<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/NCT03753269</url>
  </required_header>
  <id_info>
    <org_study_id>EARLY-MYO-FASUDIL</org_study_id>
    <nct_id>NCT03753269</nct_id>
  </id_info>
  <brief_title>Early Intracoronary Administration of Fasudil in the Primary PCI of ST-segment-Elevation Myocardial Infarction</brief_title>
  <official_title>Efficacy of Early Intracoronary Administration of Fasudil Hydrochloride on Myocardial Perfusion in the Primary PCI of ST-elevation Myocardial Infarction: an Prospective, Randomized and Multicenter Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>RenJi Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>RenJi Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The study aims to evaluate whether an early intracoronary administration of Fasudil&#xD;
      Hydrochloride during primary PCI of STEMI can improve epicardial and myocardial perfusion as&#xD;
      well as clinical outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Timely reperfusion therapy is the most effective treatment for acute STEMI patients. Primary&#xD;
      PCI has been documented as the best method for restoration of epicardial blood flow.&#xD;
      Nevertheless, recovery of epicardial blood flow does not necessarily equate to a sufficient&#xD;
      reperfusion at myocardial level. Although epicardial TIMI 3 flow could be achieved in the&#xD;
      majority of STEMI patients by contemporary PPCI, it has been well acknowledged that&#xD;
      microvascular obstruction (MVO) is far more prevalent than the epicardial no-reflow&#xD;
      phenomenon and has huge detrimental impact on clinical outcomes.&#xD;
&#xD;
      Routine thrombus aspiration by special catheter during primary PCI has shown negative or even&#xD;
      harmful results in clinical trials. Distal coronary protective devices are also ineffective&#xD;
      to improve myocardial perfusion. On the contrary, peri-procedual administration of several&#xD;
      medications has shown possibilities to reduce MVO. These medications are mostly anti-platelet&#xD;
      agents such as GP IIb/IIIa receptor and microvascular dilators like adenosine, sodium&#xD;
      nitroprusside and verapamil. Theoretically, intracoronary delivery of medications can be more&#xD;
      effective and potentially decrease side effects. Empirical application of aforementioned&#xD;
      agents seems to improve the epicardial flow in patients not achieving TIMI 3 flow after PCI.&#xD;
      However, it is debatable whether early administration of intracoronary medication (meaning&#xD;
      before PCI) may further reduce MVO assuming it could be better to reduce reperfusion injury.&#xD;
      However, this has not been well investigated yet.&#xD;
&#xD;
      Rho-associated protein kinase (Rho kinase) is expressed in many cells, including smooth&#xD;
      muscle cells and vascular endothelial. Activation of Rho kinase leads to increased smooth&#xD;
      muscle intracellular calcium and robust vasoconstriction. Fasudil hydrochloride is a&#xD;
      rho-kinase inhibitor that severs clinically as a potent small vessel dilator, especially in&#xD;
      the field of cerebral circulation. Meanwhile, It has been empirically used in individual&#xD;
      STEMI cases and showed effectiveness in improving coronary flow for PCI therapy. This study&#xD;
      aims to evaluate whether an early intracoronary administration of Fasudil Hydrochloride can&#xD;
      improve myocardial perfusion and clinical outcomes for STEMI patients undergoing primary PCI.&#xD;
      To ensure the complete delivery of agents within coronary, a special-designed targeted&#xD;
      perfusion micro-catheter will be used for drug delivery. Patients in the control arm will be&#xD;
      administrated by intracoronary saline.&#xD;
&#xD;
      For the results, coronary angiography-based index of epical and myocardial perfusion will be&#xD;
      analyzed. MVO will be determined by cardiac magnetic resonance imaging and quantified as the&#xD;
      percentage of left ventricular myocardial mass (% LV). The rate of composite major adverse&#xD;
      cardiac events (MACEs) at 30 days and 6 months since symptom onset will be the clinical&#xD;
      outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 1, 2019</start_date>
  <completion_date type="Anticipated">December 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">June 30, 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>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Complete epicardial and myocardial reperfusion after PCI</measure>
    <time_frame>PCI procedure</time_frame>
