<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/NCT02972918</url>
  </required_header>
  <id_info>
    <org_study_id>MML-LEV-2013-01</org_study_id>
    <nct_id>NCT02972918</nct_id>
  </id_info>
  <brief_title>Preoperative levosimendán and Hip Fracture</brief_title>
  <acronym>OPL</acronym>
  <official_title>Preoperative Optimization Levosimendan in Heart Failure Patients Undergoing Hip Fracture</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Universitario de Canarias</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Orion Corporation, Orion Pharma</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital Universitario de Canarias</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate whether preoperative optimization with levosimendan&#xD;
      in heart failure patients undergoing hip fracture surgery improves haemodynamic and tissue&#xD;
      perfusion parameters.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hip fracture is a very predominant entity in elderly patients and it is one of the most&#xD;
      frequent cause of admission in a hospital.&#xD;
&#xD;
      Elderly patients undergoing surgery for hip fracture have a high risk of morbidity and&#xD;
      mortality in the postoperative. Several studies have shown that there is a high risk of&#xD;
      cardiovascular complications in this group of patients and 3-months mortality is 15-20%. One&#xD;
      of the causes of this high morbidity and mortality is the high incidence of chronic cardiac&#xD;
      failure in this patients. The goal of the present study is to evaluate if the optimization of&#xD;
      preoperative cardiac function with levosimendan in patients with left ventricular ejection&#xD;
      fraction &lt; 45% can improve haemodynamic and the tissue perfusion values, and reduce cardiac&#xD;
      morbidity and mortality 3 months postoperatively.&#xD;
&#xD;
      Following written consent, the patients with left ventricular ejection fraction &lt; 45% will be&#xD;
      admitted in the resuscitation and anaesthesia room where they will receive a levosimendan&#xD;
      intravenous injection undergoing a strict haemodynamic vigilance.&#xD;
&#xD;
      Before the levosimendan intravenous injection the patients firs have an echocardiography to&#xD;
      evaluate myocardial function, NT-proBNP. Subsequently, an arterial line is inserted and&#xD;
      optimization achieved by using this arterial line connected to a ProAQT sensor system (&#xD;
      PULSION , Edwards). The system uses pulse wave analysis to assess several parameters&#xD;
      including: stroke volume index (SVI), cardiac index (CI), systemic vascular resistance index&#xD;
      (SVRI), cardiac power index (CPI).The levosimendan will be administered like a continues&#xD;
      injection during 24 hours (0,1 mcg/kg/min) without initial dose. Following the optimization&#xD;
      the patients will be transferred to the operating room in the next 3 days and will come back&#xD;
      to the resuscitation and anaesthesia room where they will stay 24 hours more if there is no&#xD;
      any complication.&#xD;
&#xD;
      All the cardiac complications will be documented and follw-up will be done by after 30 days&#xD;
      and 3 months postoperative.&#xD;
&#xD;
      The patients will be selected for more than 24 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2014</start_date>
  <completion_date type="Actual">April 2019</completion_date>
  <primary_completion_date type="Actual">September 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The effects of Levosimendan on left ventricular function.</measure>
    <time_frame>Baseline and every 24 hours postoperative, 48 h postoperative, and 7 days and after 30 days postoperative.</time_frame>
    <description>Changes of left ventricular function as assessed transthoracic.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in cardiac index</measure>
    <time_frame>48 hours after start of iv infusion</time_frame>
    <description>Measured through arterial pulse wave analysis. A baseline measurement is done before infusion is started</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in transport and tissue perfusion of oxygen</measure>
    <time_frame>1 to 2 day postoperative</time_frame>
    <description>measured by arterial and venous blood gases</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in renal function</measure>
    <time_frame>1 to 7 days postoperative</time_frame>
    <description>Proportion of subjects who develop AKIN stage 1 (increase &gt; 0.3 mg/dl or &gt; 25% in serum creatinine from previous visit)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in NT-proBNP and troponin I</measure>
    <time_frame>24 hours postoperative, 48 h postoperative, 72 h postoperative, and 168 h postoperative</time_frame>
    <description>Plasma NT-proBNP levels were measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse.</measure>
    <time_frame>30 days postoperative</time_frame>
    <description>Development of arrhythmias</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse.</measure>
    <time_frame>30 days postoperative</time_frame>
    <description>Occurence of nausea/vomiting</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse event.</measure>
    <time_frame>30 days postoperative</time_frame>
    <description>Occurence of headache</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of high inotropes (dopamine, Norepinephrine)</measure>
    <time_frame>after 12 hours, after 48 hours and every 24 hours if still in the PO-Unit</time_frame>
