<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03027375</url>
  </required_header>
  <id_info>
    <org_study_id>2016-ZXFZJJ-003</org_study_id>
    <nct_id>NCT03027375</nct_id>
  </id_info>
  <brief_title>Evaluating the Safety and Efficacy of Qishen Granules Among Patients With Chronic Heart Failure</brief_title>
  <official_title>Evaluating the Safety and Efficacy of Qishen Granules Among Patients With Chronic Heart Failure: Study Protocol for a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing University of Chinese Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>China-Japan Friendship Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zhengzhou Hospital of Traditional Chinese Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing Anzhen Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Beijing University of Chinese Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial will assess the efficacy and safety of QSG in CHF.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Chronic heart failure(CHF), the final stage of various cardiovascular diseases,&#xD;
      is a major public health problem associated with significant hospitalization rates,&#xD;
      mortality, and huge health care costs, despite advances in the treatment and management of&#xD;
      heart failure and heart failure related risk factors. Qishen granules(QSG), a Chinese herbal&#xD;
      formula, is widely used by traditional chinese medicine(TCM) practitioners to treat CHF.&#xD;
      Several animal experimental studies have showed that QSG can significantly relieve the heart&#xD;
      failure symptoms of CHF rat models. However, there is yet no standard clinical trial to&#xD;
      assess that. Thus, the investigators are conducting this study to evaluate the efficacy and&#xD;
      safety of QSG in a large, varied population.&#xD;
&#xD;
      Methods/Design: This study is designed as a randomized, multi-center, placebo-controlled,&#xD;
      double-blind , parallel-group clinical trial. An established total of 200 patients with CHF&#xD;
      will be recruited and randomly allocated to either the QSG treatment group or the placebo&#xD;
      group (a 1:1 ratio). The patients will receive QSG or placebo granules twice daily for 12&#xD;
      weeks. The primary endpoint is the reduction or percent change in the plasma N-terminal&#xD;
      pro-B-type natriuretic peptide(NT-proBNP) level during 12 weeks of treatment. The secondary&#xD;
      endpoints consist of composite cardiac events (CCEs), New York Heart Association (NYHA)&#xD;
      functional classification, 6-minute walking distance (6MWD), Left ventricular ejection&#xD;
      fraction, patient quality of life and TCM syndrome integral scale.&#xD;
&#xD;
      Discussion: This trial will assess the efficacy and safety of QSG in CHF.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 31, 2017</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>the reduction or percent change in the plasma N-terminal pro-B-type natriuretic peptide</measure>
    <time_frame>12weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>composite cardiac events</measure>
    <time_frame>4weeks,8weeks,12weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>New York Heart Association (NYHA) functional classification</measure>
    <time_frame>4weeks,8weeks,12weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6-minute walking distance</measure>
    <time_frame>4weeks,8weeks,12weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left ventricular ejection fraction</measure>
    <time_frame>12weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chronic Heart Failure Quality of Life Scale of Integrated Chinese and Western Medicine</measure>
    <time_frame>4weeks,8weeks,12weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TCM syndrome integral scale</measure>
    <time_frame>4weeks,8weeks,12weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Heart Failure</condition>
  <condition>Cardiovascular Diseases</condition>
  <arm_group>
