Danhong Injection in the Treatment of Chronic Stable Angina

A Randomized, Multi-center, Double-blind, Placebo-controlled Trial of Danhong Injection in the Treatment of Chronic Stable Angina

The purpose of this study is to evaluate the effect of Danhong Injection on the relief of angina with the use of the Seattle Angina Questionnaire among patients with stable angina patients

Study Overview

• Status: Completed
• Conditions: Chronic Stable Angina
• Intervention / Treatment: Drug: Danhong injection; Other: Standard medical care; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 920
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital
    • Beijing, Beijing, China, 100053
      • Guang'anmen Hospital, China Academy of Chinese Medical Sciences
    • Beijing, Beijing, China, 100053
      • Xuan Wu hospital affiliated to Capital Medical University
    • Beijing, Beijing, China, 100078
      • Dongfang Hospital
    • Beijing, Beijing, China, 100853
      • Chinese PLA General Hospital(301 Hospital)
  • Chongqing
    • Chongqing, Chongqing, China, 400011
      • Chongqing Traditional Chinese Medicine Hopital
    • Chongqing, Chongqing, China, 400014
      • The Third People's Hospital of Chongqing
  • Heilongjiang
    • Ha'erbin, Heilongjiang, China, 150009
      • The Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine
    • Ha'erbin, Heilongjiang, China, 150040
      • The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine
  • Henan
    • Zhengzhou, Henan, China, 450000
      • The First Affiliated Hospital of Henan University of T.C.M.
    • Zhengzhou, Henan, China, 450053
      • People's Hospital of Zhengzhou
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Zhongnan Hospital of Wuhan University
    • Wuhan, Hubei, China, 430060
      • Renmin Hospital of Wuhan University
    • Wuhan, Hubei, China, 430061
      • Hubei Provincial Hospital of T.C.M.
  • Hunan
    • Changsha, Hunan, China, 410004
      • Changsha Central Hospital
    • Changsha, Hunan, China, 410005
      • The First Hospital of Changsha
    • Changsha, Hunan, China, 410005
      • The Second Affiliated Hospital to Hunan University of Chinese Medicine
  • Jilin
    • Changchun, Jilin, China, 130021
      • Jilin Province People's Hospital
    • Changchun, Jilin, China, 130021
      • The Affiliated Hospital To Changchun University of Chinese Medicine
  • Liaoning
    • Dalian, Liaoning, China, 116001
      • Affiliated Zhongshan Hospital Of Dalian University
  • Shanghai
    • Shanghai, Shanghai, China, 200065
      • Shanghai Tongji Hospital
    • Shanghai, Shanghai, China, 200072
      • Shanghai Tenth People's Hospital
    • Shanghai, Shanghai, China, 200071
      • Shanghai Municipal Hospital of Traditional Chinese Medicine
  • Shanxi
    • Taiyuan, Shanxi, China, 030001
      • The First Affiliated Hospital to Shanxi Medical University
    • Xi'an, Shanxi, China, 710068
      • Shanxi Provincial People's Hospital
    • Xi'an, Shanxi, China, 710001
      • Xi'an City Hospital of T.C.M.
    • Xi'an, Shanxi, China, 710003
      • Shanxi Province Hosptial of T.C.M.
    • Xianyang, Shanxi, China, 712000
      • Affiliated Hospital of Shanxi University of Chinese Medicine
  • Sichuan
    • Chengdu, Sichuan, China, 610017
      • Chengdu Sencond People's Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300150
      • Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Xin Hua Hospital of Zhejiang Province

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.
• Patients with clinical diagnosis of chronic stable angina and must meet one of the following conditions:1）Patients who have a history of myocardial infarction and ST-T changes;2）Stenosis of more than 50% in at least one major epicardial coronary artery shown by Coronary Angiograph or CT Angiography; 3）Patients with coronary heart disease were determined by radionuclide angiocardiography.
• Clinical diagnosis of "Xueyu Zheng" (Blood Stasis Syndrome) as the scores of Chinese medicine symptoms scales of "Xueyu Zheng" in angina ≥ 15. The Chinese medicine symptoms scales of "Xueyu Zheng" is defined as following (1)chest pain-10, (2)chest distress-10, (3) palpitation-5, (4)purple or dark lip-5, (5) purple or dark tongue-5, (6) unsmooth pulse-5.
• Patients with moderate angina pectoris (The definition of "moderate angina pectoris " is in accordance with the Canadian Cardiovascular Society (CCS) grading of angina pectoris,which be classified to II or III.
• Patient is willing to participate voluntarily and to sign a written patient informed consent.

Exclusion Criteria:

