<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/NCT03751670</url>
  </required_header>
  <id_info>
    <org_study_id>SFRH/BD/147200/2019</org_study_id>
    <nct_id>NCT03751670</nct_id>
  </id_info>
  <brief_title>Pulmonary Rehabilitation During Acute Exacerbations of Chronic Obstructive Pulmonary Disease: a Mixed-methods Approach</brief_title>
  <official_title>Pulmonary Rehabilitation During Acute Exacerbations of Chronic Obstructive</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aveiro University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fundação para a Ciência e a Tecnologia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Aveiro University</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>
      This study aims to i) assess the short-, mid- and long-term effectiveness of a&#xD;
      patient-centred community-based pulmonary rehabilitation (PR) programme during during acute&#xD;
      exacerbations of chronic obstructive pulmonary disease (AECOPD); ii) establish the minimal&#xD;
      clinical important differences for PR in AECOPD for clinical and patient-reported outcome&#xD;
      measures; and iii) evaluate patients' perspectives and self-reported impact of the PR&#xD;
      programme.&#xD;
&#xD;
      Patients with AECOPD will be recruited via clinicians at hospitals and primary care centres.&#xD;
      Sociodemographic, anthropometric and clinical data; vital signs and peripheral oxygen&#xD;
      saturation; symptoms (dyspnoea, fatigue, cough and sputum); lung function; physical activity&#xD;
      level; peripheral muscle strength; functional status; exercise tolerance; impact of the&#xD;
      disease and health-related quality of life will be collected within 24h-48h of the AECOPD&#xD;
      diagnosis. Then, patients will be randomly allocated to either conventional treatment or&#xD;
      conventional treatment plus PR. After 3 weeks, all outcome measures will be reassessed.&#xD;
      Additionally, follow-ups at 2, 6 and 12 months will be performed through phone calls to&#xD;
      assess the number of recurrent AECOPD, healthcare utilization and mortality.&#xD;
&#xD;
      Conventional treatment will consist on daily medical treatment prescribed by the physician&#xD;
      (i.e., medication).&#xD;
&#xD;
      Community-based PR will involve 6 sessions (2 times per week) of breathing retraining and&#xD;
      airway clearance techniques, exercises for thoracic mobility, expansion and flexibility,&#xD;
      cardiorespiratory exercise training, education and psychosocial support.&#xD;
&#xD;
      It is expected that, by including PR in the treatment of patients with AECOPD, they will&#xD;
      express greater improvements in a shorter period of time and experience a decrease number of&#xD;
      re-exacerbations and healthcare utilization.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Acute exacerbations of COPD (AECOPD) negatively impact on patients' health status and disease&#xD;
      progression, and increase patients' susceptibility to exacerbations, hospitalizations and&#xD;
      death. Therefore, the treatment goals for patients with AECOPD are to minimize the negative&#xD;
      impact of these events and prevent their recurrence.&#xD;
&#xD;
      Pulmonary rehabilitation (PR) is the comprehensive intervention presenting the most&#xD;
      well-established benefits in patients with stable COPD, thus, it would seem reasonable to&#xD;
      consider PR as a management strategy for AECOPD. However, studies assessing PR role during&#xD;
      AECOPD have shown conflicting results.&#xD;
&#xD;
      Therefore, the main aim of this project is to assess the short-, mid- and long-term&#xD;
      effectiveness of a patient-centered community-based PR programme during AECOPD. Secondarily,&#xD;
      we aim to develop and implement a community-based PR programme for patients with AECOPD,&#xD;
      specifically tailored to their self-reported and clinical needs; establish the minimal&#xD;
      clinical important differences for PR in AECOPD for clinical and patient-reported outcome&#xD;
      measures; and evaluate patients' perspectives and self-reported impact of the PR programme.&#xD;
&#xD;
      A pilot study was performed between November 2016 and December 2017 to allow sample size&#xD;
      calculation and adjustments to the protocol of the randomized controlled trial. Based on this&#xD;
      pilot study, a sample size estimation was performed for the COPD Assessment Test to detect a&#xD;
      moderate effect size (f=0.30), with 80% power, 5% significance level and moderate correlation&#xD;
      among repeated measures (r=0.25). The minimum sample size estimation was 36 participants.&#xD;
      However, as in respiratory interventions dropout rates are around 30-35%, a total of 50&#xD;
      participants with AECOPD will be needed.&#xD;
&#xD;
      The plan is to recruit approximately 50 voluntary patients with AECOPD via clinicians at&#xD;
      hospitals and primary care centres. This study will enroll adult patients diagnosed with&#xD;
      AECOPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD)&#xD;
      criteria.&#xD;
&#xD;
      Patients will be recruited via the clinicians, who will provide a brief explanation about the&#xD;
      study and inform the researcher about interested participants. Then, the researcher will&#xD;
      contact interested participants and provide further information about the study, clarify any&#xD;
      doubts and collect the inform consents. Patients will be eligible if they are: i) diagnosed&#xD;
      with AECOPD according to the GOLD criteria; ii) included within 24-48h of the diagnostic; and&#xD;
      iii) able to provide informed consent. Exclusion criteria will include: i) need for&#xD;
      hospitalization; ii) other coexisting chronic respiratory diseases; iii) unstable&#xD;
      cardiovascular disease; iv) musculoskeletal or neuromuscular conditions that preclude the&#xD;
      performance of the assessments and/or treatment sessions; v) signs of cognitive impairment;&#xD;
      vi) current neoplasia or immunological disease and vii) any therapeutic intervention in&#xD;
      addition to standard of care.&#xD;
&#xD;
      Patients who agree to participate will be randomly allocated to the conventional treatment&#xD;
