Neutrophil Extracellular Traps and Thrombolysis in the Acute Stroke

NCT ID: NCT02476188

Last Updated: 2017-10-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2016-11-30

Brief 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.

Detailed 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.

Conditions

Acute Stroke

Keywords

Neutrophil extracellular traps, stroke

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Patients

Samples of blood at H0, H+6, H+24 and H+72

Group Type: EXPERIMENTAL

Sample of Blood

Intervention Type: PROCEDURE

Patients control

Samples of blood at H0

Group Type: EXPERIMENTAL

Sample of Blood

Intervention Type: PROCEDURE

Control (healthy person)

Samples of blood at H0

Group Type: ACTIVE_COMPARATOR

Sample of Blood

Intervention Type: PROCEDURE

Interventions

Sample of Blood

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

University of Paris 5 - Rene Descartes

OTHER

Sponsor Role: collaborator

Centre Hospitalier St Anne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michel PLOTKINE, PhD

Role: STUDY_DIRECTOR

University of Paris 5 - Rene Descartes

Locations

Centre Hospitalier Sainte-Anne

Paris, , France

Countries

France

References

Holdenrieder S, Stieber P, Bodenmuller H, Fertig G, Furst 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. doi: 10.1515/CCLM.2001.095.

Reference Type: BACKGROUND

PMID: 11522104 (View on PubMed)

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. doi: 10.1373/clinchem.2005.049320. No abstract available.

Reference Type: BACKGROUND

PMID: 16040855 (View on PubMed)

Naggara O, Raymond J, Domingo Ayllon M, Al-Shareef F, Touze 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.

Reference Type: BACKGROUND

PMID: 24146915 (View on PubMed)

Other Identifiers

D15-P007

Identifier Type: -

Identifier Source: org_study_id