Acute Ischemic Stroke
Conditions
Keywords
Hibernation-like status, Reperfusion, Neuroprotection, phenothiazine, dose-escalation
Brief summary
The goal of this clinical trial is to learn whether chlorpromazine and promethazine（C+P）is safe in Acute Ischemic Stroke（AIS) patients and determine the maximum dosage. It will also evaluate the preliminary efficacy of C+P in AIS. The main questions it aims to answer are: What is the optimal dosage of C+P that is safe without causing adverse effects in AIS patients? What is the optimal dosage of C+P that potentially works to treat AIS? Researchers will compare C+P with placebo (saline solution without C+P) to see if C+P is safe and effective in treating Acute Ischemic Stroke. Participants will: Receive C+P or placebo at the same time as endovascular thrombectomy begins. Patients will be observed for 72 hours to see if there were any adverse effects related to C+P. Infarct volumes will be evaluated using Computed Tomography. Functional outcomes will be assessed at 90 days.
Detailed description
Chlorpromazine and promethazine (C+P), due to their effort to induce a hibernation-like status, has been proved to be neuroprotective for ischemic stroke in pre-clinical experiments. However, whether it is safe and potentially effective in acute ischemic stroke (AIS) patients is currently unknown. The reason might be that the optimal dosage is not defined in AIS treatment. High dosage of C+P might result in hypotension and extrapyramidal symptoms that diminishes its neuroprotective effect. So it is essential to determine a safe and potentially dosage. Another reason might be that patients from previous clinical trials assessing the effectiveness of C+P did not receive reperfusion therapy. In this study，we plan to conduct a 6+2 dose-escalation clinical trial to determine the safety of C+P in AIS patients receiving endovascular thrombectomy. Four dosage groups of C+P will be set(10mg/20mg/50mg/100mg).A minimum of 32 patients will be involved if no drug related severe adverse event(SAE) was observed. A maximum of 64 patients will be required if one SAE is observed in each group. The current study aim to provide a basis for phase Ⅱ clinical trial to further explore the efficacy of C+P in AIS treatmment.
Interventions
DRUGchlorpromazine and promethazine
C+P were diluted to 50 ml saline solution and delivered intravenously at the beginning of endovascular thrombectomyat a velocity of 4ml/h. The whole period of drug delivery lasts for approximately 12h.
DRUGPlacebo group
50 ml saline solution was set as placebo and delivered intravenously at the beginning of endovascular thrombectomyat a velocity of 4ml/h. The whole period of drug delivery lasts for approximately 12h.
PROCEDUREendovascular thrombectomy
All patients that are eligible for endovascular thrombectomy will receive this surgery in aim to remove thrombus and restore reperfusion.
DRUGrt-PA
All patients that are eligible for Intravenous thrombolysis will receive 0.9mg/kg rt-PA in aim to remove thrombus and restore reperfusion
Sponsors
Linyi People's Hospital
Capital Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Clinical Inclusion Criteria: 1. Age between 18-80 years(including the critical value) 2. Ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score ranging from 6-20 3. Time from last known to be well to randomization within 24h 4. Pre-stroke Modified Rankin Scale scoring 0-1. 5. With indications of reperfusion therapy (including intravenous thrombolysis and endovascular thrombectomy). 6. Informed consent signed by patients or their legal relatives. 7. CT angiography (CTA) confirmed large vessel occlusion of anterior circulation 8. Alberta Stroke Program Early Computed Tomography Score (ASPECT) score of 6-10. 9. initial infarct volume on CT perfusion (CTP) lesser than 70ml; a ratio of hypoperfused volume to infarcted volume greater than 1.8; absolute mismatch volume greater than 15 ml according to DEFUSE-3 trial.
Exclusion criteria
* Clinical
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The incidence and severity of all adverse events (AEs) and severe adverse events (SAEs) | 72 hours after randomization | AEs including: 1. Severe hypothermia with body temperature\<32 degree centigrade 2. Severe hypotension with systolic blood pressure\<90mmHg that needs additional support 3. Any forms of intracranial hemorrhage 4. Coma 5. Death within 72h 6. Respiratory depression defined as respiration rate\<8 bpm/min 7. Extrapyramidal symptoms including Parkinsonism, dystonia, dyskinesia. AEs are defined as severe adverse events(SAEs) if severity reaches grade 3-5 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) ver. 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Scores of National institutes of health stroke scale (NIHSS) | 24 hours after randomization | Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 to 42, with higher scores indicating worse neurologic deficit. |
| Infarct volume | 72 hours after randomization | Infarct volume is assessed by Computed Tomography and automatically calculated by software. |
| Plasma proteomics and metabolomics | 24 hours±6 hours | Proteomics and metabolomics will be performed using patients' plasma. The purpose is to determine what proteins or metabolites are mediated by C+P and correlated with favorable outcome. |
Countries
China
Contacts
Primary ContactXunming Ji, Doctor
Backup ContactHao Wang, Doctor
Outcome results
None listed