      group (control group) or the conventional treatment plus PR group (experimental group).&#xD;
&#xD;
      Baseline data will be collected within the first 24-48 hours of the diagnosis of AECOPD. The&#xD;
      researcher will collect sociodemographic, anthropometric and clinical data (e.g., number of&#xD;
      exacerbations in the previous year); vital signs and peripheral oxygen saturation; symptoms&#xD;
      (dyspnoea, fatigue, cough and sputum); lung function (spirometry); physical activity level;&#xD;
      peripheral muscle strength (handgrip and hand-held dynamometer); functional status; exercise&#xD;
      tolerance; impact of the disease and health-related quality of life.&#xD;
&#xD;
      Patients in the control group will receive daily medical treatment prescribed by the&#xD;
      physician (i.e., medication).&#xD;
&#xD;
      Patients in the experimental group will receive daily medical treatment plus a&#xD;
      community-based PR programme that will involve 6 sessions (2 times per week). The PR&#xD;
      programme will consist of breathing retraining and airway clearance techniques, exercises for&#xD;
      thoracic mobility, expansion and flexibility, cardiorespiratory exercise training, education&#xD;
      and psychosocial support. This programme will be adjusted to each individual needs. After&#xD;
      this period all measurements will be repeated. Furthermore, vital signs, peripheral oxygen&#xD;
      saturation, dyspnoea and fatigue will also be collected before/during/after each session to&#xD;
      monitor the intervention. Sessions will be conducted in properly equipped rooms or at&#xD;
      patients' home and will last approximately 60 minutes.&#xD;
&#xD;
      Additionally, after 2, 6 and 12 months, the researcher will contact all participants via&#xD;
      phone calls to collect data about the number of recurrent AECOPD, healthcare utilization&#xD;
      (e.g., unscheduled visits, hospitalizations) and mortality.&#xD;
&#xD;
      Data analysis will be undertaken using Statistical Package for the Social Sciences (SPSS)&#xD;
      software and will include descriptive and inferential statistics. To analyse changes in&#xD;
      outcome measures, data from baseline and after treatment assessments will be compare.&#xD;
      Moreover, between group comparisons will also be performed for baseline, after intervention&#xD;
      and follow-ups assessments. Effect sizes for the interventions will also be calculated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 1, 2018</start_date>
  <completion_date type="Anticipated">January 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2023</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>Participants are assigned to one of two groups in parallel for the duration of the study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>COPD Assessment test</measure>
    <time_frame>24-48 hours after hospital presentation or at clinical stabilization (baseline), after 3 weeks (after intervention) and after 2, 6 and 12 months at follow-ups.</time_frame>
    <description>Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) is a short, simple, multidimensional, easy to administer and disease-specific questionnaire that measures impact of the disease. CAT consists of eight items (i.e., cough, sputum, chest tightness, breathlessness going up hills/stairs, activity limitations at home, confidence leaving home, sleep and energy) scored from 0 to 5. The individual score of each item is added to provide a total score that can range from 0 to 40. Total scores inferior to 10 are considered as &quot;reduced impact&quot;, from 10-20 as &quot;medium impact&quot;, from 21- 30 as &quot;high impact&quot; and above 30 as &quot;very high impact&quot;. This is a valid and reliable instrument for use in patients with AECOPD (Chronbach's alpha=0.88).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Physical activity level</measure>
    <time_frame>assessment at baseline, after 3 weeks (after intervention) and after 2, 6 and 12 months at follow-ups</time_frame>
    <description>Patients' physical activity level will be assessed with the brief physical activity assessment tool, which is a simple, quick and reliable instrument that is being validated for use in COPD and has been significantly correlated with the international physical activity questionnaire (r=0.523, p&lt;0.001), accelerometers (r=0.529, p&lt;0.001) and daily steps (r=0.565, p&lt;0.001). It comprises two questions regarding the frequency and duration of moderate and vigorous physical activity undertaken in an usual week. Each question is scored from 0 to 4 and the total score consists of summing the result of the two questions, ranging from 0 to 8. Scores of 0-3 are considered &quot;insufficiently active&quot;, and scores higher or equal to 4 &quot;sufficiently active&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptoms of dyspnea</measure>
    <time_frame>assessment at baseline and after 3 weeks (after intervention)</time_frame>
    <description>Patients' self-reported level of dyspnea will be collected at rest, using the modified Borg scale. The level of dyspnea during activities will be collected with the modified British Medical Research Council questionnaire, which comprises five grades (statements) in a scale from 0 to 4, with higher grades indicating greater perceived respiratory limitation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptoms of fatigue</measure>
    <time_frame>assessment at baseline and after 3 weeks (after intervention)</time_frame>
    <description>Patients' self-reported level of fatigue will be collected at rest, using the modified Borg scale. The level of fatigue on a daily basis will be collected with the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Checklist of Individual Strength 8 (CIS-8).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung function measurement</measure>
    <time_frame>assessment at baseline and after 3 weeks (after intervention)</time_frame>
    <description>A spirometry test will be performed with a portable spirometer to assess the force expiratory volume in 1 second and, therefore, the degree of bronchial obstruction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in muscle strength</measure>
