<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/NCT04497831</url>
  </required_header>
  <id_info>
    <org_study_id>NKBBN/433/2018</org_study_id>
    <secondary_id>2019-000662-37</secondary_id>
    <nct_id>NCT04497831</nct_id>
  </id_info>
  <brief_title>Morphine for Dyspnea in Pulmonary Fibrosis</brief_title>
  <official_title>Determining the Effectiveness of Nebulized Morphine in Treating Dyspnea in Advanced Idiopathic Pulmonary Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Gdansk</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Gdansk</source>
  <oversight_info>
    <has_dmc>No</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>
      &quot;Determination of the effectiveness of nebulized morphine in the treatment of dyspnea in&#xD;
      patients with advanced idiopathic pulmonary fibrosis&quot;&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">September 21, 2020</start_date>
  <completion_date type="Anticipated">September 21, 2022</completion_date>
  <primary_completion_date type="Anticipated">September 21, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>The study is a randomized, double-blind, placebo-controlled analysis conducted with crossover arms. The study consists of two treatment periods lasting a total of 5 days: 2 days of nebulization with 0.9% NaCl and 2 days of nebulization with 2.0% morphine hydrochloride solution separated by 1 day intended for elimination of the drug from the body (wash-out). The order of treatment periods (morphine -&gt; placebo, placebo -&gt; morphine) will be randomized for each patient by a hospital pharmacist using online software: Research Randomizer 4.0. The draw will assign the participant to one of two sequences:&#xD;
A. 2 days - 0.9% NaCl; 1 day - wash-out; 2 days - morphine hydrochloride. B. 2 days - morphine hydrochloride; 1 day - wash-out; 2 days - 0.9% NaCl</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The primary end point is a reduction of breathlessness intensity by ≥20 mm at 100 mm visual analogue scale (VAS) after nebulization, during daily, normal activities</measure>
    <time_frame>Breathlessness during daily, normal activities will be measured with VAS 1 hour before nebulization and 4 hours after</time_frame>
    <description>The primary end point is a reduction of breathlessness intensity by ≥20 mm at 100 mm visual analogue scale (VAS) after nebulization, during daily, normal activities</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary end point</measure>
    <time_frame>Cough and chest pain severity during normal activities will be assessed with VAS 1h before nebulization and 4 hours after Six minute walking test, along with breathlessness, cough and chest pain assessment in VAS, will be performed 1h before nebuli</time_frame>
    <description>Secondary end points are:&#xD;
reduction of breathlessness intensity by ≥20 mm at 100 mm visual analogue scale (VAS) following six minute walking test (6MWT) performed after nebulization&#xD;
improvement of 6MWT distance by ≥30 m&#xD;
reduction of cough severity by ≥17 mm at 100 mm visual analogue scale (VAS) after nebulization, during normal activities&#xD;
reduction of chest pain severity by ≥19 mm at 100 mm visual analogue scale (VAS) after nebulization, during normal activities&#xD;
reduction of cough severity by ≥17 mm at 100 mm visual analogue scale (VAS) during six minute walking test (6MWT) performed after nebulization&#xD;
reduction of chest pain severity by ≥19 mm at 100 mm visual analogue scale (VAS) following six minute walking test (6MWT) performed after nebulization</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Idiopathic Pulmonary Fibrosis (IPF)</condition>
  <arm_group>
    <arm_group_label>Study Drug</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Morphine hydrochloride</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine hydrochloride</intervention_name>
    <description>5 mg milligram(s) per day per two days of dosage</description>
    <arm_group_label>Study Drug</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Inhalation use</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  IPF diagnosis in accordance with guidelines&#xD;
&#xD;
               -  Period of stable disease&#xD;
&#xD;
               -  Dyspnea rated 3 to 4 in mMRC scale&#xD;
&#xD;
               -  Current non-smoker&#xD;
&#xD;
               -  Other potential causes of breathlessness such as kidney or heart failure&#xD;
                  optimally treated in the opinion of the principal investigator&#xD;
&#xD;
               -  Able to complete questionnaires and trial assessments&#xD;
&#xD;
               -  Ability to give informed consent&#xD;
&#xD;
               -  If female, must be:&#xD;
&#xD;
                    1. postmenopausal (no menses for 12 months without an alternative medical&#xD;
                       cause)&#xD;
&#xD;
                    2. sterile&#xD;
&#xD;
                    3. using acceptable contraception and agree to exclude pregnancy with pregnancy&#xD;
                       test in the beginning of the hospitalization&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  - other coexisting severe chronic lung diseases&#xD;
&#xD;
          -  absolute contraindications to six-minute-walking-test according to&#xD;
&#xD;
        Polish Respiratory Society guidelines:&#xD;
&#xD;
          -  &lt; 7-10 days since coronary interventions due to STEMI&#xD;
