Neutrophil Extracellular Traps and Thrombolysis in the Acute Stroke

Acute Stroke Clinical Trial

— NETs  

Official title:

Neutrophil Extracellular Traps and Thrombolysis in the Acute Stroke

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02476188
• Other study ID #: D15-P007
• Status: Completed
• Phase: N/A
• First received: June 11, 2015
• Last updated: October 18, 2017
• Start date: July 31, 2015
• Est. completion date: November 2016

Study information

• Verified date: October 2017
• Source: Centre Hospitalier St Anne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study was to investigate the correlation between the nucleosome concentration and the rate of recanalization after thrombolysis. All patients were admitted to the Stroke Unit at the University Hospital Sainte-Anne where they received standard stroke care. The investigators included all patients treated or not by intravenous thrombolysis for anterior circulation stroke with or without vessel occlusion. Exclusion criteria were neoplasms, chronic inflammatory diseases and cytostatic therapy at the time of stroke and stroke-specifics symptoms that had started earlier than 4.5 hours before admission.

Description:

Neutrophil extracellular traps (NETs) were measured in serum at the time of hospitalization, then at 4 hours, 24 hours and 72 hours after stroke. Because of nucleosome instability, a strict preanalytical protocol was followed. Blood samples were centrifuged within 1-2 h after blood drawing. A strict preanalytical protocol was followed including early centrifugation of the samples and storage at - 80°C. NETs were quantified in batches containing all samples from a patient using the detection of MPO (myeloperoxidase) then the Cell-Death-Detection ELISAPLUS (Roche Diagnostics, Germany) as described earlier. Nucleosomes were quantified in relative arbitrary units (AU). Blood samples from each patient were measured within the same run to improve the comparability of the results.

For statistical analysis, various variables of nucleosomes were considered, such as the absolute concentrations determined at admission, at 24 hours and at 72 hours after stroke. Influence of nucleosome concentration on recanalization was tested. Continuous correlations of nucleosomes and infarction volume, nucleosomes and clot size, as well as of infarction volume and NIHSS were calculated by Spearman's rank correlation together with the 95% confidence interval. A p value < 0.05 was considered statistically significant.

The extent of the morphological damage was determined at time of admission to the hospital and 24 hours after thrombolysis by diffusion-weighted magnetic resonance imaging (MRI). The pretreat¬ment and follow-up DWI lesions was segmented using interactive tools based on DWI signal intensity thresholding within a 3-dimensional mask encompassing the apparent area of bright DWI signal intensity and morphometric filtering. The clot location and length were assessed on the susceptibility vessel sign on T2* as describe earlier.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: November 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients ("Patients" + "Patients control" groups) :

Inclusion-1st sample of blood : every patient recruited within the neurovascular unit of intensive care of the Hospital center Sainte - Anne within the framework of a "thrombolyse alert ".

Then pursuit of the study ("patients" group only) if :

• Age 18 minimum

• Sylvien Infarct proved by the intellectual MRI,

• Whatever is the treatment received (Aspegic, thombolysis and/or thrombectomy)

• That there is occlusion of a cerebral artery or not "Controls" group :

• Healthy subjects,

• Mated on the age and the vascular risk factors (tobacco, arterial high blood pressure, diabetes and dyslipidémie)

Exclusion Criteria:

• Patients:

• Contraindications in the intravenous thrombolysis according to the current recommendations .

• Controls:

• Histories of evolutionary pathology or thrombo-embolique, taken by treatment whatever it is except contraceptive for the women, the viral or bacterial infection in the month precedents

Related Conditions & MeSH terms

• Acute Stroke
• Stroke

Intervention

Procedure:
• Sample of Blood

Locations

Country	Name	City	State
France	Centre Hospitalier Sainte-Anne	Paris

Sponsors (3)

Lead Sponsor	Collaborator
Centre Hospitalier St Anne	Institut National de la Santé Et de la Recherche Médicale, France, University of Paris 5 - Rene Descartes

Country where clinical trial is conducted

France, 

References & Publications (3)

Holdenrieder S, Stieber P, Bodenmüller H, Fertig G, Fürst H, Schmeller N, Untch M, Seidel D. Nucleosomes in serum as a marker for cell death. Clin Chem Lab Med. 2001 Jul;39(7):596-605. — View Citation

Holdenrieder S, Stieber P, Chan LY, Geiger S, Kremer A, Nagel D, Lo YM. Cell-free DNA in serum and plasma: comparison of ELISA and quantitative PCR. Clin Chem. 2005 Aug;51(8):1544-6. — View Citation

Naggara O, Raymond J, Domingo Ayllon M, Al-Shareef F, Touzé E, Chenoufi M, Gerber S, Mellerio C, Zuber M, Meder JF, Mas JL, Oppenheim C. T2* "susceptibility vessel sign" demonstrates clot location and length in acute ischemic stroke. PLoS One. 2013 Oct 11;8(10):e76727. doi: 10.1371/journal.pone.0076727. eCollection 2013. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of recanalisation	Correlation between NETs and stroke severity	24 hours
Secondary	Thrombus size on MRI	Correlation between NETs and stroke severity	24 hours
Secondary	Stroke volume on MRI	Correlation between NETs and stroke severity	24 hours