Clinical trial NCT05880524: Reduction of SystemiC Inflammation After Ischemic Stroke by Intravenous DNase Administration (ReSCInD)
Official title: Reduction of SystemiC Inflammation After Ischemic Stroke by Intravenous DNase Administration (ReSCInD)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Ischemic Stroke
Inflammatory Response
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
Collaborators: name: University Hospital Erlangen
name: University Hospital Regensburg
First posted: 2023-05-30
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Monocentric, randomised, placebo-controlled single-blinded, Phase 2 trial
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Concentration of interleukin-1 beta in blood of patients with acute ischemic stroke receiving Dornase alfa compared to placebo treatment with Isotonic Saline Solution.
timeFrame: 24±6 hours after symptom onset
Secondary outcomes:
measure: cfDNA concentration in blood.
timeFrame: 24±6 hours after symptom onset
measure: DNase 1 activity in blood.
timeFrame: 24±6h after symptom onset
measure: Concentration of DNase 1 in blood.
timeFrame: 24±6h after symptom onset
measure: Analysis of the composition of the leukocyte population in blood.
timeFrame: 24±6 hours after symptom onset
measure: Interleukin-6 concentration in blood after treatment.
timeFrame: 24±6 hours after symptom onset
measure: Caspase 1 concentration in blood after treatment.
timeFrame: 24±6 hours after symptom onset
measure: Assessment of patient safety after Dornase alfa treatment.
timeFrame: 30±3 days after symptom onset
measure: Comparison of the incidence of infections and antibiotic treatment in both treatment arms.
timeFrame: 30±3 days after symptom onset
measure: Functional neurological outcome scores (National Institute of Health Stroke Scale [NIHSS, 0-42] and Modified Rankin Scale [mRS, 0-6]) at both treatment arms.
timeFrame: 30±3 days after symptom onset
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Institute for Stroke and Dementia Research, Ludwig Maximilian University Munich, University Hospital
state: Bavaria
Study officials:
affiliation: Institute for Stroke and Dementia Research, LMU Hospital
name: Martin Dichgans, Prof. Dr.
role: STUDY_DIRECTOR
References: