CASTRO1 - Study on CRP Apheresis After Ischemic Stroke

Study Overview
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Brief Summary
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CASTRO1 is a study to investigate the reduction of C-reactive protein (CRP) by therapeutic apheresis (CRP-apheresis) in patients after primary treatment of ischemic stroke. The term therapeutic apheresis commonly refers to medical procedures, where pathogenic constituents are being removed from the circulating blood. Elimination is performed by adsorbers outside the body in an extracorporeal circulation. For removal of the pathogenic substances the plasma is separated from the blood (circulation) to pass the adsorber. The purified plasma is merged with the solid blood components thereafter and returned to the patient. The adsorber PentraSorb® CRP used for CRP apheresis is CE-certified. It is designated to the selective depletion of C-reactive protein from human blood.

Detailed Description
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The purpose of the study is to evaluate the safety and efficacy of CRP apheresis in patients following ischemic stroke. CRP apheresis is to be conducted with the aim of reducing cerebral damage following the guideline-appropriate primary therapy of ischemic stroke. A possible protective effect of CRP apheresis will be assessed by clinical scores, laboratory determination of immunologic parameters and determination of the size of the infarct area by magnetic resonance imaging (MRI). The study will be randomized, controlled and monocentric.

Official Title
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Selective Depletion of C-reactive Protein by Therapeutic Apheresis (CRP-apheresis) in Ischemic Stroke

Conditions
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Stroke, Ischemic

Intervention / Treatment
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* Device: CRP apheresis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ischaemic stroke with determination of infarct size by imaging (MRI) NIHSS 1-24 CRP increase ≥ 5 mg/l within presumed 72 hours after stroke and/or CRP value > 10 mg/l written informed consent of the patient or his legal representative Exclusion Criteria: age < 18 years Severe dysphagia (danger of aspiration pneumonia) Clinical or laboratory evidence of a severe systemic infection Participation in other interventional studies Contraindications against apheresis therapy Modified Rankin Scale (mRS) before index event ≥ 3 Intracranial hemorrhage Epileptic seizure in the context of the acute event Pregnancy, lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apheresis group<br>10 patients receive a maximum of 3 apheresis treatments at intervals of 24 ± 12 hours each (from the beginning of the preceding treatment). The first treatment starts within 72 hours after infarction or, in case of an unclear time window, within presumed 72 hours after the patient was last seen free of symptoms. No further treatments are carried out if the CRP concentration before the start of a treatment is <10 mg/l or if the patient has been discharged from hospital. For each treatment, 1.5 - 2.5 times the plasma volume is processed. The duration of each treatment is approximately 4-6 hours. | Device: CRP apheresis<br>* Selective CRP apheresis by use of the PentraSorb-CRP<br>|
| No Intervention: Control group<br>10 patients of the control group receive the same examinations as arm 1 (verum group) but no apheresis treatments after ischemic stroke. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of CRP apheresis | Incidence of expected and unexpected adverse effects | 24 hours after each apheresis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stroke Severity | National Institute of Health Stroke Scale (NIHSS) score - ranging from 0-42 - higher values represent a worse outcome | before first apheresis and 6 ± 3 days after infarction and 12 ± 2 weeks after infarction | 
| Functional Outcome | Modified ranking scale (mRS) score - ranging from 0-6 with higher scores signifying worse outcome | before first apheresis and 6 ± 3 days after infarction and 12 ± 2 weeks after infarction | 
| Dependency | Barthel Index (BI) - ranging from 0-100 with higher scores signifying better outcome | 6 ± 3 days after infarction and 12 ± 2 weeks after infarction | 
| Infarct size | Infarct growth measured via diffusion-weighted imaging (DWI)-FLAIR volume change | 6 ± 3 days after infarction and 12 ± 2 weeks after infarction | 
| Concentration of inflammatory biomarkers (CRP, IL-6, SAA) | CRP, Interleukin-6, and serum amyloid A are determined twice daily until discharge of the patient (for a maximum of 7 days). | 0-7 days after infarction |