    <time_frame>assessment at baseline and after 3 weeks (after intervention)</time_frame>
    <description>Patients' handgrip, biceps and quadriceps muscle strength will be collected with a hand-held dynamometer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in functional status</measure>
    <time_frame>assessment at baseline and after 3 weeks (after intervention)</time_frame>
    <description>Patients' functional level will be assessed with the short physical performance battery, a simple and easy to perform tool that includes the four-meter gait speed test, the five-repetition sit-to-stand test and a balance test, and gives a total score based on the performance in each of those tests.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>1-minute sit-to-stand test</measure>
    <time_frame>assessment at baseline and after 3 weeks (after intervention)</time_frame>
    <description>The 1-minute sit-to-stand test will be used to also assess functional status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in exercise capacity</measure>
    <time_frame>assessment at baseline and after 3 weeks (after intervention)</time_frame>
    <description>Patients' exercise capacity will be assessed using the Chester step test, since it allows exercise prescription and is feasible in the community and at patients' home. Additionally, patients assessed in the community, at the facilities of University of Aveiro, will also perform the 6-minutes walk test to assess their exercise capacity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>London Chest Activities of Daily Living</measure>
    <time_frame>assessment at baseline and after 3 weeks (after intervention)</time_frame>
    <description>Patients' level of dyspnoea performing activities of daily living and functional status will be assessed with th London Chest Activities of Daily Living questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cough And Sputum Assessment Questionnaire</measure>
    <time_frame>assessment at baseline and after 3 weeks (after intervention)</time_frame>
    <description>Patients' symptoms of cough and sputum will be assessed with the Cough And Sputum Assessment Questionnaire (CASA-Q).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of hospitalizations</measure>
    <time_frame>assessment at baseline and after 2, 6 and 12 months from the end of the intervention (follow-ups)</time_frame>
    <description>Patients' number of hospitalizations in the previous year and during the follow-up period after the acute exacerbation will be assessed by asking the patient to self-report it.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Re-exacerbations</measure>
    <time_frame>assessment at baseline and after 2, 6 and 12 months from the end of the intervention (follow-ups)</time_frame>
    <description>Patients' number of re-exacerbations after being included in the study will be assessed by asking the patient to self-report it.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>assessment at baseline and after 2, 6 and 12 months from the end of the intervention (follow-ups)</time_frame>
    <description>The number of patients who died after the acute exacerbation, up to the 1 year follow-up period, will be collected.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Body mass index</measure>
    <time_frame>assessment at baseline</time_frame>
    <description>Patients' body mass index will be assessed in kg/m^2 based on patients' height and weight.</description>
  </other_outcome>
  <other_outcome>
    <measure>Heart rate</measure>
    <time_frame>assessment at baseline and 3 weeks after intervention</time_frame>
    <description>Heart rate will be assessed in beats per minute using a oximeter and blood pressure meter.</description>
  </other_outcome>
  <other_outcome>
    <measure>Respiratory rate</measure>
    <time_frame>assessment at baseline and 3 weeks after intervention</time_frame>
    <description>Respiratory rate will be assessed by direct observation, counting the number of respiratory cycles.</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood pressure</measure>
    <time_frame>assessment at baseline and 3 weeks after intervention</time_frame>
    <description>Blood pressure will be assessed using a blood pressure meter.</description>
  </other_outcome>
  <other_outcome>
    <measure>Peripheral Oxygen Saturation</measure>
    <time_frame>assessment at baseline and 3 weeks after intervention</time_frame>
    <description>Peripheral oxygen saturation will be assessed with a pulse oximeter.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Acute Exacerbation of Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>PR+conventional treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated with daily medication prescribed by the physician. Additionally, patients will receive 6 sessions (2 times a week during 3 weeks) of Pulmonary Rehabilitation (PR). PR will include breathing retraining and airway clearance techniques, exercises for thoracic mobility, expansion and flexibility, cardiorespiratory exercise training, education and psychosocial support.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will be treated with daily medication prescribed by the physician.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pulmonary Rehabilitation</intervention_name>
    <description>Pulmonary Rehabilitation programmes will include breathing retraining and airway clearance techniques, exercises for thoracic mobility, muscle strength, cardiorespiratory exercise training, education and psychosocial support.</description>
    <arm_group_label>PR+conventional treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Daily medical treatment</intervention_name>
    <description>Patients will be treated with daily medication prescribed by the physician.</description>
    <arm_group_label>Conventional treatment</arm_group_label>
    <arm_group_label>PR+conventional treatment</arm_group_label>
    <other_name>Medication</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  clinical diagnosis of AECOPD according to the Global Initiative for Chronic&#xD;
             Obstructive Lung Disease (GOLD) criteria (i.e., an episode of acute worsening of&#xD;
             respiratory symptoms that result in additional therapy);&#xD;
&#xD;
          -  included within 24-48h of the diagnostic;&#xD;
