Danhong Injection in the Treatment of Acute Ischemic Stroke

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

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

Study Overview

• Status: Completed
• Conditions: Acute Stroke
• Intervention / Treatment: Drug: Danhong injection; Procedure: Standard medical care; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 1503
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100034
    • Peking University First Hospital
  • Beijing, China, 100050
    • Tiantan Hospital Affiliated to Capital Medical University
  • Beijing, China, 100053
    • Xuan Wu hospital affiliated to Capital Medical University
  • Beijing
    • Beijing, Beijing, China, 100088
      • The Second Artillery General Hospital Of Chinese People's Liberation Army
  • Chongqing
    • Chongqing, Chongqing, China, 400037
      • Xinqiao Hospital of Third Military Medical University
    • Chongqing, Chongqing, China, 404000
      • Chongqing Three Gorges Central Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510317
      • Guangdong No.2 Provincial People's Hospital
    • Guangzhou, Guangdong, China, 510813
      • Guangzhou hospital of integrated Chinese and Western medicine
    • Shenzhen, Guangdong, China, 518028
      • The Second People's Hospital of Shenzhen
  • Hebei
    • Baoding, Hebei, China, 072750
      • The Second Central Hospital of Baoding City
    • Chengde, Hebei, China, 067000
      • Affiliated Hospital of Chengde Medical University
    • Handan, Hebei, China, 056001
      • HanDan Central Hospital
  • Helongjiang
    • Harbin, Helongjiang, China, 150001
      • The Second Affiliated Hopital of Harbin Medical University
  • Henan
    • Luoyang, Henan, China, 471003
      • The Second Chinese Medical Hospital of Luoyang City
    • Nanyang, Henan, China, 473007
      • Nanyang T.C.M. Hospital
    • Nanyang, Henan, China, 473065
      • Nanshi Hospital of Nanyang
    • Zhengzhou, Henan, China, 450000
      • The First Affiliated Hospital of Henan University of T.C.M.
    • Zhengzhou, Henan, China, 450003
      • People's Hospital of Zhengzhou
    • Zhengzhou, Henan, China, 450006
      • Zhengzhou No.7 People's Hospital
    • Zhoukou, Henan, China, 466099
      • Zhoukou Hospital of T.C.M.
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Zhongnan Hospital of Wuhan University
    • Wuhan, Hubei, China, 430060
      • Renmin Hospital of Wuhan University
    • Wuhan, Hubei, China, 430014
      • The Central Hospital of Wuhan
    • Wuhan, Hubei, China, 430033
      • Zhongshan Hospital of Hubei Province
    • Wuhan, Hubei, China, 430050
      • Fifth Hospital in Wuhan
    • Wuhan, Hubei, China, 430064
      • Tianyou Hospital Affiliated to Wuhan University of Science & Technology
    • Wuhan, Hubei, China, 430399
      • Huangpi District Hospital of T.C.M.
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central-South University
    • Changsha, Hunan, China, 410004
      • Changsha Central Hospital
    • Changsha, Hunan, China, 410005
      • The First Hospital of Changsha
    • Changsha, Hunan, China, 410007
      • The Second People's Hospital of Hunan Province
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hospital
    • Nanjing, Jiangsu, China, 210001
      • Nanjing Hospital of T.C.M.
    • Nanjing, Jiangsu, China, 210003
      • The Second Affiliated Hospital of Nanjing Medical University
  • Jilin
    • Changchun, Jilin, China, 130021
      • Jilin Province People's Hospital
    • Changchun, Jilin, China, 130021
      • The Affiliated Hopital to Changchun University of Chinese Medicine
    • Changchun, Jilin, China, 130021
      • The First Hospital Affiliated to Jilin University
    • Changchun, Jilin, China, 130033
      • China-Japan Union Hospital of Jilin University
    • Changchun, Jilin, China, 130041
      • The Second Hospital of Jilin University
    • Liaoyuan, Jilin, China, 136299
