<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/NCT03303378</url>
  </required_header>
  <id_info>
    <org_study_id>MelonRI</org_study_id>
    <nct_id>NCT03303378</nct_id>
  </id_info>
  <brief_title>Effects of Melatonin on Reperfusion Injury</brief_title>
  <official_title>Effects of Melatonin on Reperfusion Injury in Patients With ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese PLA General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chinese PLA General 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>
      Acute myocardial infarction is a major cause of mortality and morbidity. Primary percutaneous&#xD;
      coronary intervention (pPCI) is currently the most effective treatment strategy in acute&#xD;
      myocardial infarction. However, a sizable number of patients fail to restore optimal&#xD;
      myocardial reperfusion, mostly because of the 'no-reflow' phenomenon. Melatonin is the chief&#xD;
      indoleamine produced by the pineal gland, and a well-known antioxidant and free radical&#xD;
      scavenger. Several studies have shown that melatonin protects against ischemia/reperfusion&#xD;
      injury (IRI). In our previous study, melatonin markedly reduced infarcted area, improved&#xD;
      cardiac function and reduced lactate dehydrogenase release in rats. The investigators planned&#xD;
      to research the cardioprotective effects of intravenous melatonin administered prior to&#xD;
      reperfusion and continued after restoration of coronary blood flow in patients with ST&#xD;
      segment elevation myocardial infarction undergoing pPCI.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">November 1, 2017</start_date>
  <completion_date type="Anticipated">November 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2019</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>Patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The salvage index</measure>
    <time_frame>3 months after primary percutaneous coronary intervention</time_frame>
    <description>The salvage index measured by cardiac magnetic resonance</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The final infarct size</measure>
    <time_frame>3 months after primary percutaneous coronary intervention</time_frame>
    <description>The final infarct size measured by cardiac magnetic resonance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>major adverse cardiovascular events (MACE)</measure>
    <time_frame>3 months after primary percutaneous coronary intervention</time_frame>
    <description>recurrent myocardial infarction, recurrent angina, revascularization, heart failure, cardiac death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>treatment-emergent adverse events (TEAEs)</measure>
    <time_frame>3 months after primary percutaneous coronary intervention</time_frame>
    <description>hypoglycemia, nausea</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">190</enrollment>
  <condition>Reperfusion Injury, Myocardial</condition>
  <arm_group>
    <arm_group_label>Melatonin group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive a total intravenous melatonin dose of 11.61 mg (aproximately 166 μg/kg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients will receive the same dose of placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>melatonin (Helsinn Chemical Co, Biasca, Switzerland)</intervention_name>
    <description>Patients will receive a total intravenous melatonin (Helsinn Chemical Co, Biasca, Switzerland) dose of 11.61 mg (aproximately 166 μg/kg). The dose will be distributed in a volume of 500 ml of an isotonic and sterile solution of 100 μM melatonin during 150 min with a drip rate of 4.2 ml/min.&#xD;
The temporal distribution of perfusion will be: 30 min previous to percutaneous revascularization and remainder doses in a subsequent 120 min (1 h during the angioplasty +60 min post-intervention).</description>
    <arm_group_label>Melatonin group</arm_group_label>
    <other_name>melatonin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>The temporal distribution of perfusion will be: 30 min previous to percutaneous revascularization and remainder doses in a subsequent 120 min (1 h during the angioplasty +60 min post-intervention).</description>
    <arm_group_label>Control group</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        ST segment elevation myocardial infarction undergoing primary percutaneous poronary&#xD;
        intervention&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  unconscious at presentation&#xD;
&#xD;
          -  had cardiogenic shock&#xD;
&#xD;
          -  had a history of myocardial infarction&#xD;
&#xD;
          -  stent thrombosis&#xD;
&#xD;
          -  renal insufficiency&#xD;
&#xD;