&#xD;
          -  able to provide their own informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  need for hospitalization;&#xD;
&#xD;
          -  other coexisting chronic respiratory diseases;&#xD;
&#xD;
          -  unstable cardiovascular disease;&#xD;
&#xD;
          -  presence of musculoskeletal or neuromuscular conditions that preclude the performance&#xD;
             of any of the assessments or the participation in the treatment sessions;&#xD;
&#xD;
          -  signs of cognitive impairment;&#xD;
&#xD;
          -  current neoplasia or immunological disease;&#xD;
&#xD;
          -  any therapeutic intervention in addition to standard of care.&#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>Alda S. Marques, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>School of Health Sciences of the University of Aveiro (ESSUA)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Aveiro</name>
      <address>
        <city>Aveiro</city>
        <zip>3810-193</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Portugal</country>
  </location_countries>
  <reference>
    <citation>Oliveira A, Machado A, Marques A. Minimal Important and Detectable Differences of Respiratory Measures in Outpatients with AECOPDdagger. COPD. 2018 Oct;15(5):479-488. doi: 10.1080/15412555.2018.1537366. Epub 2018 Dec 4.</citation>
    <PMID>30512981</PMID>
  </reference>
  <reference>
    <citation>Oliveira A, Marques A. Understanding symptoms variability in outpatients with AECOPD. Pulmonology. 2018 Nov-Dec;24(6):357-360. doi: 10.1016/j.pulmoe.2018.09.007. No abstract available.</citation>
    <PMID>30554671</PMID>
  </reference>
  <reference>
    <citation>Oliveira A, Afreixo V, Marques A. Enhancing our understanding of the time course of acute exacerbations of COPD managed on an outpatient basis. Int J Chron Obstruct Pulmon Dis. 2018 Nov 20;13:3759-3766. doi: 10.2147/COPD.S175890. eCollection 2018.</citation>
    <PMID>30538438</PMID>
  </reference>
  <reference>
    <citation>Oliveira AL, Marques AS. Outcome Measures Used in Pulmonary Rehabilitation in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review. Phys Ther. 2018 Mar 1;98(3):191-204. doi: 10.1093/ptj/pzx122.</citation>
    <PMID>29228288</PMID>
  </reference>
  <reference>
    <citation>Oliveira A, Marques A. Exploratory mixed methods study of respiratory physiotherapy for patients with lower respiratory tract infections. Physiotherapy. 2016 Mar;102(1):111-8. doi: 10.1016/j.physio.2015.03.3723. Epub 2015 May 14.</citation>
    <PMID>26067286</PMID>
  </reference>
  <reference>
    <citation>Oliveira A, Pinho C, Marques A. Effects of a respiratory physiotherapy session in patients with LRTI: a pre/post-test study. Clin Respir J. 2017 Nov;11(6):703-712. doi: 10.1111/crj.12402. Epub 2015 Nov 5.</citation>
    <PMID>26471240</PMID>
  </reference>
  <reference>
    <citation>Machado A, Oliveira A, Valente C, Burtin C, Marques A (2018) &quot;Community-based pulmonary rehabilitation during acute exacerbations of COPD&quot; European Respiratory Journal</citation>
  </reference>
  <reference>
    <citation>Machado A, Matos Silva P, Afreixo V, Caneiras C, Burtin C, Marques A. Design of pulmonary rehabilitation programmes during acute exacerbations of COPD: a systematic review and network meta-analysis. Eur Respir Rev. 2020 Nov 18;29(158):200039. doi: 10.1183/16000617.0039-2020. Print 2020 Dec 31. Erratum In: Eur Respir Rev. 2021 Feb 9;30(159):</citation>
    <PMID>33208486</PMID>
  </reference>
  <reference>
    <citation>Oliveira A, Rebelo P, Andrade L, Valente C, Marques A (2018) &quot;Computerised respiratory sounds during acute exacerbations of Chronic Obstructive Pulmonary Disease&quot;. Proceedings of the 4th IPLeiria's International Health Congress. BMC Health Services Research 2018, 18(Suppl 2): O23 pp 13</citation>
  </reference>
  <reference>
    <citation>Machado A, Oliveira A, Paixão C, Miranda S, Melro H, Ferreira D, Marques A (2017) &quot;Pulmonary rehabilitation effects on computerized respiratory sounds of patients with AECOPD&quot; Proceedings of the 42nd Annual Conference of the International Lung Sound Association, 182:57</citation>
  </reference>
  <reference>
    <citation>Machado A, Oliveira A, Valente C, Burtin C, Marques A. Effects of a community-based pulmonary rehabilitation programme during acute exacerbations of chronic obstructive pulmonary disease - A quasi-experimental pilot study. Pulmonology. 2020 Jan-Feb;26(1):27-38. doi: 10.1016/j.pulmoe.2019.05.004. Epub 2019 Jun 1.</citation>
    <PMID>31164288</PMID>
  </reference>
  <reference>
    <citation>Machado A, Oliveira A, Valente C, Burtin C, Marques A. Effects of a community-based pulmonary rehabilitation programme during acute exacerbations of chronic obstructive pulmonary disease - A quasi-experimental pilot study. Authors' reply. Pulmonology. 2020 Mar-Apr;26(2):112-113. doi: 10.1016/j.pulmoe.2019.09.001. Epub 2019 Oct 8. No abstract available.</citation>
    <PMID>31601490</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>November 13, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>March 7, 2023</last_update_submitted>
  <last_update_submitted_qc>March 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Aveiro University</investigator_affiliation>
    <investigator_full_name>Alda Sofia Pires de Dias Marques</investigator_full_name>
    <investigator_title>Senior Lecturer</investigator_title>
  </responsible_party>
  <keyword>Acute exacerbation of chronic obstructive pulmonary disease</keyword>
  <keyword>Pulmonary rehabilitation</keyword>
  <keyword>Community</keyword>
  <keyword>Home</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_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/NCT03751670
org study id: SFRH/BD/147200/2019
nct id: NCT03751670
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aims to i) assess the short-, mid- and long-term effectiveness of a
      patient-centred community-based pulmonary rehabilitation (PR) programme during during acute
      exacerbations of chronic obstructive pulmonary disease (AECOPD); ii) establish the minimal
      clinical important differences for PR in AECOPD for clinical and patient-reported outcome
      measures; and iii) evaluate patients' perspectives and self-reported impact of the PR
      programme.

