<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/NCT04493840</url>
  </required_header>
  <id_info>
    <org_study_id>2019013</org_study_id>
    <nct_id>NCT04493840</nct_id>
  </id_info>
  <brief_title>Randomized Evaluation of Shenfu Injection to Reduce Myocardial Injury</brief_title>
  <acronym>RESTORE</acronym>
  <official_title>Effect of Shenfu Injection on Myocardial Injury in Patients With Acute ST Segment Elevation Myocardial Infarction After Primary Percutaneous Coronary Intervention: A Multicenter, Randomized, Double-Blinded, Parallel-Group, Placebo-Controlled Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing Anzhen Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing Anzhen Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to evaluate whether perioperative use of Shenfu Injection, as compared to&#xD;
      placebo, could reduce infarct size assessed by cardiac magnetic resonance (CMR) in patients&#xD;
      with acute anterior ST-segment elevation myocardial infarction (STEMI) undergoing primary&#xD;
      percutaneous coronary intervention (PCI).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Shenfu injection is a traditional Chinese medicine formulation containing ginseng (Panax;&#xD;
      family: Araliaceae) and aconite (Radix aconiti lateralis preparata, Aconitum carmichaeli&#xD;
      Debx; family: Ranunculaceae) with Ginsenosides and aconite alkaloids as the main active&#xD;
      ingredients. Its quality is strictly controlled in compliance with the standard of the China&#xD;
      Ministry of Public Health (official approval code: certification number Z20043117; No.&#xD;
      110804, Ya'an, China). Animal studies have shown that Shenfu injection has protective effects&#xD;
      against reperfusion injury through multiple pharmacologic effects, including scavenging free&#xD;
      radicals, inhibiting inflammatory mediators, suppressing cell apoptosis, and inhibiting&#xD;
      calcium overload. However, few data are available regarding its efficacy in humans. We aimed&#xD;
      to determine whether perioperative use of Shenfu injection, as compared to placebo, might&#xD;
      reduce infarct size in patients with STEMI undergoing primary PCI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 30, 2020</start_date>
  <completion_date type="Anticipated">August 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2022</primary_completion_date>
  <phase>Phase 4</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>Infarct size (% of left ventricular mass)</measure>
    <time_frame>5±2 days after PCI</time_frame>
    <description>Infarct size was assessed by performing CMR imaging at 5±2 days after PCI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Microvascular obstruction (% of left ventricular mass)</measure>
    <time_frame>5±2 days after PCI</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intramyocardial hemorrhage (% of left ventricular mass)</measure>
    <time_frame>5±2 days after PCI</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve (AUC) of creatine kinase isoenzyme (CK-MB)</measure>
    <time_frame>Immediately after admission (0 hour), and 6, 12, 18, 24, 48, and 72 hours after PCI</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of cardiac troponin I</measure>
    <time_frame>Immediately after admission (0 hour), and 6, 12, 18, 24, 48, and 72 hours after PCI</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak value of CK-MB and cTnI</measure>
    <time_frame>72 hours after PCI</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ST segment resolution (%) according to ECG</measure>
    <time_frame>24 hours after PCI</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TIMI flow grade</measure>
    <time_frame>Immediately after PCI</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Corrected TIMI frame count (CTFC)</measure>
    <time_frame>Immediately after PCI</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TIMI myocardial perfusion grade (TMPG)</measure>
    <time_frame>Immediately after PCI</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Myocardial salvage index</measure>
    <time_frame>5±2 days after PCI</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area at risk (myocardial edema, % of left ventricular mass)</measure>
    <time_frame>5±2 days after PCI</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left ventricular end-diastolic volume (LVEDV)</measure>
    <time_frame>5±2 days after PCI</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left ventricular end-systolic volume (LVESV)</measure>
    <time_frame>5±2 days after PCI</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left ventricular ejection fraction (LVEF)</measure>
    <time_frame>5±2 days after PCI</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major adverse cardiovascular and cerebrovascular events (MACCE, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, emergency revascularization)</measure>
    <time_frame>30 days after PCI</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Individual events (including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, emergency revascularization, re-hospitalization for heart failure)</measure>
    <time_frame>30 days after PCI</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Slow flow and no flow</measure>
    <time_frame>Index procedure</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Malignant arrhythmia (ventricular fibrillation, ventricular tachycardia, etc.)</measure>
    <time_frame>Index procedure</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Value of high-sensitivity C-reactive protein (Hs-CRP)</measure>
    <time_frame>Immediately after admission (0 hour), and 24, 72 hours and 5 days after PCI</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Value of brain natriuretic peptide (BNP)</measure>
