Danhong Injection in the Treatment of Acute Ischemic Stroke

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Danhong injection is effective in the treatment of acute ischemic stroke.

Official Title
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A Randomized, Multi-center, Double-blind, Placebo-controlled Trial of Danhong Injection in the Treatment of Acute Ischemic Stroke

Conditions
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Acute Stroke

Intervention / Treatment
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* Drug: Danhong injection
* Procedure: Standard medical care
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male inpatients Age: 18 - 70 years. Clinical diagnosis of ischemic stroke causing a measurable neurological deficit defined as impairment of language, motor function, cognition and/or gaze, vision or neglect. Ischemic stroke is defined as an event characterized by the sudden onset of an acute focal neurologic deficit presumed to be due to cerebral ischemia after CT scan excludes hemorrhage. Clinical diagnosis of Xueyu Zheng (Blood Stasis Syndrome) as the scores of Chinese medicine symptoms scales of Xueyu Zheng in ischemic stroke ≥ 20. The Chinese medicine symptoms scales of Xueyu Zheng is defined as following (1)hemiplegia-10,(2)numbness of limbs-10，(3) dark face-9,(4)purple or dark lip-8,(5)Roughness of skin-4, (6) pain with fixed point-5, (7) purple or dark tongue-10,(8)ecchymosis on tongue-10,(9)purple sublingual vessel-10,(10)varicose sublingual vessel-8,(11)unsmooth pulse-8,(12)intermittent pulse-1. Onset of symptoms in 1 week prior to initiation of administration of study drug. Clinical diagnosis of cerebral anterior circulation obstruction. 4≤NIHSS<20. Patient is willing to participate voluntarily and to sign a written patient informed consent. Informed consent will be obtained from each patient or the subject's legally authorized representative or relatives, or deferred where applicable, according to the regulatory and legal requirements of the participating centers. Exclusion Criteria: Evidence of intracranial hemorrhage (ICH) or other cerebral diseases (eg.vascular malformation, tumor, abscess or multiple sclerosis etc.)on the CT-or MRI-scan. Patients with thrombolysis or endovascular treatment. Known history of allergy or suspected allergic to the drug. Blood glucose 2.8 or > 16.8 mmol / l under the treatment of diabetes or with severe complications due to diabetes (eg. peripheral neuropathy, diabetic gangrene). Liver function impairment with the value of ALT or AST over 1.5-fold of normal value. Renal dysfunction with the value of serum creatinine over 1.5-fold of normal value. Severe cardiac dysfunction on echocardiogram or the grade of heart function over Ⅲ grade. History of prior stroke with mRS ≥2. Complicated with atrial fibrillation. Severe stroke as assessed by appropriate imaging techniques (eg. massive cerebral infarction including more than one lobe of brain or over 1/3 of blood-supply area of middle cerebral artery). Prior disable patients. Hemorrhagic tendency or recent severe or dangerous bleeding in 3 months. Suspected addicted into alcohol or drug abuse. With severe complications that would make the condition more complicated assessed by the investigator. Woman with pregnancy, lactation or positive result of pregnancy test, or women who want to be pregnant in recent 6 months. Woman who is under menstrual period. Patient who is participating in other trials or has been participated in other trials in recent 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Danhong injection<br>Based on the standard medical care, 40ml of Danhong injection, added into 250ml of 0.9% saline, given by continuous IV infusion at 2.5ml/min within 2 hours. | Drug: Danhong injection<br>* A kind of injection made from two kind of Chinese herbs: Salvia miltiorrhiza and Safflower. 40ml Danhong injection added into 250ml 0.9% saline by an independent research nurse, sealed with brown bag in order to make the investigators and patients blinded, using brown infusion tube for infusion<br>Procedure: Standard medical care<br>* Standard medical care is in accordance with China Guideline for the diagnosis and treatment of acute ischemic stroke (2010), including medical care for vital signs, control of temperature, blood pressure and glucose, improving cerebral blood circulation, antiplatelet treatment and nutritional supportive care.<br>|
| Placebo Comparator: placebo<br>Based on the standard medical care, 40ml of 0.9% saline as the placebo, added into 250ml of 0.9% saline, given by continuous IV infusion at 2.5ml/min within 2 hours. | Procedure: Standard medical care<br>* Standard medical care is in accordance with China Guideline for the diagnosis and treatment of acute ischemic stroke (2010), including medical care for vital signs, control of temperature, blood pressure and glucose, improving cerebral blood circulation, antiplatelet treatment and nutritional supportive care.<br>Drug: placebo<br>* 0.9% saline added into 250ml 0.9% saline by an independent research nurse, sealed with brown bag in order to make the investigators and patients blinded, using brown infusion tube for infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin Scale 0-1 (favourable outcome) at Day 90 |  | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Score of effect on symptoms of Xueyue Zheng(Blood Stasis syndrome) |  | Day 0, Day7, Day 14, Day 30, Day 60, Day 90 | 
| Barthel Index score ≥90 |  | Day 0, Day7, Day 14, Day 30, Day 60, Day 90 | 
| NIH stroke scale(NIHSS) | The improvement of the NIHSS score ≥4 or the NIHSS score of 0 to 1 | Day 0, Day7, Day 14, Day 30, Day 60, Day 90 | 
| EQ-5D scale |  | Day 0, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| Global disability on mRS at Day 90. | The proportion of patients with mRS ≥3 at Day 90. | Day 90 | 
| Incidence of new-onset major vascular events in 90 days | Major adverse vascular events include ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction and vascular-related death. | Day 90 | 
| Overall mortality at day 90 |  | Day 90 | 
| Incidence of severe hemorrhages in 90 days | The definition of Severe hemorrhages is in accordance with the GUSTO bleeding criteria, including fatal intracranial hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH) or which could result in substantial hemodynamic compromise requiring treatment. | Day 90 | 
| Incidence of moderate hemorrhages in 90 days | The definition of moderate hemorrhages is in accordance with the GUSTO bleeding criteria, which requires blood transfusion but not results in hemodynamic compromise. | Day 90 | 
| Documentation of adverse events (AEs) and serious AEs |  | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Ischemic Stroke, Randomized Controlled Trial, Traditional Chinese Medicine