      Patients with AECOPD will be recruited via clinicians at hospitals and primary care centres.
      Sociodemographic, anthropometric and clinical data; vital signs and peripheral oxygen
      saturation; symptoms (dyspnoea, fatigue, cough and sputum); lung function; physical activity
      level; peripheral muscle strength; functional status; exercise tolerance; impact of the
      disease and health-related quality of life will be collected within 24h-48h of the AECOPD
      diagnosis. Then, patients will be randomly allocated to either conventional treatment or
      conventional treatment plus PR. After 3 weeks, all outcome measures will be reassessed.
      Additionally, follow-ups at 2, 6 and 12 months will be performed through phone calls to
      assess the number of recurrent AECOPD, healthcare utilization and mortality.

      Conventional treatment will consist on daily medical treatment prescribed by the physician
      (i.e., medication).

      Community-based PR will involve 6 sessions (2 times per week) of breathing retraining and
      airway clearance techniques, exercises for thoracic mobility, expansion and flexibility,
      cardiorespiratory exercise training, education and psychosocial support.

      It is expected that, by including PR in the treatment of patients with AECOPD, they will
      express greater improvements in a shorter period of time and experience a decrease number of
      re-exacerbations and healthcare utilization.
Acute exacerbations of COPD (AECOPD) negatively impact on patients' health status and disease
      progression, and increase patients' susceptibility to exacerbations, hospitalizations and
      death. Therefore, the treatment goals for patients with AECOPD are to minimize the negative
      impact of these events and prevent their recurrence.

