<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/NCT04500899</url>
  </required_header>
  <id_info>
    <org_study_id>2020-11414</org_study_id>
    <nct_id>NCT04500899</nct_id>
  </id_info>
  <brief_title>Use of Phenylephrine for Assessment of Mitral Regurgitation Severity</brief_title>
  <official_title>Evaluating the Severity of Mitral Regurgitation Using Phenylephrine During Transesophageal Echocardiography</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Montefiore Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Montefiore Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study proposes to develop a phenylephrine protocol to be used during transesophageal&#xD;
      echocardiography, whereby intravenous phenylephrine would be used to increase afterload with&#xD;
      the intent to mimic the awake hemodynamic profile and variation that occurs with normal&#xD;
      physical activity. The expectation is to see changes in severity of Mitral Regurgitation (MR)&#xD;
      grade with increasing afterload, which in turn can provide more accurate quantification of MR&#xD;
      severity to assist in clinical decision making.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Routine echocardiography which is used to assess the severity of mitral regurgitation,&#xD;
      sometimes underestimates the severity of mitral regurgitation, due to hemodynamic variations&#xD;
      that occurs with normal physical activity and under the effect of sedation which is used to&#xD;
      perform transesophageal echocardiography. By using phenylephrine during transesophageal&#xD;
      echocardiography, the study intends to offset the hemodynamic variation that occurs with&#xD;
      sedation and better assess the severity of mitral regurgitation, which would further assist&#xD;
      in clinical decision-making regarding treatment. The goal of this study is to compare the&#xD;
      severity of mitral regurgitation grade before and after the administration of phenylephrine&#xD;
      during transesophageal echocardiography and to demonstrate a 25% increase in severity of&#xD;
      mitral regurgitation grade compared to the baseline conditions, following the administration&#xD;
      of phenylephrine.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 1, 2020</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">June 2024</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The percentage of patients with greater than 25% increase in MR regurgitant volume (Rvol) after the use of phenylephrine during transesophageal echocardiography.</measure>
    <time_frame>Before and after phenylephrine administration during transesophageal echocardiography, approximately 40 minutes</time_frame>
    <description>The purpose of this study is to compare the echocardiographic parameters of MR grade before and after the use of phenylephrine during transesophageal echocardiography (TEE) and to document an increase in echocardiographic parameters of MR grade after the use of phenylephrine.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">35</enrollment>
  <condition>Mitral Regurgitation</condition>
  <arm_group>
    <arm_group_label>Mydfrin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phenylephrine is available as phenylephrine hydrochloride injection, 10 mg/mL in 1 mL vial. For intravascular bolus administration, the investigators will prepare a solution containing 100 mcg/mL of phenylephrine hydrochloride, by withdrawing 10 mg (1ml of 10mg/mL) of phenylephrine injection and diluting with 99 mL of 5% dextrose injection or 0.9% sodium chloride injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mydfrin</intervention_name>
    <description>A test dose of 20 mcg of Mydfrin will be administered through the peripheral intravenous line. Subsequent Mydfrin injections will then be administered in 40 mcg aliquots every 10-15 minutes, until the mean arterial blood pressure (MAP) increases by ≥ 20 mm Hg from the baseline MAP, however making sure not to exceed a MAP of 100 mmHg. Once a desired blood pressure has been achieved and maintained, echocardiographic evaluation of mitral regurgitation would be performed.</description>
    <arm_group_label>Mydfrin</arm_group_label>
