NCT07364344

Safety and Preliminary Efficacy of Hibernation-Like Therapy (Chlorpromazine and Promethazine) in Patients With Acute Ischemic Stroke (AIS) Eligible for Reperfusion Therapy.

A Single-Center,Open-Label Clinical Study on the Safety and Preliminary Efficacy of Hibernation-Like Therapy (Chlorpromazine and Promethazine) in Patients With Acute Ischemic Stroke (AIS) Eligible for Reperfusion Therapy.

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 57 (estimated)
• Sponsor: Ji Xunming,MD,PhD · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

This is a single-center, dose-escalation and dose-expansion Phase I study designed to evaluate the safety of hibernation-like therapy (Chlorpromazine and Promethazine, C+P) and observe improvements in infarct volume in patients with AIS eligible for reperfusion therapy.

Detailed description

Part A is the dose-escalation phase, and Part B is the dose-expansion phase. Both Part A and Part B will enroll subjects with AIS who are eligible for endovascular treatment based on multimodality imaging assessment and who meet all inclusion criteria and none of the exclusion criteria as evaluated by the investigator. Successfully screened patients will first enter the dose-escalation study. The escalating doses are Chlorpromazine and Promethazine (C+P) at the following combinations: 50mg+50mg, 62.5mg+62.5mg, 75mg+75mg, and 100mg+100mg. Dose escalation will follow the "3+3" rule, with a planned enrollment of 12-24 subjects. Based on the dose-escalation results, dose expansion will be initiated at an appropriate time. The dose-expansion phase will consist of three cohorts: two cohorts receiving C+P and one cohort receiving an intravenous infusion of 50ml normal saline at room temperature (infusion rate also 50ml/h) prior to endovascular treatment. The two C+P dose groups for expansion will be selected based on the dose-escalation results. Patients will receive the study drug followed by reperfusion therapy. The administration method is the same as in the dose-escalation phase. The dose-expansion phase plans to enroll 33 subjects (10 subjects each in the two C+P cohorts and 13 subjects in the normal saline cohort). See the figure below for details. C+P is administered intravenously. The administration regimen involves dissolving C+P in 50ml of normal saline at room temperature and infusing it intravenously at a rate of 50ml/h (complete infusion over 1 hour). Subsequently, the patient will undergo endovascular thrombectomy for recanalization. The DLT observation period in the dose-escalation phase is 3 days after administration. Escalation to the next dose cohort may proceed only after the DLT observation period for the current cohort is completed and safety is confirmed. Patients will receive only a single administration during both the dose-escalation and dose-expansion phases. Within 24 hours after completing endovascular thrombectomy, patients will undergo ECG monitoring with close observation of vital signs and changes in consciousness level. Vital signs will continue to be monitored for up to 72 hours post-thrombectomy, and imaging follow-up will be performed at 48 ±12 hours. Study Objectives: * Primary Objective: To evaluate the safety of hibernation-like therapy (Chlorpromazine + Promethazine, C+P) in patients with acute ischemic stroke (AIS) eligible for reperfusion therapy, to observe the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) across different C+P dose cohorts, and to determine the recommended phase 2 dose (RP2D). * Secondary Objective: To evaluate the efficacy of hibernation-like therapy (C+P) in patients with AIS eligible for reperfusion therapy. * Exploratory Objective: To observe changes in metabolomics at 3 hours post-administration compared to baseline. Endpoints: * Primary Endpoint: Observation of DLT and MTD across different C+P dose cohorts to determine the RP2D. * Secondary Endpoints: * Improvement in cerebral infarct volume (mL) at 48 ±12 hours post-treatment compared to pre-treatment. * Improvement in the National Institutes of Health Stroke Scale (NIHSS) score at 24 hours post-treatment compared to baseline. * Assessment of other safety parameters. * Exploratory Endpoint: Changes in metabolomics at 3 hours post-administration compared to pre-administration.

Conditions

• Acute Ischemic Stroke

Interventions

Type	Name	Description
DRUG	Hibernation-like Therapy (Chlorpromazine and Promethazine, C+P)	The escalating doses are Chlorpromazine and Promethazine (C+P) at the following combinations: 50mg+50mg, 62.5mg+62.5mg, 75mg+75mg, and 100mg+100mg.Dose escalation will follow the "3+3" rule. Based on the dose-escalation results, dose expansion will be initiated at an appropriate time. The dose-expansion phase will consist of three cohorts: two cohorts receiving C+P and one cohort receiving an intravenous infusion of 50ml normal saline at room temperature (infusion rate also 50ml/h) prior to endovascular treatment. The two C+P dose groups for expansion will be selected based on the dose-escalation results. Patients will receive the study drug followed by reperfusion therapy. The administration method is the same as in the dose-escalation phase.

Timeline

• Start date: 2026-01-01
• Primary completion: 2026-07-01
• Completion: 2026-07-01
• First posted: 2026-01-23
• Last updated: 2026-01-23