    <description>The percentage of patient achieving both thrombolysis in myocardial infarction (TIMI) flow grade (TFG) 3 for epicardial reperfusion and TIMI myocardial perfusion (TMPG) grade 3 for myocardial reperfusion</description>
  </primary_outcome>
  <primary_outcome>
    <measure>CMR-derived microvascular obstruction (MVO)</measure>
    <time_frame>Within one week after the STEMI onset</time_frame>
    <description>MVO is defined as hypoenhanced area within infracted zone presented by CMR gadolinium late enhancement imaging. MVO will be quantified as the percentage of LV mass (% LV)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CMR-derived infarction size</measure>
    <time_frame>Within one week of STEMI onset, repeated on the sixth month</time_frame>
    <description>Infarct size was determined by the extent of late gadolinium enhancement on CMR and expressed as a percentage of LV mass (% LV)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TIMI Flow Grade (TFG)</measure>
    <time_frame>PCI procedure</time_frame>
    <description>Percentage of patients achieving TFG 3</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TIMI Myocardial Perfusion Grade (TMPG)</measure>
    <time_frame>PCI procedure</time_frame>
    <description>Percentage of patients achieving TMPG 3</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TMPFC</measure>
    <time_frame>PCI procedure</time_frame>
    <description>Mean or median value of TMPFC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete ST-segment Resolution</measure>
    <time_frame>90 minutes after PCI procedure</time_frame>
    <description>Percentage of patients achieving ≥ 70% resolution of the initial sum of ST-segment elevation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MACEs</measure>
    <time_frame>30 days and 6 months after STEMI onset</time_frame>
    <description>Incidence of major adverse cardiac events (MACEs) as a composite of all cause death, nonfatal reinfarction, heart failure and stroke after PCI</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">600</enrollment>
  <condition>ST Segment Elevation Myocardial Infarction</condition>
  <arm_group>
    <arm_group_label>Fasudil Hydrochloride</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fasudil Hydrochoride will be delivered into culprit vessel right after the first wire passage</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Same volume of 0.9% saline will be delivered into culprit vessel right after the first wire passage</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fasudil Hydrochloride</intervention_name>
    <description>2.5mg fasudil hydrochloride (diulted to 15ml by 0.9% saline )will be delivered by targeted perfusion micro-catheter into culprit vessel right after the first wire passage</description>
    <arm_group_label>Fasudil Hydrochloride</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo saline</intervention_name>
    <description>15ml 0.9% saline will be delivered by targeted perfusion micro-catheter into culprit vessel right after the first wire passage</description>
    <arm_group_label>Placebo saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: over 18 or 18 years old, less than 75 years old;&#xD;
&#xD;
               -  Patents with myocardial infarction who have symptom onset within 6h before&#xD;
                  randomization;&#xD;
&#xD;
               -  ECG: ≥2 mm ST-segment elevation in 2 contiguous precordial leads or ≥1 mm&#xD;
                  ST-segment elevation in 2 contiguous extremity leads ;&#xD;
&#xD;
               -  Signed informed consent form prior to trial participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. ECG with new left bundle branch block;&#xD;
&#xD;
          2. Contraindications for CMR&#xD;
&#xD;
          3. Repeated STEMI&#xD;
&#xD;
          4. History of cardiovascular diseases&#xD;
&#xD;
               -  PCI within previous 1 month or Previous coronary-artery bypass surgery (CABG)&#xD;
&#xD;
               -  Previously known multi-vessel coronary artery disease not suitable for&#xD;
                  revascularization&#xD;
&#xD;
               -  Hospitalization for cardiac reason within past 48 hours&#xD;
&#xD;
               -  Known acute pericarditis and/or subacute bacterial endocarditis&#xD;
&#xD;
               -  Arterial aneurysm, arterial/venous malformation and aorta dissection;&#xD;
&#xD;
          5. History of other severe diseases&#xD;
&#xD;
               -  Any other diseases with life expectancy ≤12 months&#xD;
&#xD;
               -  • Any history of severe renal or hepatic dysfunction (hepatic failure, cirrhosis,&#xD;
                  portal hypertension and active hepatitis); Neutropenia, thrombocytopenia; Known&#xD;
                  acute pancreatitis&#xD;
&#xD;