    <other_name>Phenylephrine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients 18 years or older with MR on baseline echocardiographic evaluation who are&#xD;
             scheduled to undergo TEE for further evaluation of mitral regurgitation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The following patients will be excluded from the study:&#xD;
&#xD;
               1. Patients who are not clinically eligible for TEE.&#xD;
&#xD;
               2. Patients with contraindications to esophageal intubation.&#xD;
&#xD;
               3. Patients with hemodynamic instability.&#xD;
&#xD;
               4. Patients with acute decompensated heart failure (HF).&#xD;
&#xD;
               5. Patients with un-revascularized severe coronary artery disease (triple vessel or&#xD;
                  left main disease).&#xD;
&#xD;
               6. Patients with ongoing unstable angina or ongoing myocardial infarction (MI)&#xD;
&#xD;
               7. Patients with significant arrhythmias including atrial fibrillation.&#xD;
&#xD;
               8. Patients with uncontrolled hypertension (BP ≥ 150/90 mmHg).&#xD;
&#xD;
               9. Patients with preexisting bradycardia (HR &lt; 50) and heart blocks.&#xD;
&#xD;
              10. Patients with severe symptomatic peripheral vascular disease.&#xD;
&#xD;
              11. Patients with severe pulmonary hypertension (estimated systolic pulmonary&#xD;
                  arterial pressure sPAP ≥ 60mm Hg).&#xD;
&#xD;
              12. Patients who are at high risk for intracranial bleeding such as patients with&#xD;
                  previous strokes, transient ischemic attack (TIA) and vascular malformations.&#xD;
&#xD;
              13. Additionally, patients with mean arterial blood pressure MAP &gt; 100 mmHg during&#xD;
                  TEE and those with severe MR, effective regurgitant orifice area (ERO &gt; 39cm2) on&#xD;
                  baseline TEE evaluation will not be given phenylephrine and excluded from the&#xD;
                  study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mario Garcia, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Montefiore Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Safeera Javed, MD</last_name>
    <phone>929-293-6103</phone>
    <email>safeerajaved@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Waqas Hanif, MD</last_name>
    <phone>646-270-1421</phone>
    <email>whanif@montefiore.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10470</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mario Garcia, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Carabello BA. The current therapy for mitral regurgitation. J Am Coll Cardiol. 2008 Jul 29;52(5):319-26. doi: 10.1016/j.jacc.2008.02.084.</citation>
    <PMID>18652937</PMID>
  </reference>
  <reference>
    <citation>Lehmann KG, Francis CK, Dodge HT. Mitral regurgitation in early myocardial infarction. Incidence, clinical detection, and prognostic implications. TIMI Study Group. Ann Intern Med. 1992 Jul 1;117(1):10-7. doi: 10.7326/0003-4819-117-1-10. Erratum In: Ann Intern Med 1992 Aug 15;117(4):349.</citation>
    <PMID>1596042</PMID>
  </reference>
  <reference>
    <citation>Singh JP, Evans JC, Levy D, Larson MG, Freed LA, Fuller DL, Lehman B, Benjamin EJ. Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation (the Framingham Heart Study). Am J Cardiol. 1999 Mar 15;83(6):897-902. doi: 10.1016/s0002-9149(98)01064-9. Erratum In: Am J Cardiol 1999 Nov 1;84(9):1143.</citation>
    <PMID>10190406</PMID>
  </reference>
  <reference>
    <citation>Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Fleisher LA, Jneid H, Mack MJ, McLeod CJ, O'Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A. 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017 Jul 11;70(2):252-289. doi: 10.1016/j.jacc.2017.03.011. Epub 2017 Mar 15. No abstract available.</citation>
    <PMID>28315732</PMID>
  </reference>
  <reference>
    <citation>Shiran A, Merdler A, Ismir E, Ammar R, Zlotnick AY, Aravot D, Lazarovici H, Zisman E, Pizov R, Lewis BS. Intraoperative transesophageal echocardiography using a quantitative dynamic loading test for the evaluation of ischemic mitral regurgitation. J Am Soc Echocardiogr. 2007 Jun;20(6):690-7. doi: 10.1016/j.echo.2006.11.004.</citation>
    <PMID>17543738</PMID>
  </reference>
  <reference>