    <time_frame>Immediately after admission (0 hour), and 24, 72 hours and 5 days after PCI</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>The Myocardial Infarction Dimensional Assessment Scale (MIDAS)</measure>
    <time_frame>6 hours and 30 days after PCI</time_frame>
    <description>0 to 140 scores, higher scores mean worse outcome</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">326</enrollment>
  <condition>Myocardial Infarction</condition>
  <arm_group>
    <arm_group_label>Shenfu Injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>5% Glucose Injection</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Shenfu Injection</intervention_name>
    <description>80ml Shenfu Injection + 70ml 5% glucose injection, ivdrip, within 30 minutes before PCI and 1 to 5 days (once a day) after PCI (6 times in total). Drug titration time should be no less than 30 minutes.</description>
    <arm_group_label>Shenfu Injection</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5% Glucose Injection</intervention_name>
    <description>150 ml 5% glucose injection, ivdrip, within 30 minutes before PCI and 1 to 5 days (once a day) after PCI (6 times in total). Drug titration time should be no less than 30 minutes.</description>
    <arm_group_label>5% Glucose Injection</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥18 and &lt;75 years.&#xD;
&#xD;
          2. First-time acute anterior STEMI scheduled for primary PCI.&#xD;
&#xD;
          3. ST segment elevation in at least two contiguous precordial leads according to&#xD;
             electrocardiogram (&gt;30 min).&#xD;
&#xD;
          4. Symptoms onset ≤12 hours.&#xD;
&#xD;
          5. The presence of proximal or middle left anterior descending branch (LAD) occlusion&#xD;
             with pre-PCI TIMI flow 0 or 1 according to baseline coronary angiogram.&#xD;
&#xD;
          6. Written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Cardiogenic shock, serious heart failure (Killip class III or above), malignant&#xD;
             ventricular arrhythmia, or mechanical complications.&#xD;
&#xD;
          2. Post cardiopulmonary resuscitation (CPR) (including cardioversion).&#xD;
&#xD;
          3. Patients who have received thrombolytic therapy or upstream GPIIb/IIIa inhibitors&#xD;
             (GPI).&#xD;
&#xD;
          4. Uncontrolled hypertension (systolic BP ≥180 mm Hg or a diastolic BP ≥110 mmHg).&#xD;
&#xD;
          5. Prior myocardial infarction, PCI or coronary artery bypass graft.&#xD;
&#xD;
          6. Known severe hepatic insufficiency (AST/ALT &gt;3-fold the upper limit of normal value)&#xD;
             or known renal insufficiency.&#xD;
&#xD;
          7. Malignant tumor, lymphoma, HIV-positive, or cirrhosis with life expectancy &lt;1 year.&#xD;
&#xD;
          8. Patients with active bleeding, intracranial hemorrhage, major surgery or trauma within&#xD;
             1 months, or ischemic stroke or transient ischemic attack (TIA) within 6 months.&#xD;
&#xD;
          9. History of anemia (hemoglobin&lt;90g/L) or thrombocytopenia (thrombocyte&lt;100×109/L).&#xD;
&#xD;
         10. Patients who require simultaneous intervention of left main disease during primary PCI&#xD;
             or those with multi-vessel disease who plan to intervene in non-culprit vessels within&#xD;
             7 days (simultaneous or staged).&#xD;
&#xD;
         11. Scheduled for CABG within one month after randomization.&#xD;
&#xD;
         12. Pregnancy, lactation, or potentially fertile women.&#xD;
&#xD;
         13. Patients who have known to be allergic to Shenfu Injection or its components or&#xD;
             patients with serious adverse effect.&#xD;
&#xD;
         14. Patients with contraindication to CMR (metal foreign body in the body, claustrophobia,&#xD;
             etc.).&#xD;
&#xD;
         15. Participation in other clinical trial in recent 3 months.&#xD;
&#xD;
         16. Patients who cannot complete this trial or comply with the protocol.&#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_contact>
    <last_name>Shao-Ping Nie, MD, PhD</last_name>
    <phone>86-10-84005256</phone>
    <email>spnie@ccmu.edu.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Xiao Wang, MD</last_name>
    <phone>86-10-84005255</phone>
    <email>spaceeye123@126.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Beijing Anzhen Hospital, Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shao-Ping Nie, MD, PhD</last_name>
      <phone>86-10-84005256</phone>
      <email>spnie@ccmu.edu.cn</email>
    </contact>
    <contact_backup>
      <last_name>Xiao Wang, MD</last_name>
      <phone>86-10-84005255</phone>
      <email>spaceeye123@126.com</email>
    </contact_backup>
    <investigator>
      <last_name>Shao-Ping Nie, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>July 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>September 2, 2021</last_update_submitted>
  <last_update_submitted_qc>September 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beijing Anzhen Hospital</investigator_affiliation>
    <investigator_full_name>Shao-Ping Nie</investigator_full_name>
    <investigator_title>Professor of Medicine, Director, Emergency &amp; Critical Care Center</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>Infarction</mesh_term>
  </condition_browse>
  <!-- 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/NCT04493840
org study id: 2019013
nct id: NCT04493840
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study aims to evaluate whether perioperative use of Shenfu Injection, as compared to
      placebo, could reduce infarct size assessed by cardiac magnetic resonance (CMR) in patients
      with acute anterior ST-segment elevation myocardial infarction (STEMI) undergoing primary
      percutaneous coronary intervention (PCI).
