<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/NCT03000413</url>
  </required_header>
  <id_info>
    <org_study_id>42324015.0.0000.5530</org_study_id>
    <nct_id>NCT03000413</nct_id>
  </id_info>
  <brief_title>Ketamine Efficacy for Acute Severe Bronchospasm in ICU: MACANUDO Trial</brief_title>
  <acronym>MACANUDO</acronym>
  <official_title>Ketamine Efficacy for Acute Severe Bronchospasm in Mechanically Ventilated-critically Ill Patients: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Nossa Senhora da Conceicao</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Nossa Senhora da Conceicao</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Despite few scientific evidence that could support the use of ketamine in adult patients&#xD;
      undergoing acute bronchospasm requiring mechanical ventilation (MV), ketamine is largely&#xD;
      employed in this setting. The aim of this study is therefore assess more definitively the&#xD;
      real benefit of using ketamine in patients with severe bronchospasm, requiring ICU stay and&#xD;
      need for MV in order to establish or refute the use of this drug as &quot;standard therapy&quot; in&#xD;
      these cases.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2015</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Anticipated">January 2017</primary_completion_date>
  <phase>Phase 2/Phase 3</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 (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>bronchospasm improvement</measure>
    <time_frame>3 hours post beginning of drug infusion</time_frame>
    <description>Maximal airway resistance reduction in hour 3-post beginning of drug infusion</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>bronchospasm improvement</measure>
    <time_frame>24 hours post beginning of drug infusion</time_frame>
    <description>Maximal airway resistance reduction in 24th hour post beginning of drug infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to weaning</measure>
    <time_frame>Time (in days) to first spontaneous breathing trial post randomization up to 28 days</time_frame>
    <description>Time (in days) to first spontaneous breathing trial post randomization up to 28 days</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Dynamic complacence improvement</measure>
    <time_frame>3 hours and 24 hours post beginning of drug infusion</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Air trapping improvement</measure>
    <time_frame>3 hours and 24 hours post beginning of drug infusion</time_frame>
    <description>intrinsic PEEP reduction in 3 and 24h post beginning of drug infusion</description>
  </other_outcome>
  <other_outcome>
    <measure>Heart rate</measure>
    <time_frame>3 hours and 24 hours post beginning of drug infusion</time_frame>
    <description>Heart rate in 3 hours and 24h post beginning of drug infusion</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood pressure</measure>
    <time_frame>3 hours and 24 hours post beginning of drug infusion</time_frame>
    <description>Blood pressure variation in 3 hours and 24hours post beginning of drug infusion</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Critical Illness</condition>
  <condition>Asthma</condition>
  <condition>Bronchospasm</condition>
  <arm_group>
    <arm_group_label>Ketamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous ketamine infusion: bolus 2mg per kg and continuous infusion (2mg/kg/h)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fentanyl</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Fentanyl: bolus infusion 1μg per kg and continuous infusion (1μg/kg/h)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>Active treatment</description>
    <arm_group_label>Ketamine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fentanyl</intervention_name>
    <arm_group_label>Fentanyl</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients with acute exacerbation of COPD or status asthmaticus, undergoing controlled&#xD;
             mechanical ventilation&#xD;
&#xD;
          -  acute bronchospasm, defined as airway resistance value (Rsr max) greater than 12, use&#xD;
             of inhaled therapy with bronchodilators and systemic corticosteroids&#xD;
&#xD;
          -  patients requiring the use of continuous intravenous sedation for optimization of&#xD;
             ventilation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  contraindication or history of previous adverse events with the use of the studied&#xD;
             drugs&#xD;
&#xD;
          -  other diagnostic potential Rsr increase of not causing bronchospasm (bronchial&#xD;
