Reduction of SystemiC Inflammation After Ischemic Stroke by Intravenous DNase Administration (ReSCInD)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Pulmozyme Dornase alfa; intravenous administration; 500 µg/kg |
Drug: Dornase Alfa
Patients will receive an intravenous dose of Dornase alfa twice within within 24±6 hours after symptom onset, administered as a bolus.
Other Names:
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| Placebo Comparator: Isotonic Saline Solution NaCl 0,9 %; intravenous administration; 0,5 ml/kg |
Drug: Isotonic Saline Solution
Patients will receive an intravenous dose of Isotonic saline solution twice within within 24±6 hours after symptom onset, administered as a bolus.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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).
- 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).
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients with suspected acute ischemic stroke with symptom onset (last-seen-well) until Investigational drug application of less than 12 hours.
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Consent to participate in the study.
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Age ≥ 18 years.
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NIHSS ≥10 at admission.
Exclusion Criteria:
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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.
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Active malignant tumour disease in the last 6 months.
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Current known immunosuppression due to immunomodulatory medication with immunosuppressive dose or underlying immunosuppressive disease (e.g. HIV).
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Acute fulminant infectious disease in the last 7 days (fever > 38.5°C or suspected by the Investigator).
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Breastfeeding or pregnant woman, women of childbearing age without known use of contraceptives with positive urine or serum beta-human choriogonadotropin test.
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Ischemic stroke or myocardial infarction in the previous 30 days.
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Surgery in the previous 30 days, except minor dermatological or gynaecological surgery without anaesthesia and wound healing disorders and patients with thrombectomy.
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Estimated or known weight > 100 kg.
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Known allergies or intolerance to dornase alfa (Pulmozyme) or recombinant protein products derived from Chinese hamster ovary cells.
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Thrombocytopenia, leukocyte count <1500/μl.
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Known participation in another clinical trial investigating a drug and/or medical product in the last 7 days before study inclusion.
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Severe renal insufficiency with GFR≤29 ml/min/ 1.73m³ and/or renal insufficiency requiring dialysis.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institute for Stroke and Dementia Research, Ludwig Maximilian University Munich, University Hospital | Munich | Bavaria | Germany | 81377 |
Sponsors and Collaborators
- Ludwig-Maximilians - University of Munich
- University Hospital Erlangen
- University Hospital Regensburg
Investigators
- Study Director: Martin Dichgans, Prof. Dr., Institute for Stroke and Dementia Research, LMU Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RESCIND-1-2023
- 2022-003410-37