          6. Severe cardiac complications&#xD;
&#xD;
               -  Any sign of cardiac rupture&#xD;
&#xD;
               -  Cardiogenic shock (SBP &lt;90 mmHg after fluid infusion or SBP&lt;100 mmHg after&#xD;
                  vasoactive drugs)&#xD;
&#xD;
          7. Not suitable for clinical trial&#xD;
&#xD;
               -  Inclusion in another clinical trial;&#xD;
&#xD;
               -  Previous enrolment in this study or treatment with an investigational drug or&#xD;
                  device under another study protocol in the past 7 days;&#xD;
&#xD;
               -  Pregnancy or lactating;&#xD;
&#xD;
               -  Body weight &lt;40kg or &gt;125kg;&#xD;
&#xD;
               -  Known allergy to any drug that may appear in the study&#xD;
&#xD;
               -  Inability to follow the protocol and comply with follow-up requirements or any&#xD;
                  other reason that the investigator feels would place the patient at increased&#xD;
                  risk.&#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>Jun Pu, Professor</last_name>
    <phone>+86-21-68383164</phone>
    <email>pujun310@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Heng Ge, M.D</last_name>
    <email>dr.geheng@foxmail.com</email>
  </overall_contact_backup>
  <reference>
    <citation>Ding S, Pu J, Qiao ZQ, Shan P, Song W, Du Y, Shen JY, Jin SX, Sun Y, Shen L, Lim YL, He B. TIMI myocardial perfusion frame count: a new method to assess myocardial perfusion and its predictive value for short-term prognosis. Catheter Cardiovasc Interv. 2010 Apr 1;75(5):722-32. doi: 10.1002/ccd.22298.</citation>
    <PMID>19960517</PMID>
  </reference>
  <reference>
    <citation>Gibson CM, Cannon CP, Murphy SA, Ryan KA, Mesley R, Marble SJ, McCabe CH, Van De Werf F, Braunwald E. Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation. 2000 Jan 18;101(2):125-30. doi: 10.1161/01.cir.101.2.125.</citation>
    <PMID>10637197</PMID>
  </reference>
  <reference>
    <citation>Kidambi A, Mather AN, Motwani M, Swoboda P, Uddin A, Greenwood JP, Plein S. The effect of microvascular obstruction and intramyocardial hemorrhage on contractile recovery in reperfused myocardial infarction: insights from cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2013 Jun 27;15(1):58. doi: 10.1186/1532-429X-15-58.</citation>
    <PMID>23806080</PMID>
  </reference>
  <reference>
    <citation>Taniguchi Y, Funayama H, Matsuda J, Fujita K, Nakagawa T, Nakamura T, Umemoto T, Mitsuhashi T, Ako J, Momomura S. Super-selective intracoronary injection of Rho-kinase inhibitor relieves refractory coronary vasospasms: a case report. Int J Cardiol. 2014 Sep;176(1):270-1. doi: 10.1016/j.ijcard.2014.06.096. Epub 2014 Jul 8. No abstract available.</citation>
    <PMID>25065335</PMID>
  </reference>
  <reference>
    <citation>TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. N Engl J Med. 1985 Apr 4;312(14):932-6. doi: 10.1056/NEJM198504043121437. No abstract available.</citation>
    <PMID>4038784</PMID>
  </reference>
  <reference>
    <citation>Masumoto A, Hirooka Y, Shimokawa H, Hironaga K, Setoguchi S, Takeshita A. Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans. Hypertension. 2001 Dec 1;38(6):1307-10. doi: 10.1161/hy1201.096541.</citation>
    <PMID>11751708</PMID>
  </reference>
  <reference>
    <citation>Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T, Tamakawa H, Yamagami K, Inui J, Maekawa M, Narumiya S. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 1997 Oct 30;389(6654):990-4. doi: 10.1038/40187.</citation>
    <PMID>9353125</PMID>
  </reference>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 16, 2018</study_first_submitted>
  <study_first_submitted_qc>November 23, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 26, 2018</study_first_posted>
  <last_update_submitted>November 23, 2018</last_update_submitted>
  <last_update_submitted_qc>November 23, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>myocardial infarction</keyword>
  <keyword>reperfusion therapy</keyword>
  <keyword>microvascular dysfunction</keyword>
  <keyword>Fasudil Hydrochloride</keyword>
  <keyword>myocardial perfusion</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>ST Elevation Myocardial Infarction</mesh_term>
    <mesh_term>Infarction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fasudil</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/NCT03753269
org study id: EARLY-MYO-FASUDIL
nct id: NCT03753269
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The study aims to evaluate whether an early intracoronary administration of Fasudil
      Hydrochloride during primary PCI of STEMI can improve epicardial and myocardial perfusion as
      well as clinical outcomes.
