Reduction of SystemiC Inflammation After Ischemic Stroke by Intravenous DNase Administration (ReSCInD) (ReSCInD)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Ischemic Stroke; Inflammatory Response
• Intervention / Treatment: Drug: Dornase Alfa; Drug: Isotonic Saline Solution

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Arthur Liesz, Prof. Dr.; Phone Number: +49 89 4400 46242; Email: arthur.liesz@med.uni-muenchen.de
• Study Contact Backup: Name: Saskia Wernsdorf; Phone Number: +49 89 4400 46119; Email: saskia.wernsdorf@med.uni-muenchen.de

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 81377
      • Institute for Stroke and Dementia Research, Ludwig Maximilian University Munich, University Hospital
      • Contact: Arthur Liesz, Prof. Dr.; Phone Number: +49 89 4400 46242; Email: arthur.liesz@med.uni-muenchen.de
      • Contact: Saskia Wernsdorf; Phone Number: +49 89 4400 46119; Email: saskia.wernsdorf@med.uni-muenchen.de
      • Principal Investigator: Martin Dichgans, Prof. Dr.
      • Sub-Investigator: Arthur Liesz, Prof. Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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: Pulmozyme
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: NaCl 0,9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of interleukin-1 beta in blood of patients with acute ischemic stroke receiving Dornase alfa compared to placebo treatment with Isotonic Saline Solution.	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).	24±6 hours after symptom onset

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cfDNA concentration in blood.	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.	24±6 hours after symptom onset
DNase 1 activity in blood.	Comparison of DNase 1 activity [µU/ml] in blood of both treatment arms measured by Enzyme-linked Immunosorbent Assay (ELISA).	24±6h after symptom onset
Concentration of DNase 1 in blood.	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).	24±6h after symptom onset
Analysis of the composition of the leukocyte population in blood.	Analysing the leukocyte population [%] in blood using flow cytometry in both treatment arms.	24±6 hours after symptom onset
Interleukin-6 concentration in blood after treatment.	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).	24±6 hours after symptom onset
Caspase 1 concentration in blood after treatment.	Analysing the caspase 1 concentration [pg/ml] in blood (at 24±6 hours after symptom onset) measured by Enzyme-linked Immunosorbent Assay (ELISA).	24±6 hours after symptom onset
Assessment of patient safety after Dornase alfa treatment.	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.	30±3 days after symptom onset
Comparison of the incidence of infections and antibiotic treatment in both treatment arms.	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.	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.	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.	30±3 days after symptom onset

Collaborators and Investigators

• Sponsor: Ludwig-Maximilians - University of Munich
• Collaborators: University Hospital Erlangen; University Hospital Regensburg
• Investigators: Study Director: Martin Dichgans, Prof. Dr., Institute for Stroke and Dementia Research, LMU Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: April 30, 2023
• First Submitted That Met QC Criteria: May 19, 2023
• First Posted (Actual): May 30, 2023

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Inflammation; Cerebral Infarction
• Other Study ID Numbers: RESCIND-1-2023; 2022-003410-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No