acute stroke is defined as "occurence of acute neurological deficit lasting more than 24 hours, with confirmation on imaging (CT(-a) or MR(-a))".TIA is defined as "occurence of acute neurological deficit lasting less than 24 hours with confirmation of ischemia on MRI).

• Patients have a kidney function eGFR>30ml/min.

Exclusion Criteria:

• A history of clinical TIA, ischemic stroke or intracerebral hemorrhage

• A intracerebral hemorrhage resulting from trauma, known aneurysm or underlying intracerebral malignancy.

• A venous infarction, retinal infarction or amourosis fugax.

• Inadequate control of the Dutch language to reliably sign an informed consent from and/or participate in the follow-up

• Patients are excluded if they have a contra indication for 3T MRI.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Cerebrovascular Disorders
• Coagulation
• Embolism
• Embolism and Thrombosis
• Ischemic Stroke
• Stroke
• Thrombophilia
• Thrombosis

Locations

Country	Name	City	State
Netherlands	HagaZiekenhuis	Den Haag	Zuid-Holland
Netherlands	Catharina Ziekenhuis	Eindhoven	Noord-Brabant
Netherlands	Medisch Spectrum Twente	Enschede	Overijssel
Netherlands	Medisch Centrum Leeuwarden	Leeuwarden
Netherlands	Radboudumc	Nijmegen	Gelderland
Netherlands	Isala	Zwolle	Overijssel

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University Medical Center	Synapse bv

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Modified Rankin Scale	Functional outcome will be assessed with modified Rankin Scale	at 3-month visit and at annual follow-up contacts from year 1 to year 10
Other	Functional outcome will be assessed with Barthel Index		at 3-month visit and at annual follow-up contacts from year 1 to year 10.
Other	Coping strategies	Questionnaire about different strategies to cope with major setbacks.	at 3 months visit and 6 months
Other	Subjective cognitive outcome	Subjective cognition will be assessed with an electronic questionnaire	at 6-month follow-up
Primary	Difference of concentration biomarkers and coagulation assays between patients and controls	Biomarkers and assays of coagulation, inflammation and endothelium activation	At baseline and 3 month visit
Secondary	Nonfatal or fatal recurrent cardiovascular (ischemic) events	Ischemic stroke or transient ischemic attack, acute coronary syndrome, peripheral artery disease	10 years
Secondary	Recurrent venous thrombotic events	Deep venous thrombosis, pulmonary embolism, cerebral venous sinus thrombosis	10 years
Secondary	Death from any cause		10 years
Secondary	Malignancy		10 years
Secondary	Bleeding complications	Minor and major bleeding complications	10 years
Secondary	Vessel wall imaging on 3T MRI	Detection of vessel wall enhancement on MRI in young stroke patients	At baseline