Reduction of SystemiC Inflammation After Ischemic Stroke by Intravenous DNase Administration (ReSCInD)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 10
- 主要终点
- Concentration of interleukin-1 beta in blood of patients with acute ischemic stroke receiving Dornase alfa compared to placebo treatment with Isotonic Saline Solution.
研究概览
简要总结
The goal of this (multicentric, 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Isotonic Saline Solution
NaCl 0,9 %; intravenous administration; 0,5 ml/kg
干预措施: Isotonic Saline Solution (Drug)
Pulmozyme
Dornase alfa; intravenous administration; 500 µg/kg
干预措施: Dornase Alfa (Drug)
结局指标
主要结局
Concentration of interleukin-1 beta in blood of patients with acute ischemic stroke receiving Dornase alfa compared to placebo treatment with Isotonic Saline Solution.
时间窗: 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).
The primary endpoint, IL-1 β concentration in the blood within 24±6 hrs after symptom onset, will be analyzed in the full analysis set, which comes as close as possible to the IIT principle. A mixed linear regression model is calculated with the IL-1 β value (at 24±6hrs & 3 d) as the dependent variable, the randomized group, the IL-1 β value at baseline & the time point, the interaction of time + group, as independent variables and the patient as a random effect.
The primary endpoint, IL-1 β concentration in the blood within 24±6 hrs after symptom onset, will be analyzed in the full analysis set, which comes as close as possible to the IIT principle. A mixed linear regression model is calculated with the IL-1 β value (at 24±6hrs & 3 d) as the dependent variable, the randomized group, the IL-1 β value at baseline & the time point, the interaction of time + group, as independent variables and the patient as a random effect.
次要结局
- cfDNA concentration in blood.(24±6 hours after symptom onset)
- DNase 1 activity in blood.(24±6h after symptom onset)
- Concentration of DNase 1 in blood.(24±6h after symptom onset)
- Analysis of the composition of the leukocyte population in blood.(24±6 hours after symptom onset)
- Interleukin-6 concentration in blood after treatment.(24±6 hours after symptom onset)
- Caspase 1 concentration in blood after treatment.(24±6 hours after symptom onset)
- Assessment of patient safety after Dornase alfa treatment.(30±3 days after symptom onset)
- Comparison of the incidence of infections and antibiotic treatment in both treatment arms.(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)
- All secondary endpoints are analyzed descriptively, and differences between the two study arms are explored according to their level of measurement.
研究者
Martin Dichgans
Sponsor-Delegated Person and Principal Investigator
Ludwig-Maximilians - University of Munich