      • Liaoyuan Traditional Chinese Medical Hospital
  • Liaoning
    • Anshan, Liaoning, China, 114001
      • Anshan Central Hospital
    • Dalian, Liaoning, China, 116001
      • Affiliated Zhongshan Hospital Of Dalian University
    • Dandong, Liaoning, China, 118015
      • Dandong First Hospital
    • Panjin, Liaoning, China, 124013
      • Panjin Central Hospital
    • Shenyang, Liaoning, China, 110003
      • People's Liberation Army No.202 Hospital
    • Shenyang, Liaoning, China, 110016
      • The General Hospital of Shenyang Military
    • Shenyang, Liaoning, China, 110046
      • People's Liberation Army No.463 Hospital
  • Neimenggu
    • Chifeng, Neimenggu, China, 024005
      • Affiliated Hospital of Chifeng University
  • Shanxi
    • Luliang, Shanxi, China, 032299
      • Fenyang Hospital of Shanxi Province
    • Taiyuan, Shanxi, China, 030001
      • The Second Affiliated Hospital to Shanxi Medical University
    • Xi'an, Shanxi, China, 710003
      • Shanxi Province Hospital of T.C.M.
    • Xi'an, Shanxi, China, 710054
      • The PLA Fourth Fifty-one Hospital
    • Xi'an, Shanxi, China, 710068
      • Shanxi Provincial People's Hospital
    • Xianyang, Shanxi, China, 712000
      • Affiliated Hospital of Shanxi University of Chinese Medicine
    • Xianyang, Shanxi, China, 712000
      • The Second Affiliated Hospital of Shanxi University of T.C.M.
  • Sichuan
    • Chengdu, Sichuan, China, 610072
      • Teaching Hospital of Chengdu University of Traditional Chinese Medicine
    • Chengdu, Sichuan, China, 610500
      • The First Affiliated Hopital of Chengdu Medical College
  • Tianjin
    • Tianjin, Tianjin, China, 300193
      • First Teaching Hospital of Tianjin University of Traditional Chinese Medicine
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310014
      • Zhejiang Provincial People's Hospital
    • Hangzhou, Zhejiang, China, 310005
      • Xin Hua Hospital of Zhejiang Province
    • Hangzhou, Zhejiang, China, 310006
      • Zhejiang Provincial Hospital of T.C.M.
    • Huzhou, Zhejiang, China, 313003
      • Huzhou Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Danhong injection; 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; 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; Procedure: Standard medical care; 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.
Placebo Comparator: placebo; 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; 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.; Drug: placebo; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
The changes on the profiles of micro-RNA in 96 patients selected from certain centers	Day 0, Day 14, Day 90
The changes on the expression profiles of mRNA in 96 patients selected from certain centers	Day 0, Day 14, Day 90

Collaborators and Investigators

• Sponsor: China Academy of Chinese Medical Sciences
• Collaborators: China Food and Drug Administration
• Investigators: Principal Investigator: Xing-quan Zhao, Professor, Beijing Tiantan Hospital

Publications and helpful links

General Publications

• Li B, Wang Y, Lu J, Liu J, Yuan Y, Yu Y, Wang P, Zhao X, Wang Z. Evaluating the effects of Danhong injection in treatment of acute ischemic stroke: study protocol for a multicenter randomized controlled trial. Trials. 2015 Dec 9;16:561. doi: 10.1186/s13063-015-1076-4.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2013
• Primary Completion (Actual): March 10, 2019
• Study Completion (Actual): March 27, 2019

Study Registration Dates

• First Submitted: August 29, 2012
• First Submitted That Met QC Criteria: August 29, 2012
• First Posted (Estimate): August 31, 2012

Study Record Updates

• Last Update Posted (Actual): June 8, 2022
• Last Update Submitted That Met QC Criteria: June 6, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Traditional Chinese Medicine; Acute Ischemic Stroke
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: DH20120423