Shenfu injection is a traditional Chinese medicine formulation containing ginseng (Panax;
      family: Araliaceae) and aconite (Radix aconiti lateralis preparata, Aconitum carmichaeli
      Debx; family: Ranunculaceae) with Ginsenosides and aconite alkaloids as the main active
      ingredients. Its quality is strictly controlled in compliance with the standard of the China
      Ministry of Public Health (official approval code: certification number Z20043117; No.
      110804, Ya'an, China). Animal studies have shown that Shenfu injection has protective effects
      against reperfusion injury through multiple pharmacologic effects, including scavenging free
      radicals, inhibiting inflammatory mediators, suppressing cell apoptosis, and inhibiting
      calcium overload. However, few data are available regarding its efficacy in humans. We aimed
      to determine whether perioperative use of Shenfu injection, as compared to placebo, might
      reduce infarct size in patients with STEMI undergoing primary PCI.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Infarct size (% of left ventricular mass)
time frame: 5±2 days after PCI
description: Infarct size was assessed by performing CMR imaging at 5±2 days after PCI
measure: Microvascular obstruction (% of left ventricular mass)
time frame: 5±2 days after PCI
measure: Intramyocardial hemorrhage (% of left ventricular mass)
time frame: 5±2 days after PCI
measure: Area under the curve (AUC) of creatine kinase isoenzyme (CK-MB)
time frame: Immediately after admission (0 hour), and 6, 12, 18, 24, 48, and 72 hours after PCI
measure: AUC of cardiac troponin I
time frame: Immediately after admission (0 hour), and 6, 12, 18, 24, 48, and 72 hours after PCI
measure: Peak value of CK-MB and cTnI
time frame: 72 hours after PCI
measure: ST segment resolution (%) according to ECG
time frame: 24 hours after PCI
measure: TIMI flow grade
time frame: Immediately after PCI
measure: Corrected TIMI frame count (CTFC)
time frame: Immediately after PCI
measure: TIMI myocardial perfusion grade (TMPG)
time frame: Immediately after PCI
measure: Myocardial salvage index
time frame: 5±2 days after PCI
measure: Area at risk (myocardial edema, % of left ventricular mass)
time frame: 5±2 days after PCI
measure: Left ventricular end-diastolic volume (LVEDV)
time frame: 5±2 days after PCI
measure: Left ventricular end-systolic volume (LVESV)
time frame: 5±2 days after PCI
measure: Left ventricular ejection fraction (LVEF)
time frame: 5±2 days after PCI
measure: Major adverse cardiovascular and cerebrovascular events (MACCE, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, emergency revascularization)
time frame: 30 days after PCI
measure: Individual events (including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, emergency revascularization, re-hospitalization for heart failure)
time frame: 30 days after PCI
measure: Slow flow and no flow
time frame: Index procedure
measure: Malignant arrhythmia (ventricular fibrillation, ventricular tachycardia, etc.)
time frame: Index procedure
measure: Value of high-sensitivity C-reactive protein (Hs-CRP)
time frame: Immediately after admission (0 hour), and 24, 72 hours and 5 days after PCI
measure: Value of brain natriuretic peptide (BNP)
time frame: Immediately after admission (0 hour), and 24, 72 hours and 5 days after PCI
measure: The Myocardial Infarction Dimensional Assessment Scale (MIDAS)
time frame: 6 hours and 30 days after PCI
description: 0 to 140 scores, higher scores mean worse outcome
arm group label: Shenfu Injection
arm group type: Experimental
arm group label: 5% Glucose Injection
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Shenfu Injection
description: 80ml Shenfu Injection + 70ml 5% glucose injection, ivdrip, within 30 minutes before PCI and 1 to 5 days (once a day) after PCI (6 times in total). Drug titration time should be no less than 30 minutes.
arm group label: Shenfu Injection
intervention type: Drug
intervention name: 5% Glucose Injection
description: 150 ml 5% glucose injection, ivdrip, within 30 minutes before PCI and 1 to 5 days (once a day) after PCI (6 times in total). Drug titration time should be no less than 30 minutes.
arm group label: 5% Glucose Injection
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Shao-Ping Nie, MD, PhD
phone: 86-10-84005256
email: spnie@ccmu.edu.cn
last name: Xiao Wang, MD
phone: 86-10-84005255
email: spaceeye123@126.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Beijing Anzhen Hospital
investigator full name: Shao-Ping Nie
investigator title: Professor of Medicine, Director, Emergency & Critical Care Center
mesh term: Myocardial Infarction
mesh term: Infarction