          -  had previously undergone coronary artery bypass surgery&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>wei ren chen, M.D.</last_name>
    <phone>+8610-66876231</phone>
    <email>chen_weiren@sina.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>PLA General Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100853</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wei Ren Chen, M.D.</last_name>
      <phone>+8610-66939709</phone>
      <email>chen_weiren@sina.com</email>
    </contact>
    <investigator>
      <last_name>Yun Dai Chen, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <results_reference>
    <citation>Dominguez-Rodriguez A, Abreu-Gonzalez P, de la Torre-Hernandez JM, Consuegra-Sanchez L, Piccolo R, Gonzalez-Gonzalez J, Garcia-Camarero T, Del Mar Garcia-Saiz M, Aldea-Perona A, Reiter RJ; MARIA Investigators. Usefulness of Early Treatment With Melatonin to Reduce Infarct Size in Patients With ST-Segment Elevation Myocardial Infarction Receiving Percutaneous Coronary Intervention (From the Melatonin Adjunct in the Acute Myocardial Infarction Treated With Angioplasty Trial). Am J Cardiol. 2017 Aug 15;120(4):522-526. doi: 10.1016/j.amjcard.2017.05.018. Epub 2017 May 30.</citation>
    <PMID>28645475</PMID>
  </results_reference>
  <results_reference>
    <citation>Zhou H, Zhang Y, Hu S, Shi C, Zhu P, Ma Q, Jin Q, Cao F, Tian F, Chen Y. Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis. J Pineal Res. 2017 Aug;63(1):e12413. doi: 10.1111/jpi.12413. Epub 2017 Apr 27.</citation>
    <PMID>28398674</PMID>
  </results_reference>
  <results_reference>
    <citation>Dominguez-Rodriguez A, Abreu-Gonzalez P, Garcia-Gonzalez MJ, Kaski JC, Reiter RJ, Jimenez-Sosa A. A unicenter, randomized, double-blind, parallel-group, placebo-controlled study of Melatonin as an Adjunct in patients with acute myocaRdial Infarction undergoing primary Angioplasty The Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty (MARIA) trial: study design and rationale. Contemp Clin Trials. 2007 Jul;28(4):532-9. doi: 10.1016/j.cct.2006.10.007. Epub 2006 Oct 17.</citation>
    <PMID>17123867</PMID>
  </results_reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>October 2, 2017</study_first_submitted>
  <study_first_submitted_qc>October 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 6, 2017</study_first_posted>
  <last_update_submitted>October 4, 2017</last_update_submitted>
  <last_update_submitted_qc>October 4, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chinese PLA General Hospital</investigator_affiliation>
    <investigator_full_name>Chen Wei Ren, MD</investigator_full_name>
    <investigator_title>doctor</investigator_title>
  </responsible_party>
  <keyword>melatonin</keyword>
  <keyword>Reperfusion Injury</keyword>
  <keyword>myocardial infarction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Reperfusion Injury</mesh_term>
    <mesh_term>Myocardial Reperfusion Injury</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melatonin</mesh_term>
  </intervention_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/NCT03303378
org study id: MelonRI
nct id: NCT03303378
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Acute myocardial infarction is a major cause of mortality and morbidity. Primary percutaneous
      coronary intervention (pPCI) is currently the most effective treatment strategy in acute
      myocardial infarction. However, a sizable number of patients fail to restore optimal
      myocardial reperfusion, mostly because of the 'no-reflow' phenomenon. Melatonin is the chief
      indoleamine produced by the pineal gland, and a well-known antioxidant and free radical
      scavenger. Several studies have shown that melatonin protects against ischemia/reperfusion
      injury (IRI). In our previous study, melatonin markedly reduced infarcted area, improved
      cardiac function and reduced lactate dehydrogenase release in rats. The investigators planned
      to research the cardioprotective effects of intravenous melatonin administered prior to
      reperfusion and continued after restoration of coronary blood flow in patients with ST
      segment elevation myocardial infarction undergoing pPCI.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: The salvage index
time frame: 3 months after primary percutaneous coronary intervention
description: The salvage index measured by cardiac magnetic resonance
measure: The final infarct size
time frame: 3 months after primary percutaneous coronary intervention
description: The final infarct size measured by cardiac magnetic resonance
measure: major adverse cardiovascular events (MACE)
time frame: 3 months after primary percutaneous coronary intervention
description: recurrent myocardial infarction, recurrent angina, revascularization, heart failure, cardiac death.