&#xD;
          -  &lt; 24 h since planned coronary intervention&#xD;
&#xD;
          -  myocarditis/pericarditis&#xD;
&#xD;
          -  symptomatic rhythm and conduction abnormalities&#xD;
&#xD;
          -  acute deep vein thrombosis, pulmonary embolism, pulmonary infarction&#xD;
&#xD;
          -  decompensated heart failure&#xD;
&#xD;
          -  acute infection and other diseases which can significantly impact the test result (eg.&#xD;
             severe anemia, acute kidney or liver failure, hypo- or hyperthyroidism, etc)&#xD;
&#xD;
             - contraindications to morphine hydrochloride:&#xD;
&#xD;
          -  previous history of respiratory depression after opioid administration&#xD;
&#xD;
          -  previous history of allergic reactions to opioids&#xD;
&#xD;
          -  severe ventilation impairment due to e.g. asthmatic state, airway foreign body&#xD;
&#xD;
          -  severe kidney or liver failure&#xD;
&#xD;
          -  increased intracranial pressure&#xD;
&#xD;
          -  head injury&#xD;
&#xD;
          -  cerebral edema&#xD;
&#xD;
          -  coma&#xD;
&#xD;
          -  seizure disorders&#xD;
&#xD;
          -  acute alcohol poisoning&#xD;
&#xD;
          -  acute abdomen&#xD;
&#xD;
          -  acute diarrhea caused by infection or food poisoning;&#xD;
&#xD;
          -  patients at risk of paralytic ileus;&#xD;
&#xD;
          -  biliary colic;&#xD;
&#xD;
          -  phaeochromocytoma;&#xD;
&#xD;
          -  simultaneous MAO inhibitor treatment and immediate 2-week period following its&#xD;
             discontinuation - ongoing opioid treatment for any indication&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 25, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>July 30, 2020</last_update_submitted>
  <last_update_submitted_qc>July 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 4, 2020</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>Pulmonary Fibrosis</mesh_term>
    <mesh_term>Dyspnea</mesh_term>
    <mesh_term>Idiopathic Pulmonary Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Morphine</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/NCT04497831
org study id: NKBBN/433/2018
secondary id: 2019-000662-37
nct id: NCT04497831
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
"Determination of the effectiveness of nebulized morphine in the treatment of dyspnea in
      patients with advanced idiopathic pulmonary fibrosis"
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The study is a randomized, double-blind, placebo-controlled analysis conducted with crossover arms. The study consists of two treatment periods lasting a total of 5 days: 2 days of nebulization with 0.9% NaCl and 2 days of nebulization with 2.0% morphine hydrochloride solution separated by 1 day intended for elimination of the drug from the body (wash-out). The order of treatment periods (morphine -> placebo, placebo -> morphine) will be randomized for each patient by a hospital pharmacist using online software: Research Randomizer 4.0. The draw will assign the participant to one of two sequences:
A. 2 days - 0.9% NaCl; 1 day - wash-out; 2 days - morphine hydrochloride. B. 2 days - morphine hydrochloride; 1 day - wash-out; 2 days - 0.9% NaCl
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Double blind
measure: The primary end point is a reduction of breathlessness intensity by ≥20 mm at 100 mm visual analogue scale (VAS) after nebulization, during daily, normal activities
time frame: Breathlessness during daily, normal activities will be measured with VAS 1 hour before nebulization and 4 hours after
description: The primary end point is a reduction of breathlessness intensity by ≥20 mm at 100 mm visual analogue scale (VAS) after nebulization, during daily, normal activities
measure: Secondary end point
time frame: Cough and chest pain severity during normal activities will be assessed with VAS 1h before nebulization and 4 hours after Six minute walking test, along with breathlessness, cough and chest pain assessment in VAS, will be performed 1h before nebuli
description: Secondary end points are:
reduction of breathlessness intensity by ≥20 mm at 100 mm visual analogue scale (VAS) following six minute walking test (6MWT) performed after nebulization
improvement of 6MWT distance by ≥30 m
reduction of cough severity by ≥17 mm at 100 mm visual analogue scale (VAS) after nebulization, during normal activities
reduction of chest pain severity by ≥19 mm at 100 mm visual analogue scale (VAS) after nebulization, during normal activities
reduction of cough severity by ≥17 mm at 100 mm visual analogue scale (VAS) during six minute walking test (6MWT) performed after nebulization
reduction of chest pain severity by ≥19 mm at 100 mm visual analogue scale (VAS) following six minute walking test (6MWT) performed after nebulization
arm group label: Study Drug
arm group type: Experimental
description: Morphine hydrochloride
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Drug
intervention name: Morphine hydrochloride
description: 5 mg milligram(s) per day per two days of dosage
arm group label: Study Drug
intervention type: Drug
intervention name: Placebo
description: Inhalation use
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Sponsor
mesh term: Pulmonary Fibrosis
mesh term: Dyspnea
mesh term: Idiopathic Pulmonary Fibrosis
mesh term: Fibrosis
mesh term: Morphine