    <description>during postoperative unit stay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>morbidity</measure>
    <time_frame>3 months</time_frame>
    <description>All cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major adverse cardiovascular events</measure>
    <time_frame>1st-30th postoperative day</time_frame>
    <description>Perioperative heart failure infarction, stroke</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time on mechanical ventilation</measure>
    <time_frame>1st-30th postoperative day</time_frame>
    <description>Perioperative heart failure infarction, stroke</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>mortality</measure>
    <time_frame>measured at 3 months</time_frame>
    <description>All cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perioperative mortality</measure>
    <time_frame>7 days postoperative</time_frame>
    <description>All cause</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">19</enrollment>
  <condition>Ventricular Dysfunction, Left</condition>
  <condition>Hip Fracture</condition>
  <arm_group>
    <arm_group_label>Levosimendan</arm_group_label>
    <description>At least 12 hours before surgery: Infusion of levosimendan (0,1 mcg/kg/min). 24 hours of infusion without a bolus.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levosimendan</intervention_name>
    <description>24h preoperative infusion of levosimendan (0,1 mcg/Kg/min)</description>
    <arm_group_label>Levosimendan</arm_group_label>
    <other_name>Simdax.</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        All the patients with chronic heart failure of any etiology with hip fracture that present&#xD;
        an acute descompendation of their chronic heart failure and need inotropes because of the&#xD;
        conventional treatment is not enough&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients due to undergo urgent of hip fracture.&#xD;
&#xD;
          2. Patients with cardiac failure (EF &lt; 45 %).&#xD;
&#xD;
          3. Decompensated heart failure.&#xD;
&#xD;
          4. Informed consent provided by the patient.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. &lt;18 years old&#xD;
&#xD;
          2. Emergency surgery&#xD;
&#xD;
          3. Serious aortic stenosis (&lt; 1 cm2)&#xD;
&#xD;
          4. Sustained ventricular tachycardia or atrial fibrillation &gt;140&#xD;
&#xD;
          5. Earlier episodes of &quot;torsades depointes&quot;&#xD;
&#xD;
          6. Systolic blood pressure &lt; 85 mmHg&#xD;
&#xD;
          7. Serious kidney failure (GFR &lt; 30 ml/min)&#xD;
&#xD;
          8. Serious liver failure (known class C Child-Pugh score)&#xD;
&#xD;
          9. Allergy levosimendan&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>María del Carmen Martín Lorenzo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Universitario de Canarias</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Complejo Hospitalario Universitario de Canarias</name>
      <address>
        <city>La Laguna</city>
        <state>S/C Tenerife</state>
        <zip>38320</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <results_reference>
    <citation>Cauley JA, Thompson DE, Ensrud KC, Scott JC, Black D. Risk of mortality following clinical fractures. Osteoporos Int. 2000;11(7):556-61. doi: 10.1007/s001980070075.</citation>
    <PMID>11069188</PMID>
  </results_reference>
  <results_reference>
    <citation>Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet. 1999 Mar 13;353(9156):878-82. doi: 10.1016/S0140-6736(98)09075-8.</citation>
    <PMID>10093980</PMID>
  </results_reference>
  <results_reference>
    <citation>Pedersen SJ, Borgbjerg FM, Schousboe B, Pedersen BD, Jorgensen HL, Duus BR, Lauritzen JB; Hip Fracture Group of Bispebjerg Hospital. A comprehensive hip fracture program reduces complication rates and mortality. J Am Geriatr Soc. 2008 Oct;56(10):1831-8. doi: 10.1111/j.1532-5415.2008.01945.x.</citation>
    <PMID>19054201</PMID>
  </results_reference>
  <results_reference>
    <citation>Ponschab M, Hochmair N, Ghazwinian N, Mueller T, Plochl W. Levosimendan infusion improves haemodynamics in elderly heart failure patients undergoing urgent hip fracture repair. Eur J Anaesthesiol. 2008 Aug;25(8):627-33. doi: 10.1017/S0265021508004080. Epub 2008 Apr 11.</citation>
    <PMID>18405408</PMID>
  </results_reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>November 14, 2016</study_first_submitted>
  <study_first_submitted_qc>November 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 25, 2016</study_first_posted>
  <last_update_submitted>February 3, 2020</last_update_submitted>
  <last_update_submitted_qc>February 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Universitario de Canarias</investigator_affiliation>
    <investigator_full_name>María del Carmen Martín Lorenzo</investigator_full_name>
    <investigator_title>Dr</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ventricular Dysfunction</mesh_term>
    <mesh_term>Ventricular Dysfunction, Left</mesh_term>
    <mesh_term>Fractures, Bone</mesh_term>
    <mesh_term>Hip Fractures</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Simendan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02972918
org study id: MML-LEV-2013-01
nct id: NCT02972918
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to evaluate whether preoperative optimization with levosimendan
      in heart failure patients undergoing hip fracture surgery improves haemodynamic and tissue
      perfusion parameters.
Hip fracture is a very predominant entity in elderly patients and it is one of the most
      frequent cause of admission in a hospital.

