Ischemic Stroke, Inflammatory Response
Conditions
Brief summary
The goal of this (monocentric, randomised, placebo-controlled single-blinded; phase 2) clinical trial is to test the hypothesis that DNase 1 administration leads to a reduction in systemic immune response measured in patients after acute ischaemic stroke compared to control treatment. Participants will receive intravenous DNase 1 (500 µg/kg) or placebo (NaCl 0.9%) twice within 24±6 hours after symptom onset (last seen well). Blood samples will be taken at baseline, day 1 and 3. Personal visits will occur on baseline, day 1, 3 and discharge date. A telephone interview will be conducted on day 30±3.
Interventions
DRUGDornase Alfa
Patients will receive an intravenous dose of Dornase alfa twice within within 24±6 hours after symptom onset, administered as a bolus.
Patients will receive an intravenous dose of Isotonic saline solution twice within within 24±6 hours after symptom onset, administered as a bolus.
Sponsors
University Hospital Erlangen
University Hospital Regensburg
Ludwig-Maximilians - University of Munich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
Monocentric, randomised, placebo-controlled single-blinded, Phase 2 trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with suspected acute ischemic stroke with symptom onset (last-seen-well) until Investigational drug application of less than 12 hours. * Consent to participate in the study. * Age ≥ 18 years. * NIHSS ≥10 at admission.
Exclusion criteria
* Presence of any of the following conditions: Sinus or cerebral venous thrombosis, intracerebral haemorrhage, subarachnoid haemorrhage on qualified imaging (cCT with CT-A or MRI with MR-A). However, petechial haemorrhagic transformations of the index infarct and cerebral microhaemorrhages may be included. * Active malignant tumour disease in the last 6 months. * Current known immunosuppression due to immunomodulatory medication with immunosuppressive dose or underlying immunosuppressive disease (e.g. HIV). * Acute fulminant infectious disease in the last 7 days (fever \> 38.5°C or suspected by the Investigator). * Breastfeeding or pregnant woman, women of childbearing age without known use of contraceptives with positive urine or serum beta-human choriogonadotropin test. * Ischemic stroke or myocardial infarction in the previous 30 days. * Surgery in the previous 30 days, except minor dermatological or gynaecological surgery without anaesthesia and wound healing disorders and patients with thrombectomy. * Estimated or known weight \> 100 kg. * Known allergies or intolerance to dornase alfa (Pulmozyme) or recombinant protein products derived from Chinese hamster ovary cells. * Thrombocytopenia, leukocyte count \<1500/μl. * Known participation in another clinical trial investigating a drug and/or medical product in the last 7 days before study inclusion. * Severe renal insufficiency with GFR≤29 ml/min/ 1.73m³ and/or renal insufficiency requiring dialysis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of interleukin-1 beta in blood of patients with acute ischemic stroke receiving Dornase alfa compared to placebo treatment with Isotonic Saline Solution. | 24±6 hours after symptom onset | Outcome of reduced systemic immune response measured by interleukin-1 beta concentration \[pg/ml\] (at 24±6 hours after symptom onset) measured by Enzyme-linked Immunosorbent Assay (ELISA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DNase 1 activity in blood. | 24±6h after symptom onset | Comparison of DNase 1 activity \[µU/ml\] in blood of both treatment arms measured by Enzyme-linked Immunosorbent Assay (ELISA). |
| Concentration of DNase 1 in blood. | 24±6h after symptom onset | Analysis of the DNase 1 concentration \[ng/ml\] in patient blood treated with Dornase alfa compared to the placebo group by Enzyme-linked Immunosorbent Assay (ELISA). |
| Analysis of the composition of the leukocyte population in blood. | 24±6 hours after symptom onset | Analysing the leukocyte population \[%\] in blood using flow cytometry in both treatment arms. |
| Interleukin-6 concentration in blood after treatment. | 24±6 hours after symptom onset | Measurement of the interleukin-6 concentration \[pg/ml\] in blood samples (at 24±6 hours after symptom onset) measured by Enzyme-linked Immunosorbent Assay (ELISA). |
| cfDNA concentration in blood. | 24±6 hours after symptom onset | Measurement of cell-free DNA (cfDNA) concentration \[ng/ml\] in blood at day 1 (24±6 hours after symptom onset) compared to the placebo group with experimental analysis. |
| Assessment of patient safety after Dornase alfa treatment. | 30±3 days after symptom onset | Safety aspects of intravenous investigational drug administration in acute ischemic stroke patients will be assessed by monitoring all study patients for 30±3 days and analysis of their: * routine clinical diagnostics (worsening stroke is defined as a) progression, hemorrhagic transformation of the index stroke documented by radiological imaging; b) life-threatening need for intervention; c) death from the index stroke; and/or d) increasing disability (as measured by an increase of ≥ 4 points from the lowest NIHSS score measured during hospitalization, or a 1-point increase in mRS), * laboratory parameters (hemoglobin, platelets, neutrophil granulocytes, leukocytes, CRP, GFR, creatinine, IL-6) and * number of adverse events assessed by CTCAE current version. |
| Comparison of the incidence of infections and antibiotic treatment in both treatment arms. | 30±3 days after symptom onset | Comparing the incidence of infections and antibiotic treatment after Dornase alfa and Isotonic Saline Solution treatment over a period of 30±3 days after symptom onset. |
| Functional neurological outcome scores (National Institute of Health Stroke Scale [NIHSS, 0-42] and Modified Rankin Scale [mRS, 0-6]) at both treatment arms. | 30±3 days after symptom onset | Analysing changes of neurological scores (National Institute of Health Stroke Scale \[NIHSS, 0-42\] and Modified Rankin Scale \[mRS, 0-6\]) from baseline to last visit 30±3 days after symptom onset. |
| Caspase 1 concentration in blood after treatment. | 24±6 hours after symptom onset | Analysing the caspase 1 concentration \[pg/ml\] in blood (at 24±6 hours after symptom onset) measured by Enzyme-linked Immunosorbent Assay (ELISA). |
Countries
Germany
Contacts
Primary ContactArthur Liesz, Prof. Dr.
Backup ContactSaskia Wernsdorf
Outcome results
None listed