    <arm_group_label>Qishen granules</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The QSG treatment group will receive Qishen granules (13.6 g/pouch, twice per day-30 minutes after breakfast and dinner-for 12 weeks; dosage based on the requirements of Pharmacopoeia of the People's Republic of China).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo granules</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo group will receive placebo granules (13.6 g/pouch, twice per day-30 minutes after breakfast and dinner-for 12 weeks).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Qishen Granules</intervention_name>
    <description>The QSG are manufactured by Beijing tcmages Pharmaceutical Co., Ltd. (Beijing, China), a company that has obtained Chinese Good Manufacturing Practice for Pharmaceutical Products certification. All the ingredients have been approved by the Chinese Ministry of Food and Drug Safety. 13.6 grams (dry weight) of granules consist of six herbs: Astragalus membranaceus (Fisch.) Bge. var. Mongolicus (Bge.) Hsiao (6g), Salvia miltiorrhiza Bge. (1.5g), Lonicera japonica Thunb. (2g), Scrophularia ningpoensis Hemsl. (2g), Aconitum carmichaeli Debx. (0.9g), and Glycyrrhiza uralensis Fisch. (1.2g).</description>
    <arm_group_label>Qishen granules</arm_group_label>
    <other_name>Yixin Jiedu formula</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The placebo is manufactured by Beijing tcmages Pharmaceutical Co., Ltd. (Beijing, China) as well, following the Specification for processing Chinese medicine in Beijing. The placebo granules are similar in appearance, taste, and scent to the Qishen granules.</description>
    <arm_group_label>placebo granules</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. age between 18 and 75 years;&#xD;
&#xD;
          2. clinical findings of CHF for at least 3 months prior to screening;&#xD;
&#xD;
          3. CHF caused by coronary heart disease and hypertension, which is diagnosed according to&#xD;
             the Chinese guidelines published in 2014 for the diagnosis and management of CHF;&#xD;
&#xD;
          4. clinically stable condition with an NYHA functional class of II to III and an optimal&#xD;
             medical treatment with a fixed dosage for at least 2 weeks;&#xD;
&#xD;
          5. a documented left ventricular ejection fraction (LVEF) ≤40% and a serum NT-proBNP&#xD;
             level ≥450 pg/ml;&#xD;
&#xD;
          6. CHF of Qi deficiency and blood stasis syndrome;&#xD;
&#xD;
          7. provision of written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. CHF complicated with severe valvular disease, congenital heart disease, pericardial&#xD;
             disease, cardiomyopathy, unstable angina, acute myocardial infarction(in recent 4&#xD;
             weeks), cardiogenic shock, acute myocarditis, infective endocarditis, uncontrolled&#xD;
             severe cardiac arrhythmia with hemodynamic changes;&#xD;
&#xD;
          2. pulmonary heart disease, pulmonary hypertension caused by acute or chronic pulmonary&#xD;
             embolism or cerebral apoplexy in recent 6 months;&#xD;
&#xD;
          3. severe hepatic inadequacy with alanine aminotransferase or alkaline phosphatase levels&#xD;
             &gt;2 times the upper normal limit, renal inadequacy with a creatinine clearance rate&gt;20%&#xD;
             or a serum creatinine level&gt;3mg/dl (&gt;265μmol/L), severe electrolyte imbalance, severe&#xD;
             hematologic disease, malignant tumor, diabetes mellitus with severe complications, or&#xD;
             severe endocrine diseases such as hyperthyroidism and hypothyroidism;&#xD;
&#xD;
          4. acute infection confirmed by any one of the following 3 tips: 1) fever; 2) a white&#xD;
             blood cell count&gt;10×109/L and a percentage of neutrophils&gt;85%; 3) shadows on chest&#xD;
             X-ray;&#xD;
&#xD;
          5. uncontrolled blood pressure or fibrosis in other organs;&#xD;
&#xD;
          6. CHF of yin deficiency according to TCM syndrome differentiation;&#xD;
&#xD;
          7. pregnancy or breastfeeding;&#xD;
&#xD;
          8. psychiatric or infectious disease;&#xD;
&#xD;
          9. patients who have participated in other clinical trials in the past two months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wei Wang, Doctor</last_name>
    <role>Study Chair</role>
    <affiliation>Beijing University of Chinese Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Huihui Zhao, Doctor</last_name>
    <role>Study Director</role>