    <citation>Sanfilippo F, Johnson C, Bellavia D, Morsolini M, Romano G, Santonocito C, Centineo L, Pastore F, Pilato M, Arcadipane A. Mitral Regurgitation Grading in the Operating Room: A Systematic Review and Meta-analysis Comparing Preoperative and Intraoperative Assessments During Cardiac Surgery. J Cardiothorac Vasc Anesth. 2017 Oct;31(5):1681-1691. doi: 10.1053/j.jvca.2017.02.046. Epub 2017 Feb 13.</citation>
    <PMID>28506541</PMID>
  </reference>
  <reference>
    <citation>Kolev N, Brase R, Wolner E, Zimpfer M. Quantification of mitral regurgitant flow using proximal isovelocity surface area method: a transesophageal echocardiography perioperative study. J Cardiothorac Vasc Anesth. 1998 Feb;12(1):22-6. doi: 10.1016/s1053-0770(98)90050-7.</citation>
    <PMID>9509352</PMID>
  </reference>
  <reference>
    <citation>Recusani F, Bargiggia GS, Yoganathan AP, Raisaro A, Valdes-Cruz LM, Sung HW, Bertucci C, Gallati M, Moises VA, Simpson IA, et al. A new method for quantification of regurgitant flow rate using color Doppler flow imaging of the flow convergence region proximal to a discrete orifice. An in vitro study. Circulation. 1991 Feb;83(2):594-604. doi: 10.1161/01.cir.83.2.594.</citation>
    <PMID>1991377</PMID>
  </reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 23, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>July 18, 2023</last_update_submitted>
  <last_update_submitted_qc>July 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mitral Valve Insufficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Phenylephrine</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/NCT04500899
org study id: 2020-11414
nct id: NCT04500899
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The study proposes to develop a phenylephrine protocol to be used during transesophageal
      echocardiography, whereby intravenous phenylephrine would be used to increase afterload with
      the intent to mimic the awake hemodynamic profile and variation that occurs with normal
      physical activity. The expectation is to see changes in severity of Mitral Regurgitation (MR)
      grade with increasing afterload, which in turn can provide more accurate quantification of MR
      severity to assist in clinical decision making.
Routine echocardiography which is used to assess the severity of mitral regurgitation,
      sometimes underestimates the severity of mitral regurgitation, due to hemodynamic variations
      that occurs with normal physical activity and under the effect of sedation which is used to
      perform transesophageal echocardiography. By using phenylephrine during transesophageal
      echocardiography, the study intends to offset the hemodynamic variation that occurs with
      sedation and better assess the severity of mitral regurgitation, which would further assist
      in clinical decision-making regarding treatment. The goal of this study is to compare the
      severity of mitral regurgitation grade before and after the administration of phenylephrine
      during transesophageal echocardiography and to demonstrate a 25% increase in severity of
      mitral regurgitation grade compared to the baseline conditions, following the administration
      of phenylephrine.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: The percentage of patients with greater than 25% increase in MR regurgitant volume (Rvol) after the use of phenylephrine during transesophageal echocardiography.
time frame: Before and after phenylephrine administration during transesophageal echocardiography, approximately 40 minutes
description: The purpose of this study is to compare the echocardiographic parameters of MR grade before and after the use of phenylephrine during transesophageal echocardiography (TEE) and to document an increase in echocardiographic parameters of MR grade after the use of phenylephrine.
arm group label: Mydfrin
arm group type: Experimental
description: Phenylephrine is available as phenylephrine hydrochloride injection, 10 mg/mL in 1 mL vial. For intravascular bolus administration, the investigators will prepare a solution containing 100 mcg/mL of phenylephrine hydrochloride, by withdrawing 10 mg (1ml of 10mg/mL) of phenylephrine injection and diluting with 99 mL of 5% dextrose injection or 0.9% sodium chloride injection.