measure: treatment-emergent adverse events (TEAEs)
time frame: 3 months after primary percutaneous coronary intervention
description: hypoglycemia, nausea
arm group label: Melatonin group
arm group type: Experimental
description: Patients will receive a total intravenous melatonin dose of 11.61 mg (aproximately 166 μg/kg).
arm group label: Control group
arm group type: Placebo Comparator
description: Patients will receive the same dose of placebo.
intervention type: Drug
intervention name: melatonin (Helsinn Chemical Co, Biasca, Switzerland)
description: Patients will receive a total intravenous melatonin (Helsinn Chemical Co, Biasca, Switzerland) dose of 11.61 mg (aproximately 166 μg/kg). The dose will be distributed in a volume of 500 ml of an isotonic and sterile solution of 100 μM melatonin during 150 min with a drip rate of 4.2 ml/min.
The temporal distribution of perfusion will be: 30 min previous to percutaneous revascularization and remainder doses in a subsequent 120 min (1 h during the angioplasty +60 min post-intervention).
arm group label: Melatonin group
other name: melatonin
intervention type: Drug
intervention name: Placebos
description: The temporal distribution of perfusion will be: 30 min previous to percutaneous revascularization and remainder doses in a subsequent 120 min (1 h during the angioplasty +60 min post-intervention).
arm group label: Control group
other name: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: wei ren chen, M.D.
phone: +8610-66876231
email: chen_weiren@sina.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
citation: Dominguez-Rodriguez A, Abreu-Gonzalez P, de la Torre-Hernandez JM, Consuegra-Sanchez L, Piccolo R, Gonzalez-Gonzalez J, Garcia-Camarero T, Del Mar Garcia-Saiz M, Aldea-Perona A, Reiter RJ; MARIA Investigators. Usefulness of Early Treatment With Melatonin to Reduce Infarct Size in Patients With ST-Segment Elevation Myocardial Infarction Receiving Percutaneous Coronary Intervention (From the Melatonin Adjunct in the Acute Myocardial Infarction Treated With Angioplasty Trial). Am J Cardiol. 2017 Aug 15;120(4):522-526. doi: 10.1016/j.amjcard.2017.05.018. Epub 2017 May 30.
PMID: 28645475
citation: Zhou H, Zhang Y, Hu S, Shi C, Zhu P, Ma Q, Jin Q, Cao F, Tian F, Chen Y. Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis. J Pineal Res. 2017 Aug;63(1):e12413. doi: 10.1111/jpi.12413. Epub 2017 Apr 27.
PMID: 28398674
citation: Dominguez-Rodriguez A, Abreu-Gonzalez P, Garcia-Gonzalez MJ, Kaski JC, Reiter RJ, Jimenez-Sosa A. A unicenter, randomized, double-blind, parallel-group, placebo-controlled study of Melatonin as an Adjunct in patients with acute myocaRdial Infarction undergoing primary Angioplasty The Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty (MARIA) trial: study design and rationale. Contemp Clin Trials. 2007 Jul;28(4):532-9. doi: 10.1016/j.cct.2006.10.007. Epub 2006 Oct 17.
PMID: 17123867
responsible party type: Principal Investigator
investigator affiliation: Chinese PLA General Hospital
investigator full name: Chen Wei Ren, MD
investigator title: doctor
mesh term: Reperfusion Injury
mesh term: Myocardial Reperfusion Injury
mesh term: Wounds and Injuries
mesh term: Melatonin
sharing ipd: No