Reduction of SystemiC Inflammation After Ischemic Stroke by Intravenous DNase Administration (ReSCInD)
- Conditions
- Inflammatory ResponseIschemic Stroke
- Interventions
- Drug: Isotonic Saline Solution
- Registration Number
- NCT05880524
- Lead Sponsor
- Ludwig-Maximilians - University of Munich
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 36
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Isotonic Saline Solution Isotonic Saline Solution NaCl 0,9 %; intravenous administration; 0,5 ml/kg Pulmozyme Dornase Alfa Dornase alfa; intravenous administration; 500 µg/kg
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.
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).
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).
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.
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.
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).
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).
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.
Trial Locations
- Locations (1)
Institute for Stroke and Dementia Research, Ludwig Maximilian University Munich, University Hospital
🇩🇪Munich, Bavaria, Germany