      Pulmonary rehabilitation (PR) is the comprehensive intervention presenting the most
      well-established benefits in patients with stable COPD, thus, it would seem reasonable to
      consider PR as a management strategy for AECOPD. However, studies assessing PR role during
      AECOPD have shown conflicting results.

      Therefore, the main aim of this project is to assess the short-, mid- and long-term
      effectiveness of a patient-centered community-based PR programme during AECOPD. Secondarily,
      we aim to develop and implement a community-based PR programme for patients with AECOPD,
      specifically tailored to their self-reported and clinical needs; establish the minimal
      clinical important differences for PR in AECOPD for clinical and patient-reported outcome
      measures; and evaluate patients' perspectives and self-reported impact of the PR programme.

      A pilot study was performed between November 2016 and December 2017 to allow sample size
      calculation and adjustments to the protocol of the randomized controlled trial. Based on this
      pilot study, a sample size estimation was performed for the COPD Assessment Test to detect a
      moderate effect size (f=0.30), with 80% power, 5% significance level and moderate correlation
      among repeated measures (r=0.25). The minimum sample size estimation was 36 participants.
      However, as in respiratory interventions dropout rates are around 30-35%, a total of 50
      participants with AECOPD will be needed.

      The plan is to recruit approximately 50 voluntary patients with AECOPD via clinicians at
      hospitals and primary care centres. This study will enroll adult patients diagnosed with
      AECOPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD)
      criteria.