    <affiliation>Beijing University of Chinese Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jinping Wang, Master</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beijing University of Chinese Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jinping Wang, Master</last_name>
    <phone>13810689802</phone>
    <email>wjpbucm@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>China-Japan Friendship Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100029</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jinping Wang, doctor</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Li X, Zhang J, Huang J, Ma A, Yang J, Li W, Wu Z, Yao C, Zhang Y, Yao W, Zhang B, Gao R; Efficacy and Safety of Qili Qiangxin Capsules for Chronic Heart Failure Study Group. A multicenter, randomized, double-blind, parallel-group, placebo-controlled study of the effects of qili qiangxin capsules in patients with chronic heart failure. J Am Coll Cardiol. 2013 Sep 17;62(12):1065-1072. doi: 10.1016/j.jacc.2013.05.035. Epub 2013 Jun 7.</citation>
    <PMID>23747768</PMID>
  </reference>
  <reference>
    <citation>General Assembly of the World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. J Am Coll Dent. 2014 Summer;81(3):14-8.</citation>
    <PMID>25951678</PMID>
  </reference>
  <reference>
    <citation>Switula D. Principles of good clinical practice (GCP) in clinical research. Sci Eng Ethics. 2000 Jan;6(1):71-7. doi: 10.1007/s11948-000-0025-z.</citation>
    <PMID>11273440</PMID>
  </reference>
  <results_reference>
    <citation>van Riet EE, Hoes AW, Wagenaar KP, Limburg A, Landman MA, Rutten FH. Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time. A systematic review. Eur J Heart Fail. 2016 Mar;18(3):242-52. doi: 10.1002/ejhf.483. Epub 2016 Jan 4.</citation>
    <PMID>26727047</PMID>
  </results_reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>January 16, 2017</study_first_submitted>
  <study_first_submitted_qc>January 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <last_update_submitted>October 6, 2017</last_update_submitted>
  <last_update_submitted_qc>October 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beijing University of Chinese Medicine</investigator_affiliation>
    <investigator_full_name>Wei Wang</investigator_full_name>
    <investigator_title>Vice-President</investigator_title>
  </responsible_party>
  <keyword>chronic heart failure</keyword>
  <keyword>traditional Chinese medicine</keyword>
  <keyword>Qishen granules</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Cardiovascular Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03027375
org study id: 2016-ZXFZJJ-003
nct id: NCT03027375
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This trial will assess the efficacy and safety of QSG in CHF.
Background: Chronic heart failure(CHF), the final stage of various cardiovascular diseases,
      is a major public health problem associated with significant hospitalization rates,
      mortality, and huge health care costs, despite advances in the treatment and management of
      heart failure and heart failure related risk factors. Qishen granules(QSG), a Chinese herbal
      formula, is widely used by traditional chinese medicine(TCM) practitioners to treat CHF.
      Several animal experimental studies have showed that QSG can significantly relieve the heart
      failure symptoms of CHF rat models. However, there is yet no standard clinical trial to
      assess that. Thus, the investigators are conducting this study to evaluate the efficacy and
      safety of QSG in a large, varied population.

      Methods/Design: This study is designed as a randomized, multi-center, placebo-controlled,
      double-blind , parallel-group clinical trial. An established total of 200 patients with CHF
      will be recruited and randomly allocated to either the QSG treatment group or the placebo
      group (a 1:1 ratio). The patients will receive QSG or placebo granules twice daily for 12
      weeks. The primary endpoint is the reduction or percent change in the plasma N-terminal
      pro-B-type natriuretic peptide(NT-proBNP) level during 12 weeks of treatment. The secondary
      endpoints consist of composite cardiac events (CCEs), New York Heart Association (NYHA)
      functional classification, 6-minute walking distance (6MWD), Left ventricular ejection
      fraction, patient quality of life and TCM syndrome integral scale.