Timely reperfusion therapy is the most effective treatment for acute STEMI patients. Primary
      PCI has been documented as the best method for restoration of epicardial blood flow.
      Nevertheless, recovery of epicardial blood flow does not necessarily equate to a sufficient
      reperfusion at myocardial level. Although epicardial TIMI 3 flow could be achieved in the
      majority of STEMI patients by contemporary PPCI, it has been well acknowledged that
      microvascular obstruction (MVO) is far more prevalent than the epicardial no-reflow
      phenomenon and has huge detrimental impact on clinical outcomes.

      Routine thrombus aspiration by special catheter during primary PCI has shown negative or even
      harmful results in clinical trials. Distal coronary protective devices are also ineffective
      to improve myocardial perfusion. On the contrary, peri-procedual administration of several
      medications has shown possibilities to reduce MVO. These medications are mostly anti-platelet
      agents such as GP IIb/IIIa receptor and microvascular dilators like adenosine, sodium
      nitroprusside and verapamil. Theoretically, intracoronary delivery of medications can be more
      effective and potentially decrease side effects. Empirical application of aforementioned
      agents seems to improve the epicardial flow in patients not achieving TIMI 3 flow after PCI.
      However, it is debatable whether early administration of intracoronary medication (meaning
      before PCI) may further reduce MVO assuming it could be better to reduce reperfusion injury.
      However, this has not been well investigated yet.

      Rho-associated protein kinase (Rho kinase) is expressed in many cells, including smooth
      muscle cells and vascular endothelial. Activation of Rho kinase leads to increased smooth
      muscle intracellular calcium and robust vasoconstriction. Fasudil hydrochloride is a
      rho-kinase inhibitor that severs clinically as a potent small vessel dilator, especially in
      the field of cerebral circulation. Meanwhile, It has been empirically used in individual
      STEMI cases and showed effectiveness in improving coronary flow for PCI therapy. This study
      aims to evaluate whether an early intracoronary administration of Fasudil Hydrochloride can
      improve myocardial perfusion and clinical outcomes for STEMI patients undergoing primary PCI.
      To ensure the complete delivery of agents within coronary, a special-designed targeted
      perfusion micro-catheter will be used for drug delivery. Patients in the control arm will be
      administrated by intracoronary saline.

