PROgnostic Value of MicroParticles and Markers of Hemostasis in TIA and Ischemic Stroke

Brain Ischemia Clinical Trial

— PROMPTS  

Official title:

PROgnostic Value of MicroParticles and Markers of Hemostasis in TIA and Ischemic Stroke

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05524506
• Other study ID #: KIDS-IM-LL-2016-01
• Status: Completed
• Start date: June 2007
• Est. completion date: June 30, 2021

Study information

• Verified date: August 2022
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose is to investigate if different microparticles and markers of hemostasis predict outcome after TIA or ischemic stroke and to study the association between these variables and stroke subtype or etiology.

Description:

1. Introduction Within a previous study ('PROPPSTOPP') a cohort of 249 patients with ischemic stroke (IS) or TIA was established in Stockholm between 2007 and 2009. The original aims were twofold: 1) to look for occult atrial fibrillation (completed, NTC01160406) and 2) to investigate microparticle levels and markers of hemostasis in the acute phase and one month after symptoms. Blood samples were taken on both occasions. Patients were found to have higher microparticle levels and increased thrombin generation in plasma both acutely and at one month as compared to healthy controls.

This follow-up study will investigate the prognostic ability of microparticles (primary variables) and markers of hemostasis (secondary variables) to predict outcome as documented in hospital records and Swedish registers. The association between microparticles/coagulation markers and stroke subtype/etiology will also be investigated.

2. Variables

2.1 Microparticles

Microparticles are membrane vesicles (0.1-1.0 µm) released from cells at activation or apoptosis. They carry surface markers from the releasing cell. Microparticles are of interest as biomarkers for activation of cells in the circulation, e g platelets, endothelial cells or leukocytes. They may have pro-coagulant properties. For this study the following microparticles and surface markers have been analyzed:

• Total number of microparticles (MP's)

• Number of MP's exposing phosphatidylserine (PS) (pro-coagulant property)

• Number of MP's of any type exposing tissue factor (TF), with or without simultaneous exposure of PS (pro-coagulant properties, activation of monocytes/endothelium)

• Number of platelet microparticles (PMP's), identified by surface exposure of GPαIIb (CD41), with or without simultaneous exposure of PS (platelet activation)

• Number of PMP's exposing P-selectin with or without simultaneous exposure of PS (platelet activation)

• Number of PMP's exposing TF with or without simultaneous exposure of PS (pro-coagulant properties)

2.2 Markers of hemostasis

Different variables of importance for coagulation, platelet activation, fibrinolysis and inflammation were measured in the original study, namely:

• Prothrombin fragment F1+2

• Thrombin generation by Calibrated Automated Thrombin generation (CAT)

• Microparticle-pellet induced thrombin generation

3. Outcome

3.1 Primary outcome

The primary outcome is new ischemic events, i e fatal or non-fatal recurrent ischemic stroke, myocardial infarction or ischemic cardiovascular death in the time frame 2007-2014. Diagnoses will be retrieved from the following sources:

• The Swedish Register for Cause of death

• The Swedish Register of in-house hospital care

• Medical records at recruiting hospitals.

3.2 Secondary outcome

Secondary outcomes are recurrent ischemic stroke respectively all-cause mortalitý as documented in the sources above.

4. Statistical Methods

The statistical analysis of the prospective cohort study will be performed in steps:

1. Descriptive statistics comparing averages/medians of the above variables for patients with and without outcome.

2. For variables with p-values < 0.2 in step 1: univariate event-free survival Kaplan-Meyer curves by variable median split. Probability calculations of differences by log-rank test.

3. Multivariate analysis by Cox regression analysis including the most significant variables in step 2 and established cardiovascular risk factors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 249
• Est. completion date: June 30, 2021
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 45 Years and older

Eligibility

Cohort established in NTC01160406

Inclusion Criteria:

• acute ischemic stroke or TIA less than 2 weeks before enrollment

• ability to understand study instructions both verbal and written

• ability to handle handheld ECG

Exclusion Criteria:

• known atrial fibrillation

• hemorrhagic stroke at time of enrollment

• limited compliance

• pacemaker

Related Conditions & MeSH terms

• Brain Ischemia
• Cerebral Infarction
• Cerebral Ischemia
• Extracellular Vesicles
• Hemostasis
• Ischemia
• Ischemic Stroke
• Prognosis

Locations

Country	Name	City	State
Sweden	Karolinska Institutet, Daderyd Hospital	Stockholm

Sponsors (3)

Lead Sponsor	Collaborator
Karolinska Institutet	Danderyd Hospital, Stockholm South General Hospital

Country where clinical trial is conducted

Sweden, 

References & Publications (2)

Lundström A, Änggårdh-Rooth E, Mobarrez F, Thålin C, Gigante B, Laska AC, Wallén H. High Thrombin Generation after Acute Ischemic Stroke or Transient Ischemic Attack Is Associated with a Reduced Risk of Recurrence: An Observational Cohort Study. Thromb Haemost. 2021 May;121(5):584-593. doi: 10.1055/s-0040-1721146. Epub 2020 Dec 12. — View Citation

Lundström A, Mobarrez F, Rooth E, Thålin C, von Arbin M, Henriksson P, Gigante B, Laska AC, Wallén H. Prognostic Value of Circulating Microvesicle Subpopulations in Ischemic Stroke and TIA. Transl Stroke Res. 2020 Aug;11(4):708-719. doi: 10.1007/s12975-019-00777-w. Epub 2020 Jan 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fatal or non-fatal ischemic stroke or myocardial infarction.	New fatal or non-fatal ischemic stroke after the initial ischemic stroke or TIA leading to recruitment. Outcome events and time of events are extracted from national registries ('Patientregistret', 'Dödsorsaksregistret') and hospital records.	2007-2014
Secondary	Recurrent ischemic stroke	Recurrent ischemic stroke (fatal or non-fatal) after initial ischemic stroke or TIA leading to recruitment. Outcome events and time of events are extracted from national registries ('Patientregistret') and hospital records.	2007-2014
Secondary	All-cause mortality	All cause mortality after initial ischemic stroke or TIA leading to recruitment. Outcome events and time of events are extracted from national registry ('Dödsorsaksregistret').	2007-2014