      Discussion: This trial will assess the efficacy and safety of QSG in CHF.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: the reduction or percent change in the plasma N-terminal pro-B-type natriuretic peptide
time frame: 12weeks
measure: composite cardiac events
time frame: 4weeks,8weeks,12weeks
measure: New York Heart Association (NYHA) functional classification
time frame: 4weeks,8weeks,12weeks
measure: 6-minute walking distance
time frame: 4weeks,8weeks,12weeks
measure: Left ventricular ejection fraction
time frame: 12weeks
measure: Chronic Heart Failure Quality of Life Scale of Integrated Chinese and Western Medicine
time frame: 4weeks,8weeks,12weeks
measure: TCM syndrome integral scale
time frame: 4weeks,8weeks,12weeks
arm group label: Qishen granules
arm group type: Experimental
description: The QSG treatment group will receive Qishen granules (13.6 g/pouch, twice per day-30 minutes after breakfast and dinner-for 12 weeks; dosage based on the requirements of Pharmacopoeia of the People's Republic of China).
arm group label: placebo granules
arm group type: Placebo Comparator
description: The placebo group will receive placebo granules (13.6 g/pouch, twice per day-30 minutes after breakfast and dinner-for 12 weeks).
intervention type: Drug
intervention name: Qishen Granules
description: The QSG are manufactured by Beijing tcmages Pharmaceutical Co., Ltd. (Beijing, China), a company that has obtained Chinese Good Manufacturing Practice for Pharmaceutical Products certification. All the ingredients have been approved by the Chinese Ministry of Food and Drug Safety. 13.6 grams (dry weight) of granules consist of six herbs: Astragalus membranaceus (Fisch.) Bge. var. Mongolicus (Bge.) Hsiao (6g), Salvia miltiorrhiza Bge. (1.5g), Lonicera japonica Thunb. (2g), Scrophularia ningpoensis Hemsl. (2g), Aconitum carmichaeli Debx. (0.9g), and Glycyrrhiza uralensis Fisch. (1.2g).
arm group label: Qishen granules
other name: Yixin Jiedu formula
intervention type: Drug
intervention name: Placebo
description: The placebo is manufactured by Beijing tcmages Pharmaceutical Co., Ltd. (Beijing, China) as well, following the Specification for processing Chinese medicine in Beijing. The placebo granules are similar in appearance, taste, and scent to the Qishen granules.
arm group label: placebo granules
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Wei Wang, Doctor
role: Study Chair
affiliation: Beijing University of Chinese Medicine
last name: Huihui Zhao, Doctor
role: Study Director
affiliation: Beijing University of Chinese Medicine
last name: Jinping Wang, Master
role: Principal Investigator
affiliation: Beijing University of Chinese Medicine
last name: Jinping Wang, Master
phone: 13810689802
email: wjpbucm@163.com
facility: 
status: Recruiting
contact: 
country: China
citation: Li X, Zhang J, Huang J, Ma A, Yang J, Li W, Wu Z, Yao C, Zhang Y, Yao W, Zhang B, Gao R; Efficacy and Safety of Qili Qiangxin Capsules for Chronic Heart Failure Study Group. A multicenter, randomized, double-blind, parallel-group, placebo-controlled study of the effects of qili qiangxin capsules in patients with chronic heart failure. J Am Coll Cardiol. 2013 Sep 17;62(12):1065-1072. doi: 10.1016/j.jacc.2013.05.035. Epub 2013 Jun 7.
PMID: 23747768
citation: General Assembly of the World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. J Am Coll Dent. 2014 Summer;81(3):14-8.
PMID: 25951678
citation: Switula D. Principles of good clinical practice (GCP) in clinical research. Sci Eng Ethics. 2000 Jan;6(1):71-7. doi: 10.1007/s11948-000-0025-z.
PMID: 11273440
citation: van Riet EE, Hoes AW, Wagenaar KP, Limburg A, Landman MA, Rutten FH. Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time. A systematic review. Eur J Heart Fail. 2016 Mar;18(3):242-52. doi: 10.1002/ejhf.483. Epub 2016 Jan 4.
PMID: 26727047
responsible party type: Principal Investigator
investigator affiliation: Beijing University of Chinese Medicine
investigator full name: Wei Wang
investigator title: Vice-President
mesh term: Heart Failure
mesh term: Cardiovascular Diseases
sharing ipd: No