      For the results, coronary angiography-based index of epical and myocardial perfusion will be
      analyzed. MVO will be determined by cardiac magnetic resonance imaging and quantified as the
      percentage of left ventricular myocardial mass (% LV). The rate of composite major adverse
      cardiac events (MACEs) at 30 days and 6 months since symptom onset will be the clinical
      outcomes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Complete epicardial and myocardial reperfusion after PCI
time frame: PCI procedure
description: The percentage of patient achieving both thrombolysis in myocardial infarction (TIMI) flow grade (TFG) 3 for epicardial reperfusion and TIMI myocardial perfusion (TMPG) grade 3 for myocardial reperfusion
measure: CMR-derived microvascular obstruction (MVO)
time frame: Within one week after the STEMI onset
description: MVO is defined as hypoenhanced area within infracted zone presented by CMR gadolinium late enhancement imaging. MVO will be quantified as the percentage of LV mass (% LV)
measure: CMR-derived infarction size
time frame: Within one week of STEMI onset, repeated on the sixth month
description: Infarct size was determined by the extent of late gadolinium enhancement on CMR and expressed as a percentage of LV mass (% LV)
measure: TIMI Flow Grade (TFG)
time frame: PCI procedure
description: Percentage of patients achieving TFG 3
measure: TIMI Myocardial Perfusion Grade (TMPG)
time frame: PCI procedure
description: Percentage of patients achieving TMPG 3
measure: TMPFC
time frame: PCI procedure
description: Mean or median value of TMPFC
measure: Complete ST-segment Resolution
time frame: 90 minutes after PCI procedure
description: Percentage of patients achieving ≥ 70% resolution of the initial sum of ST-segment elevation
measure: MACEs
time frame: 30 days and 6 months after STEMI onset
description: Incidence of major adverse cardiac events (MACEs) as a composite of all cause death, nonfatal reinfarction, heart failure and stroke after PCI
arm group label: Fasudil Hydrochloride
arm group type: Experimental
description: Fasudil Hydrochoride will be delivered into culprit vessel right after the first wire passage
arm group label: Placebo saline
arm group type: Placebo Comparator
description: Same volume of 0.9% saline will be delivered into culprit vessel right after the first wire passage
intervention type: Drug
intervention name: Fasudil Hydrochloride
description: 2.5mg fasudil hydrochloride (diulted to 15ml by 0.9% saline )will be delivered by targeted perfusion micro-catheter into culprit vessel right after the first wire passage
arm group label: Fasudil Hydrochloride
intervention type: Drug
intervention name: Placebo saline
description: 15ml 0.9% saline will be delivered by targeted perfusion micro-catheter into culprit vessel right after the first wire passage
arm group label: Placebo saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jun Pu, Professor
phone: +86-21-68383164
email: pujun310@hotmail.com
last name: Heng Ge, M.D
email: dr.geheng@foxmail.com
citation: Ding S, Pu J, Qiao ZQ, Shan P, Song W, Du Y, Shen JY, Jin SX, Sun Y, Shen L, Lim YL, He B. TIMI myocardial perfusion frame count: a new method to assess myocardial perfusion and its predictive value for short-term prognosis. Catheter Cardiovasc Interv. 2010 Apr 1;75(5):722-32. doi: 10.1002/ccd.22298.
PMID: 19960517
citation: Gibson CM, Cannon CP, Murphy SA, Ryan KA, Mesley R, Marble SJ, McCabe CH, Van De Werf F, Braunwald E. Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation. 2000 Jan 18;101(2):125-30. doi: 10.1161/01.cir.101.2.125.
PMID: 10637197
citation: Kidambi A, Mather AN, Motwani M, Swoboda P, Uddin A, Greenwood JP, Plein S. The effect of microvascular obstruction and intramyocardial hemorrhage on contractile recovery in reperfused myocardial infarction: insights from cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2013 Jun 27;15(1):58. doi: 10.1186/1532-429X-15-58.
PMID: 23806080
citation: Taniguchi Y, Funayama H, Matsuda J, Fujita K, Nakagawa T, Nakamura T, Umemoto T, Mitsuhashi T, Ako J, Momomura S. Super-selective intracoronary injection of Rho-kinase inhibitor relieves refractory coronary vasospasms: a case report. Int J Cardiol. 2014 Sep;176(1):270-1. doi: 10.1016/j.ijcard.2014.06.096. Epub 2014 Jul 8. No abstract available.
PMID: 25065335
citation: TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. N Engl J Med. 1985 Apr 4;312(14):932-6. doi: 10.1056/NEJM198504043121437. No abstract available.
PMID: 4038784
citation: Masumoto A, Hirooka Y, Shimokawa H, Hironaga K, Setoguchi S, Takeshita A. Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans. Hypertension. 2001 Dec 1;38(6):1307-10. doi: 10.1161/hy1201.096541.
PMID: 11751708
citation: Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T, Tamakawa H, Yamagami K, Inui J, Maekawa M, Narumiya S. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 1997 Oct 30;389(6654):990-4. doi: 10.1038/40187.
PMID: 9353125
responsible party type: Sponsor
mesh term: Myocardial Infarction
mesh term: ST Elevation Myocardial Infarction
mesh term: Infarction
mesh term: Fasudil
sharing ipd: No