             obstruction, acute respiratory distress syndrome adult, pulmonary fibrosis)&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Wagner Nedel, MD, MSc</last_name>
    <phone>+555133572237</phone>
    <email>wagnernedel@uol.com.br</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hospital Nossa Senhora da Conceição</name>
      <address>
        <city>Porto Alegre</city>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wagner Nedel, MD, MSc</last_name>
      <email>wagnernedel@uol.com.br</email>
    </contact>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <reference>
    <citation>Barbas CS, Isola AM, Farias AM, Cavalcanti AB, Gama AM, Duarte AC, Vianna A, Serpa Neto A, Bravim Bde A, Pinheiro Bdo V, Mazza BF, Carvalho CR, Toufen Junior C, David CM, Taniguchi C, Mazza DD, Dragosavac D, Toledo DO, Costa EL, Caser EB, Silva E, Amorim FF, Saddy F, Galas FR, Silva GS, Matos GF, Emmerich JC, Valiatti JL, Teles JM, Victorino JA, Ferreira JC, Prodomo LP, Hajjar LA, Martins LC, Malbouisson LM, Vargas MA, Reis MA, Amato MB, Holanda MA, Park M, Jacomelli M, Tavares M, Damasceno MC, Assuncao MS, Damasceno MP, Youssef NC, Teixeira PJ, Caruso P, Duarte PA, Messeder O, Eid RC, Rodrigues RG, Jesus RF, Kairalla RA, Justino S, Nemer SN, Romero SB, Amado VM. Brazilian recommendations of mechanical ventilation 2013. Part I. Rev Bras Ter Intensiva. 2014 Apr-Jun;26(2):89-121. doi: 10.5935/0103-507x.20140017.</citation>
    <PMID>25028944</PMID>
  </reference>
  <reference>
    <citation>Rowe BH, Sevcik W, Villa-Roel C. Management of severe acute asthma in the emergency department. Curr Opin Crit Care. 2011 Aug;17(4):335-41. doi: 10.1097/MCC.0b013e328348bf09.</citation>
    <PMID>21716106</PMID>
  </reference>
  <reference>
    <citation>Heshmati F, Zeinali MB, Noroozinia H, Abbacivash R, Mahoori A. Use of ketamine in severe status asthmaticus in intensive care unit. Iran J Allergy Asthma Immunol. 2003 Dec;2(4):175-80.</citation>
    <PMID>17301376</PMID>
  </reference>
  <reference>
    <citation>Howton JC, Rose J, Duffy S, Zoltanski T, Levitt MA. Randomized, double-blind, placebo-controlled trial of intravenous ketamine in acute asthma. Ann Emerg Med. 1996 Feb;27(2):170-5. doi: 10.1016/s0196-0644(96)70319-0.</citation>
    <PMID>8629747</PMID>
  </reference>
  <reference>
    <citation>Goyal S, Agrawal A. Ketamine in status asthmaticus: A review. Indian J Crit Care Med. 2013 May;17(3):154-61. doi: 10.4103/0972-5229.117048.</citation>
    <PMID>24082612</PMID>
  </reference>
  <reference>
    <citation>Miller AC, Jamin CT, Elamin EM. Continuous intravenous infusion of ketamine for maintenance sedation. Minerva Anestesiol. 2011 Aug;77(8):812-20.</citation>
    <PMID>21730929</PMID>
  </reference>
  <reference>
    <citation>Abu-Hijleh M, El-Sameed Y, Eldridge K, Vadia E, Chiu H, Dreyfuss Z, Al Rabadi LS. Linear probe endobronchial ultrasound bronchoscopy with guided transbronchial needle aspiration (EBUS-TBNA) in the evaluation of mediastinal and hilar pathology: introducing the procedure to a teaching institution. Lung. 2013 Feb;191(1):109-15. doi: 10.1007/s00408-012-9439-z. Epub 2012 Dec 4.</citation>
    <PMID>23208583</PMID>
  </reference>
  <reference>
    <citation>Allen JY, Macias CG. The efficacy of ketamine in pediatric emergency department patients who present with acute severe asthma. Ann Emerg Med. 2005 Jul;46(1):43-50. doi: 10.1016/j.annemergmed.2005.02.024.</citation>
    <PMID>15988425</PMID>
  </reference>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>December 19, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 22, 2016</study_first_posted>
  <last_update_submitted>December 19, 2016</last_update_submitted>
  <last_update_submitted_qc>December 19, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 22, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Nossa Senhora da Conceicao</investigator_affiliation>
    <investigator_full_name>Wagner Luis Nedel</investigator_full_name>
    <investigator_title>MD, MSc.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchial Spasm</mesh_term>
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
    <mesh_term>Ketamine</mesh_term>
  </intervention_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/NCT03000413
org study id: 42324015.0.0000.5530
nct id: NCT03000413
lead sponsor: 
has dmc: No
Despite few scientific evidence that could support the use of ketamine in adult patients
      undergoing acute bronchospasm requiring mechanical ventilation (MV), ketamine is largely
      employed in this setting. The aim of this study is therefore assess more definitively the
      real benefit of using ketamine in patients with severe bronchospasm, requiring ICU stay and
      need for MV in order to establish or refute the use of this drug as "standard therapy" in