      Patients will be recruited via the clinicians, who will provide a brief explanation about the
      study and inform the researcher about interested participants. Then, the researcher will
      contact interested participants and provide further information about the study, clarify any
      doubts and collect the inform consents. Patients will be eligible if they are: i) diagnosed
      with AECOPD according to the GOLD criteria; ii) included within 24-48h of the diagnostic; and
      iii) able to provide informed consent. Exclusion criteria will include: i) need for
      hospitalization; ii) other coexisting chronic respiratory diseases; iii) unstable
      cardiovascular disease; iv) musculoskeletal or neuromuscular conditions that preclude the
      performance of the assessments and/or treatment sessions; v) signs of cognitive impairment;
      vi) current neoplasia or immunological disease and vii) any therapeutic intervention in
      addition to standard of care.

      Patients who agree to participate will be randomly allocated to the conventional treatment
      group (control group) or the conventional treatment plus PR group (experimental group).

      Baseline data will be collected within the first 24-48 hours of the diagnosis of AECOPD. The
      researcher will collect sociodemographic, anthropometric and clinical data (e.g., number of
      exacerbations in the previous year); vital signs and peripheral oxygen saturation; symptoms
      (dyspnoea, fatigue, cough and sputum); lung function (spirometry); physical activity level;
      peripheral muscle strength (handgrip and hand-held dynamometer); functional status; exercise
      tolerance; impact of the disease and health-related quality of life.

      Patients in the control group will receive daily medical treatment prescribed by the
      physician (i.e., medication).

      Patients in the experimental group will receive daily medical treatment plus a
      community-based PR programme that will involve 6 sessions (2 times per week). The PR
      programme will consist of breathing retraining and airway clearance techniques, exercises for
      thoracic mobility, expansion and flexibility, cardiorespiratory exercise training, education
      and psychosocial support. This programme will be adjusted to each individual needs. After
      this period all measurements will be repeated. Furthermore, vital signs, peripheral oxygen
      saturation, dyspnoea and fatigue will also be collected before/during/after each session to
      monitor the intervention. Sessions will be conducted in properly equipped rooms or at
      patients' home and will last approximately 60 minutes.

      Additionally, after 2, 6 and 12 months, the researcher will contact all participants via
      phone calls to collect data about the number of recurrent AECOPD, healthcare utilization
      (e.g., unscheduled visits, hospitalizations) and mortality.