intervention type: Drug
intervention name: Mydfrin
description: A test dose of 20 mcg of Mydfrin will be administered through the peripheral intravenous line. Subsequent Mydfrin injections will then be administered in 40 mcg aliquots every 10-15 minutes, until the mean arterial blood pressure (MAP) increases by ≥ 20 mm Hg from the baseline MAP, however making sure not to exceed a MAP of 100 mmHg. Once a desired blood pressure has been achieved and maintained, echocardiographic evaluation of mitral regurgitation would be performed.
arm group label: Mydfrin
other name: Phenylephrine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mario Garcia, MD
role: Principal Investigator
affiliation: Montefiore Medical Center
last name: Safeera Javed, MD
phone: 929-293-6103
email: safeerajaved@gmail.com
last name: Waqas Hanif, MD
phone: 646-270-1421
email: whanif@montefiore.org
facility: 
status: Recruiting
contact: 
country: United States
citation: Carabello BA. The current therapy for mitral regurgitation. J Am Coll Cardiol. 2008 Jul 29;52(5):319-26. doi: 10.1016/j.jacc.2008.02.084.
PMID: 18652937
citation: Lehmann KG, Francis CK, Dodge HT. Mitral regurgitation in early myocardial infarction. Incidence, clinical detection, and prognostic implications. TIMI Study Group. Ann Intern Med. 1992 Jul 1;117(1):10-7. doi: 10.7326/0003-4819-117-1-10. Erratum In: Ann Intern Med 1992 Aug 15;117(4):349.
PMID: 1596042
citation: Singh JP, Evans JC, Levy D, Larson MG, Freed LA, Fuller DL, Lehman B, Benjamin EJ. Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation (the Framingham Heart Study). Am J Cardiol. 1999 Mar 15;83(6):897-902. doi: 10.1016/s0002-9149(98)01064-9. Erratum In: Am J Cardiol 1999 Nov 1;84(9):1143.
PMID: 10190406
citation: Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Fleisher LA, Jneid H, Mack MJ, McLeod CJ, O'Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A. 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017 Jul 11;70(2):252-289. doi: 10.1016/j.jacc.2017.03.011. Epub 2017 Mar 15. No abstract available.
PMID: 28315732
citation: Shiran A, Merdler A, Ismir E, Ammar R, Zlotnick AY, Aravot D, Lazarovici H, Zisman E, Pizov R, Lewis BS. Intraoperative transesophageal echocardiography using a quantitative dynamic loading test for the evaluation of ischemic mitral regurgitation. J Am Soc Echocardiogr. 2007 Jun;20(6):690-7. doi: 10.1016/j.echo.2006.11.004.
PMID: 17543738
citation: Sanfilippo F, Johnson C, Bellavia D, Morsolini M, Romano G, Santonocito C, Centineo L, Pastore F, Pilato M, Arcadipane A. Mitral Regurgitation Grading in the Operating Room: A Systematic Review and Meta-analysis Comparing Preoperative and Intraoperative Assessments During Cardiac Surgery. J Cardiothorac Vasc Anesth. 2017 Oct;31(5):1681-1691. doi: 10.1053/j.jvca.2017.02.046. Epub 2017 Feb 13.
PMID: 28506541
citation: Kolev N, Brase R, Wolner E, Zimpfer M. Quantification of mitral regurgitant flow using proximal isovelocity surface area method: a transesophageal echocardiography perioperative study. J Cardiothorac Vasc Anesth. 1998 Feb;12(1):22-6. doi: 10.1016/s1053-0770(98)90050-7.
PMID: 9509352
citation: Recusani F, Bargiggia GS, Yoganathan AP, Raisaro A, Valdes-Cruz LM, Sung HW, Bertucci C, Gallati M, Moises VA, Simpson IA, et al. A new method for quantification of regurgitant flow rate using color Doppler flow imaging of the flow convergence region proximal to a discrete orifice. An in vitro study. Circulation. 1991 Feb;83(2):594-604. doi: 10.1161/01.cir.83.2.594.
PMID: 1991377
responsible party type: Sponsor
mesh term: Mitral Valve Insufficiency
mesh term: Phenylephrine
sharing ipd: No