      these cases.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
measure: bronchospasm improvement
time frame: 3 hours post beginning of drug infusion
description: Maximal airway resistance reduction in hour 3-post beginning of drug infusion
measure: bronchospasm improvement
time frame: 24 hours post beginning of drug infusion
description: Maximal airway resistance reduction in 24th hour post beginning of drug infusion
measure: Time to weaning
time frame: Time (in days) to first spontaneous breathing trial post randomization up to 28 days
description: Time (in days) to first spontaneous breathing trial post randomization up to 28 days
measure: Dynamic complacence improvement
time frame: 3 hours and 24 hours post beginning of drug infusion
measure: Air trapping improvement
time frame: 3 hours and 24 hours post beginning of drug infusion
description: intrinsic PEEP reduction in 3 and 24h post beginning of drug infusion
measure: Heart rate
time frame: 3 hours and 24 hours post beginning of drug infusion
description: Heart rate in 3 hours and 24h post beginning of drug infusion
measure: Blood pressure
time frame: 3 hours and 24 hours post beginning of drug infusion
description: Blood pressure variation in 3 hours and 24hours post beginning of drug infusion
arm group label: Ketamine
arm group type: Experimental
description: Intravenous ketamine infusion: bolus 2mg per kg and continuous infusion (2mg/kg/h)
arm group label: Fentanyl
arm group type: Active Comparator
description: Fentanyl: bolus infusion 1μg per kg and continuous infusion (1μg/kg/h)
intervention type: Drug
intervention name: Ketamine
description: Active treatment
arm group label: Ketamine
intervention type: Drug
intervention name: Fentanyl
arm group label: Fentanyl
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Wagner Nedel, MD, MSc
phone: +555133572237
email: wagnernedel@uol.com.br
facility: 
status: Recruiting
contact: 
country: Brazil
citation: Barbas CS, Isola AM, Farias AM, Cavalcanti AB, Gama AM, Duarte AC, Vianna A, Serpa Neto A, Bravim Bde A, Pinheiro Bdo V, Mazza BF, Carvalho CR, Toufen Junior C, David CM, Taniguchi C, Mazza DD, Dragosavac D, Toledo DO, Costa EL, Caser EB, Silva E, Amorim FF, Saddy F, Galas FR, Silva GS, Matos GF, Emmerich JC, Valiatti JL, Teles JM, Victorino JA, Ferreira JC, Prodomo LP, Hajjar LA, Martins LC, Malbouisson LM, Vargas MA, Reis MA, Amato MB, Holanda MA, Park M, Jacomelli M, Tavares M, Damasceno MC, Assuncao MS, Damasceno MP, Youssef NC, Teixeira PJ, Caruso P, Duarte PA, Messeder O, Eid RC, Rodrigues RG, Jesus RF, Kairalla RA, Justino S, Nemer SN, Romero SB, Amado VM. Brazilian recommendations of mechanical ventilation 2013. Part I. Rev Bras Ter Intensiva. 2014 Apr-Jun;26(2):89-121. doi: 10.5935/0103-507x.20140017.
PMID: 25028944
citation: Rowe BH, Sevcik W, Villa-Roel C. Management of severe acute asthma in the emergency department. Curr Opin Crit Care. 2011 Aug;17(4):335-41. doi: 10.1097/MCC.0b013e328348bf09.
PMID: 21716106
citation: Heshmati F, Zeinali MB, Noroozinia H, Abbacivash R, Mahoori A. Use of ketamine in severe status asthmaticus in intensive care unit. Iran J Allergy Asthma Immunol. 2003 Dec;2(4):175-80.
PMID: 17301376
citation: Howton JC, Rose J, Duffy S, Zoltanski T, Levitt MA. Randomized, double-blind, placebo-controlled trial of intravenous ketamine in acute asthma. Ann Emerg Med. 1996 Feb;27(2):170-5. doi: 10.1016/s0196-0644(96)70319-0.
PMID: 8629747
citation: Goyal S, Agrawal A. Ketamine in status asthmaticus: A review. Indian J Crit Care Med. 2013 May;17(3):154-61. doi: 10.4103/0972-5229.117048.
PMID: 24082612
citation: Miller AC, Jamin CT, Elamin EM. Continuous intravenous infusion of ketamine for maintenance sedation. Minerva Anestesiol. 2011 Aug;77(8):812-20.
PMID: 21730929
citation: Abu-Hijleh M, El-Sameed Y, Eldridge K, Vadia E, Chiu H, Dreyfuss Z, Al Rabadi LS. Linear probe endobronchial ultrasound bronchoscopy with guided transbronchial needle aspiration (EBUS-TBNA) in the evaluation of mediastinal and hilar pathology: introducing the procedure to a teaching institution. Lung. 2013 Feb;191(1):109-15. doi: 10.1007/s00408-012-9439-z. Epub 2012 Dec 4.
PMID: 23208583
citation: Allen JY, Macias CG. The efficacy of ketamine in pediatric emergency department patients who present with acute severe asthma. Ann Emerg Med. 2005 Jul;46(1):43-50. doi: 10.1016/j.annemergmed.2005.02.024.
PMID: 15988425
responsible party type: Principal Investigator
investigator affiliation: Hospital Nossa Senhora da Conceicao
investigator full name: Wagner Luis Nedel
investigator title: MD, MSc.
mesh term: Bronchial Spasm
mesh term: Critical Illness
mesh term: Fentanyl
mesh term: Ketamine