Dengzhanxixin Injection for Acute Ischemic Stroke Receiving Reperfusion Therapy

A Phase II, Randomized, Double-blind, Placebo-controlled, Dose-Finding, Multi-center Study to Assess the Efficacy and Safety of Dengzhanxixin Injection in Patients With Acute Ischemic Stroke Receiving Reperfusion Therapy

To assess the Efficacy and Safety of Dengzhanxixin Injection in Patients With Acute Ischemic Stroke Receiving Reperfusion Therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Dengzhanxixin Injection; Drug: Placebo injection

Detailed Description

To evaluate the safety and efficacy of Dengzhanxixin at different doses of 80ml/day, 40 ml/day, or placebo within 24 hours after the onset of ischemic stroke. The primary objective of this study is the proportion of subjects with excellent outcomes defined as mRS (0-1) among the three treatment groups at 90 days.

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100070
      • Beijing Tiantan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• More than or equal to 18 years old and less than 80 years old;
• Acute ischemic stroke confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) of the head;
• Stroke onset within 24 hours and can be treated with study drug within 24 hours of symptoms onset；
• The patient has received or is planning to receive vascular reperfusion therapy after onset；
• Baseline NIHSS score is ≥4 and ≤26.
• mRS ≤1 prior onset.
• Informed consent signed.

Exclusion Criteria:

• Intracranial hemorrhage: cerebral hemorrhage, subarachnoid hemorrhage, etc.;
• The acute infarcts lesion Involvement of more than one-third of middle cerebral artery (MCA) territory on initial brain imaging;
• Rapidly improving symptoms at the discretion of the investigator;
• Patients who have taken Dengzhanxixin Injection，edaravone or other brain protective drugs after onset ;
• History of intracranial hemorrhage；
• History of severe head trauma, stroke or myocardial infarction in past 3 months;
• Diagnosised intracranial tumor and giant intracranial aneurysm；
• Diagnosised aortic arch dissection；
• Undergoing major surgery within 2 weeks prior to screening; or intracranial or intraspinal surgery within 3 months prior to screening;
• Currently accompanied by active visceral bleeding; or arterial puncture at a site that is not easy to compress hemostasis within 1 week before screening; or gastrointestinal or urinary system bleeding occurred within 3 weeks before screening;
• Those with acute bleeding tendency, including: platelet count <100×109/L, combined with hemophilia, etc.; or those with partially activated thrombin time greater than 3 times the upper limit of normal;
• Oral anticoagulants, and international normalized ratio>1.7 or prothrombin time>15s;
• Diagnosed primary liver and kidney disease, AST or ALT (>2 times the ULN), serum creatinine >2.0mg/dL or >176.8µmol/L;
• Persistent blood pressure elevation ( systolic ≥180 mmHg or diastolic ≥100 mmHg ), despite blood pressure lowering treatment;
• Those with a history of epilepsy or epilepsy-like symptoms at the onset of stroke;
• Complete atrioventricular block; or according to the New York Heart Association (NYHA) cardiac function class II or above; or have been hospitalized due to congestive heart failure within 6 months before screening;
• Pregnant women, nursing mothers, or reluctant to agree taking effective contraceptive measures during the period of trial subjects;
• Those who have other neurological diseases or disabilities or mental diseases, which may affect the efficacy evaluation of this study as judged by the investigator;
• Those with a history of malignant tumor within 5 years before screening (if the patient has basal cell carcinoma of the skin or carcinoma in situ of the cervix and has been cured, he/she can participate in this study);
• Those who participated in other drug/device clinical studies and used the experimental drug/device within 3 months before screening;
• Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study。

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose Arm; Dengzhanxixin injection 40ml/day, placebo 40ml/day. Dengzhanxixin injection 40ml, diluted with 250ml of 0.9% sodium chloride injection and then slowly intravenously infused once a day; placebo injection 40ml, diluted with 250ml of 0.9% sodium chloride injection and then slowly intravenously infused once a day.	Drug: Dengzhanxixin Injection; Experimental arms for low, and high dose for the standard protocol; Other Names: Dengzhanxixin Zhusheye
Experimental: High Dose Arm; Dengzhanxixin injection 80ml/day. Dengzhanxixin injection 40ml, diluted with 250ml of 0.9% sodium chloride injection, and then slowly intravenously infused twice a day.	Drug: Dengzhanxixin Injection; Experimental arms for low, and high dose for the standard protocol; Other Names: Dengzhanxixin Zhusheye
Placebo Comparator: Placebo Arm; Placebo injection 80ml/day. Placebo injection 40ml, diluted with 250ml of 0.9% sodium chloride injection, and then slowly intravenously infused twice a day.	Drug: Placebo injection; placebo control arm for the standard protocol; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Efficacy Outcome	Proportion of subjects of excellent outcome defined as modified Rankin Scale (mRS) (0-1) at 90 days. mRS is a 7 grade scale from 0 to 6, where 0 is the best and 6 is the worst outcome.	90 days
Primary Safety Outcome	Proportion of patients with adverse events at 90 days.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infarction Volume	Infarction volume at 14 days compared to baseline	14 days
National Institutes of Health Stroke Scale (NIHSS)	National Institutes of Health Stroke Scale (NIHSS) score changes from baseline. NIHSS is 42 point scale where 0 is the best o and 42 is the worst outcome.	72 hours， 7 days， 14 days， 90days
Excellent functional outcome	Favourable outcome rate is defined as the proportion of subjects with modified Rankin Scale (mRS) (0-1). mRS is a 7 grade scale from 0 to 6, where 0 is the best and 6 is the worst outcome.	14 days
Modified Rankin Scale (mRS) distribution	Ordinal distribution of Modified Rankin Scale (mRS). mRS is a 7 grade scale from 0 to 6, where 0 is the best and 6 is the worst outcome.	14 days， 90 days
Barthel index (BI)	Proportion of subjects with Global function of daily living defined as Change in Barthel index (BI) ≥ 95. BI is a 10 item scale with scores ranging from 0 to 100, where a score of 100 is the best and 0 is the worst outcome.	90 days
Symptomatic intracranial hemorrhage(sICH)	Proportion of subjects with symptomatic intracranial hemorrhage (sICH)	14 days
AEs	Proportion of subjects with AEs	72 hours，7 days， 14 days
SAEs	Proportion of subjects with SAEs	72 hours，7 days， 14 days，90days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkes	The changes of serum high sensitivity C-reactive protein test (hs-CRP) level from baseline to 14 days	14 days

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Yongjun Wang, M.D., Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2022
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: November 16, 2022
• First Submitted That Met QC Criteria: January 16, 2023
• First Posted (Estimate): January 26, 2023

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 16, 2023
• Last Verified: January 1, 2023

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; Cerebral Infarction
• Other Study ID Numbers: NCRC-2022-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No