Hibernation-like therapy for treating acute ischemic stroke
The Safety and effiCacy of HIbernation-Like Therapy Combining recanaLization in Ischemic Stroke: a Phase 1, Dose-escalation Study
This study is testing if a combination of two medications can safely help people who have had a stroke during a specific treatment procedure.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 32 (estimated) |
| Ages | 18 Years to 80 Years |
| Sex | All |
| Sponsor | Capital Medical University Academic / other |
| Locations | 1 site (Linyi, Shandong) |
| Trial ID | NCT06663631 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to evaluate the safety and preliminary efficacy of chlorpromazine and promethazine (C+P) in patients with acute ischemic stroke (AIS) undergoing endovascular thrombectomy. Participants will receive either C+P or a placebo at the start of the procedure, and their health will be monitored for 72 hours to assess any adverse effects. The study will also determine the optimal dosage of C+P that is safe and potentially effective for treating AIS, comparing outcomes using imaging and functional assessments at 90 days. The trial employs a dose-escalation approach to identify the maximum tolerated dose without significant side effects.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18-80 with a confirmed diagnosis of acute ischemic stroke and specific eligibility criteria related to stroke severity and timing.
Not a fit: Patients with contraindications for reperfusion therapy or those with severe intracranial hemorrhage will not benefit from this study.
Why it matters
Potential benefit: If successful, this therapy could provide a new neuroprotective treatment option for patients suffering from acute ischemic stroke.
How similar studies have performed: While pre-clinical studies have shown promise for C+P in neuroprotection, this specific approach in AIS patients is novel and has not been extensively tested in prior clinical trials.
Eligibility criteria
Show full inclusion / exclusion criteria
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 Exclusion Criteria:
1. Clinical findings suggest intracranial parenchymal hemorrhage or subarachnoid hemorrhage.
2. Accompanied by epilepsy.
3. Accompanied by coma or mental disorders, may interfere with neurological function assessment.
4. History of premorbid phenothiazine allergy or contraindication.
5. History of allergy to iodine contrast medium or anaphylactic shock
6. Baseline blood glucose \<50mg/dL (2.78mmol) or \>400mg/dL (22.20mmol)
\* Acceptable fingertip blood glucose results
7. Baseline platelet \<50×109 /L
8. Recent (i.e. within 30 days prior to randomization) history of gastrointestinal or other clinically significant bleeding; Active bleeding, abnormal clotting factors, or bleeding tendency (INR≥3 or PT≥3×ULN on anticoagulants; If the investigator believes that the subject does not have coagulation dysfunction, it is not necessary to wait for the results of the coagulation test before deciding whether to enroll.)
9. The stroke is accompanied by fever, or there is an active infection requiring systemic treatment (such as active tuberculosis, etc.)
10. Expected survival less than 90 days (According to the Chinese Guidelines for Early Endovascular Interventional Diagnosis and Treatment of Acute Ischemic Stroke 2022, expected survival less than 90 days is a contraindication for endovascular therapy)
11. A history of severe cardiovascular disease, including but not limited to: uncontrolled hypertension (systolic blood pressure \>180 mmHg or diastolic blood pressure \>105 mmHg after standard treatment), hypotension (systolic blood pressure ≤100 mmHg after standard treatment), or pulmonary hypertension; Had unstable angina pectoris, myocardial infarction, or bypass or stent surgery within 6 months before randomization; New York Heart Association (NYHA) grade 3-4 history of chronic heart failure; Clinically significant valvular disease; Severe arrhythmias requiring treatment (except atrial fibrillation and paroxysmal supraventricular tachycardia), including QT interval ≥450ms for men and ≥470ms for women
12. accompanied by chronic obstructive pulmonary disease（COPD）, tuberculosis, pneumonia, pneumothorax, atelectasis, pulmonary fibrosis, bronchopulmonary dysplasia, pleural effusion, acute respiratory distress syndrome, respiratory irregularity and other lung diseases
13. Severe hepatic and renal insufficiency, including but not limited to: cirrhosis, hepatic encephalopathy, ascites, renal failure or uremia (Ccr\<25ml/min), hepatorenal syndrome, etc
14. Pregnancy or lactating women
15. Participation in other clinical trials and have used an investigational drug or medical device
16. Patients that may not be able to complete the study for other reasons or who the investigator believes should not be included
* Image exclusion criteria:
1. computed tomographic angiography（CTA）/magnetic resonance angiography（MRA）/digital substraction angiography（DSA） shows excessive vascular curvature, which may hinder delivery of interventional devices
2. Cerebrovascular inflammation is suspected based on medical history and CTA/MRA/DSA
3. Aortic dissection is suspected based on medical history and CTA/MRA/DSA
4. CTA/MRA/DSA confirmed multi-vascular regional occlusion (such as bilateral anterior circulation or anterior/posterior circulation, extracranial carotid artery with intracranial tandem lesions), or clinical evidence of bilateral or multi-regional infarction
5. CTA/MRA/DSA confirms moyamoya disease or moyamoya syndrome
6. CT/MRI confirmed a significant midline shift effect
7. CT/MRI confirms the presence of intracranial tumors (except cerebellar meningioma) CT/MRI confirmed intracranial hemorrhage
Where this trial is running
Linyi, Shandong
- Linyi People's Hospital — Linyi, Shandong, China (Recruiting)
Study contacts
- Study coordinator: Xunming Ji, Doctor
- Email: Jixm@ccmu.edu.cn
- Phone: +86 13911077166
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.