      Elderly patients undergoing surgery for hip fracture have a high risk of morbidity and
      mortality in the postoperative. Several studies have shown that there is a high risk of
      cardiovascular complications in this group of patients and 3-months mortality is 15-20%. One
      of the causes of this high morbidity and mortality is the high incidence of chronic cardiac
      failure in this patients. The goal of the present study is to evaluate if the optimization of
      preoperative cardiac function with levosimendan in patients with left ventricular ejection
      fraction < 45% can improve haemodynamic and the tissue perfusion values, and reduce cardiac
      morbidity and mortality 3 months postoperatively.

      Following written consent, the patients with left ventricular ejection fraction < 45% will be
      admitted in the resuscitation and anaesthesia room where they will receive a levosimendan
      intravenous injection undergoing a strict haemodynamic vigilance.

      Before the levosimendan intravenous injection the patients firs have an echocardiography to
      evaluate myocardial function, NT-proBNP. Subsequently, an arterial line is inserted and
      optimization achieved by using this arterial line connected to a ProAQT sensor system (
      PULSION , Edwards). The system uses pulse wave analysis to assess several parameters
      including: stroke volume index (SVI), cardiac index (CI), systemic vascular resistance index
      (SVRI), cardiac power index (CPI).The levosimendan will be administered like a continues
      injection during 24 hours (0,1 mcg/kg/min) without initial dose. Following the optimization
      the patients will be transferred to the operating room in the next 3 days and will come back
      to the resuscitation and anaesthesia room where they will stay 24 hours more if there is no
      any complication.

      All the cardiac complications will be documented and follw-up will be done by after 30 days
      and 3 months postoperative.

      The patients will be selected for more than 24 months.
observational model: Case-Control
time perspective: Prospective
measure: The effects of Levosimendan on left ventricular function.
time frame: Baseline and every 24 hours postoperative, 48 h postoperative, and 7 days and after 30 days postoperative.
description: Changes of left ventricular function as assessed transthoracic.
measure: Change in cardiac index
time frame: 48 hours after start of iv infusion
description: Measured through arterial pulse wave analysis. A baseline measurement is done before infusion is started
measure: Changes in transport and tissue perfusion of oxygen
time frame: 1 to 2 day postoperative
description: measured by arterial and venous blood gases
measure: Changes in renal function
time frame: 1 to 7 days postoperative
description: Proportion of subjects who develop AKIN stage 1 (increase > 0.3 mg/dl or > 25% in serum creatinine from previous visit)
measure: Changes in NT-proBNP and troponin I
time frame: 24 hours postoperative, 48 h postoperative, 72 h postoperative, and 168 h postoperative
description: Plasma NT-proBNP levels were measured
measure: Number of patients with adverse.
time frame: 30 days postoperative
description: Development of arrhythmias
measure: Number of patients with adverse.
time frame: 30 days postoperative
description: Occurence of nausea/vomiting
measure: Number of patients with adverse event.
time frame: 30 days postoperative
description: Occurence of headache
measure: Use of high inotropes (dopamine, Norepinephrine)
time frame: after 12 hours, after 48 hours and every 24 hours if still in the PO-Unit
description: during postoperative unit stay.
measure: morbidity
time frame: 3 months
description: All cause
measure: Major adverse cardiovascular events
time frame: 1st-30th postoperative day
description: Perioperative heart failure infarction, stroke
measure: Time on mechanical ventilation
time frame: 1st-30th postoperative day
description: Perioperative heart failure infarction, stroke
measure: mortality
time frame: measured at 3 months
description: All cause
measure: Perioperative mortality
time frame: 7 days postoperative
description: All cause
arm group label: Levosimendan
description: At least 12 hours before surgery: Infusion of levosimendan (0,1 mcg/kg/min). 24 hours of infusion without a bolus.
intervention type: Drug
intervention name: Levosimendan
description: 24h preoperative infusion of levosimendan (0,1 mcg/Kg/min)
arm group label: Levosimendan
other name: Simdax.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: María del Carmen Martín Lorenzo, MD
role: Principal Investigator
affiliation: Hospital Universitario de Canarias
facility: 
country: Spain
citation: Cauley JA, Thompson DE, Ensrud KC, Scott JC, Black D. Risk of mortality following clinical fractures. Osteoporos Int. 2000;11(7):556-61. doi: 10.1007/s001980070075.
PMID: 11069188
citation: Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet. 1999 Mar 13;353(9156):878-82. doi: 10.1016/S0140-6736(98)09075-8.
PMID: 10093980
citation: Pedersen SJ, Borgbjerg FM, Schousboe B, Pedersen BD, Jorgensen HL, Duus BR, Lauritzen JB; Hip Fracture Group of Bispebjerg Hospital. A comprehensive hip fracture program reduces complication rates and mortality. J Am Geriatr Soc. 2008 Oct;56(10):1831-8. doi: 10.1111/j.1532-5415.2008.01945.x.
PMID: 19054201
citation: Ponschab M, Hochmair N, Ghazwinian N, Mueller T, Plochl W. Levosimendan infusion improves haemodynamics in elderly heart failure patients undergoing urgent hip fracture repair. Eur J Anaesthesiol. 2008 Aug;25(8):627-33. doi: 10.1017/S0265021508004080. Epub 2008 Apr 11.
PMID: 18405408
responsible party type: Principal Investigator
investigator affiliation: Hospital Universitario de Canarias
investigator full name: María del Carmen Martín Lorenzo
investigator title: Dr
mesh term: Ventricular Dysfunction
mesh term: Ventricular Dysfunction, Left
mesh term: Fractures, Bone
mesh term: Hip Fractures
mesh term: Simendan
sharing ipd: Undecided