• Woman with pregnancy, lactation or positive result of pregnancy test, or woman who is under menstrual period.
• Woman who disagree with contraception during treatment period
• Patients with severe complications that would make the condition more complicated assessed by the investigator, including liver or renal dysfunction, severe cardiopulmonary dysfunction, pulmonary hypertension, chronic obstructive pulmonary disease, a history of epilepsy or cerebral hemorrhage .
• Patients who were angina-free during the run-in period without taking any drug.
• Patients with myocardial infarction or Canadian Cardiovascular Society (CCS) grading of angina pectoris class IV within the preceding 3 months
• Patients with chest pain caused by other disease (e.g., acute myocardial infarction，severe neurosis，menopausal syndrome，hyperthyroidism).
• Patients with history of drug-induced bleeding or history of bleeding caused by warfarin.
• Patients with history of hematopoietic system diseases.
• Patients who had surgery within the past 4 weeks and have hemorrhagic tendency.
• Patients who is participating in other trials or has been participated in other trials in recent 3 months.
• Patients with history of allergy or suspected allergic to the drug.
• Patients who were suspected addicted into alcohol or drug abuse in the past 2 years.
• Patients with mental disorder.
• Patients who were unable to participate in the study as judged by investigator.
• Patients who were family members or relatives of the research center staffs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• 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; Other: Standard medical care; Standard medical care is in accordance with China Guideline for the diagnosis and treatment of Chronic Stable Angina (2007).
PLACEBO_COMPARATOR: Placebo; Based on the standard medical care, placebo was 40ml of 0.9% saline, added into 250ml of 0.9% saline, given by continuous IV infusion at 2.5ml/min within 2 hours.	Other: Standard medical care; Standard medical care is in accordance with China Guideline for the diagnosis and treatment of Chronic Stable Angina (2007).; 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	Measure Description	Time Frame
The proportion of patients in each treatment group who had clinically significant change as defined by the angina-frequency score on the Seattle Angina Questionnaire at day 30	Seattle Angina Questionnaire, a 19-item questionnaire that quantifies physical limitations due to angina, any recent change in the severity of angina, the frequency of angina, satisfaction with treatment, and quality of life. Scores range from 0 to 100; higher scores indicate better health status.With a score of 20 or more on the angina-frequency scale indicating that the patient was clinically significant change.	Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Total score of symptoms questionnaire of TCM	The symptoms questionnaire of TCM consists of 6 symptoms that described in traditional Chinese medicine, including chest pain, chest distress, palpitation, dark-purple lip, dark-purple tongue and unsmooth pulse. Each symptom was assessed by the Visual Analogue Scale（VAS），where a higher score meant higher severity.	Day 0, Day 7, Day 14, Day 30, Day 60, Day 90
The proportion of patients in each treatment group who had clinically significant changes in the other four Seattle Angina Questionnaire scales （The physical limitation, angina stability, treatment satisfaction, and quality of life）	We defined clinical significant changes as a difference of 8 points or more on the physical-limitation scale, 25 or more on the angina-stability scale, 12 or more on the treatment-satisfaction scale, or 16 or more on the quality-of-life scale.	Day 0, Day 7, Day 14, Day 30, Day 60, Day 90
The frequency of anginal attack every week	The frequency of anginal attack was recorded by the patients with the use of the diary cards which will be collected from the run-in period (Day -7) to the end of follow-up (Day 90).	Day-7 (if exist), Day 0, Day 7, Day 14, Day 30, Day 60, Day 90
Canadian Cardiovascular Society (CCS) grading of angina pectoris		Day 0, Day 7, Day 14, Day 30, Day 60, Day 90
Consumption of Short-acting Nitrates		Day -7( if exist), Day 0, Day 7, Day 14, Day 30, Day 60, Day 90
Change in the electrocardiogram (EKG)		Day 0, Day 7, Day 14, Day 30, Day 60, Day 90
Changes in the Serum Lipid, the high-sensitivity C-Reactive Protein(hs-CRP) and the Platelet Aggregation Rate		Day 0, Day 14
Overall mortality in 90 days		Day 90

Other Outcome Measures

Outcome Measure	Time Frame
The profiles of micro-RNA in 60 patients selected from certain centers	Day 0, Day 14, Day 90
The profiles of mRNA in 60 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: Yun-dai Chen, Professor, Chinese PLA General Hospital(301 Hospital)

Publications and helpful links

General Publications

• Liu J, Li DD, Dong W, Liu YQ, Wu Y, Tang DX, Zhang FC, Qiu M, Hua Q, He JY, Li J, Du B, Du TH, Niu LL, Jiang XJ, Cui B, Chen JB, Wang YG, Wang HR, Yu Q, He J, Mao YL, Bin XF, Deng Y, Tian YD, Han QH, Liu DJ, Duan LQ, Zhao MJ, Zhang CY, Dai HY, Li ZH, Xiao Y, Hu YZ, Huang XY, Xing K, Jiang X, Liu CF, An J, Li FC, Tao T, Jiang JF, Yang Y, Dong YR, Zhang L, Fu G, Li Y, Huang SW, Dou LP, Sun LJ, Zhao YQ, Li J, Xia Y, Liu J, Liu F, He WJ, Li Y, Tan JC, Lin Y, Zhou YB, Yang JF, Ma GQ, Chen HJ, Liu HP, Liu ZW, Liu JX, Luo XJ, Bin XH, Yu YN, Dang HX, Li B, Teng F, Qiao WM, Zhu XL, Chen BW, Chen QG, Shen CT, Wang YY, Chen YD, Wang Z. Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial. Signal Transduct Target Ther. 2021 Sep 1;6(1):329. doi: 10.1038/s41392-021-00741-x.
• Wang PQ, Li DD, Dong W, Liu J, Yu YN, Shen CT, Chen QG, Chen BW, Chen YD, Wang Z. Danhong injection in the treatment of chronic stable angina: study protocol for a randomized controlled trial. Trials. 2015 Oct 21;16:474. doi: 10.1186/s13063-015-0998-1.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (ACTUAL): October 1, 2016
• Study Completion (ACTUAL): October 1, 2016

Study Registration Dates

• First Submitted: September 5, 2012
• First Submitted That Met QC Criteria: September 6, 2012
• First Posted (ESTIMATE): September 7, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): October 12, 2016
• Last Update Submitted That Met QC Criteria: October 11, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Traditional Chinese Medicine; Chronic Stable Angina
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Angina, Stable
• Other Study ID Numbers: DH20120703