      Data analysis will be undertaken using Statistical Package for the Social Sciences (SPSS)
      software and will include descriptive and inferential statistics. To analyse changes in
      outcome measures, data from baseline and after treatment assessments will be compare.
      Moreover, between group comparisons will also be performed for baseline, after intervention
      and follow-ups assessments. Effect sizes for the interventions will also be calculated.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants are assigned to one of two groups in parallel for the duration of the study.
primary purpose: Treatment
masking: None (Open Label)
measure: COPD Assessment test
time frame: 24-48 hours after hospital presentation or at clinical stabilization (baseline), after 3 weeks (after intervention) and after 2, 6 and 12 months at follow-ups.
description: Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) is a short, simple, multidimensional, easy to administer and disease-specific questionnaire that measures impact of the disease. CAT consists of eight items (i.e., cough, sputum, chest tightness, breathlessness going up hills/stairs, activity limitations at home, confidence leaving home, sleep and energy) scored from 0 to 5. The individual score of each item is added to provide a total score that can range from 0 to 40. Total scores inferior to 10 are considered as "reduced impact", from 10-20 as "medium impact", from 21- 30 as "high impact" and above 30 as "very high impact". This is a valid and reliable instrument for use in patients with AECOPD (Chronbach's alpha=0.88).
measure: Physical activity level
time frame: assessment at baseline, after 3 weeks (after intervention) and after 2, 6 and 12 months at follow-ups
description: Patients' physical activity level will be assessed with the brief physical activity assessment tool, which is a simple, quick and reliable instrument that is being validated for use in COPD and has been significantly correlated with the international physical activity questionnaire (r=0.523, p<0.001), accelerometers (r=0.529, p<0.001) and daily steps (r=0.565, p<0.001). It comprises two questions regarding the frequency and duration of moderate and vigorous physical activity undertaken in an usual week. Each question is scored from 0 to 4 and the total score consists of summing the result of the two questions, ranging from 0 to 8. Scores of 0-3 are considered "insufficiently active", and scores higher or equal to 4 "sufficiently active".
measure: Symptoms of dyspnea
time frame: assessment at baseline and after 3 weeks (after intervention)
description: Patients' self-reported level of dyspnea will be collected at rest, using the modified Borg scale. The level of dyspnea during activities will be collected with the modified British Medical Research Council questionnaire, which comprises five grades (statements) in a scale from 0 to 4, with higher grades indicating greater perceived respiratory limitation.
measure: Symptoms of fatigue
time frame: assessment at baseline and after 3 weeks (after intervention)
description: Patients' self-reported level of fatigue will be collected at rest, using the modified Borg scale. The level of fatigue on a daily basis will be collected with the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Checklist of Individual Strength 8 (CIS-8).
measure: Lung function measurement
time frame: assessment at baseline and after 3 weeks (after intervention)
description: A spirometry test will be performed with a portable spirometer to assess the force expiratory volume in 1 second and, therefore, the degree of bronchial obstruction.
measure: Change in muscle strength
time frame: assessment at baseline and after 3 weeks (after intervention)
description: Patients' handgrip, biceps and quadriceps muscle strength will be collected with a hand-held dynamometer.
measure: Change in functional status
time frame: assessment at baseline and after 3 weeks (after intervention)
description: Patients' functional level will be assessed with the short physical performance battery, a simple and easy to perform tool that includes the four-meter gait speed test, the five-repetition sit-to-stand test and a balance test, and gives a total score based on the performance in each of those tests.
measure: 1-minute sit-to-stand test
time frame: assessment at baseline and after 3 weeks (after intervention)
description: The 1-minute sit-to-stand test will be used to also assess functional status.
measure: Change in exercise capacity
time frame: assessment at baseline and after 3 weeks (after intervention)
description: Patients' exercise capacity will be assessed using the Chester step test, since it allows exercise prescription and is feasible in the community and at patients' home. Additionally, patients assessed in the community, at the facilities of University of Aveiro, will also perform the 6-minutes walk test to assess their exercise capacity.
measure: London Chest Activities of Daily Living
time frame: assessment at baseline and after 3 weeks (after intervention)
description: Patients' level of dyspnoea performing activities of daily living and functional status will be assessed with th London Chest Activities of Daily Living questionnaire.
measure: Cough And Sputum Assessment Questionnaire
time frame: assessment at baseline and after 3 weeks (after intervention)
description: Patients' symptoms of cough and sputum will be assessed with the Cough And Sputum Assessment Questionnaire (CASA-Q).
measure: Number of hospitalizations
time frame: assessment at baseline and after 2, 6 and 12 months from the end of the intervention (follow-ups)
description: Patients' number of hospitalizations in the previous year and during the follow-up period after the acute exacerbation will be assessed by asking the patient to self-report it.
measure: Re-exacerbations
time frame: assessment at baseline and after 2, 6 and 12 months from the end of the intervention (follow-ups)
description: Patients' number of re-exacerbations after being included in the study will be assessed by asking the patient to self-report it.
measure: Mortality
time frame: assessment at baseline and after 2, 6 and 12 months from the end of the intervention (follow-ups)
description: The number of patients who died after the acute exacerbation, up to the 1 year follow-up period, will be collected.
measure: Body mass index
time frame: assessment at baseline
description: Patients' body mass index will be assessed in kg/m^2 based on patients' height and weight.
measure: Heart rate
time frame: assessment at baseline and 3 weeks after intervention
description: Heart rate will be assessed in beats per minute using a oximeter and blood pressure meter.
measure: Respiratory rate
time frame: assessment at baseline and 3 weeks after intervention
description: Respiratory rate will be assessed by direct observation, counting the number of respiratory cycles.
measure: Blood pressure
time frame: assessment at baseline and 3 weeks after intervention
description: Blood pressure will be assessed using a blood pressure meter.
measure: Peripheral Oxygen Saturation
time frame: assessment at baseline and 3 weeks after intervention
description: Peripheral oxygen saturation will be assessed with a pulse oximeter.
arm group label: PR+conventional treatment
arm group type: Experimental
description: Patients will be treated with daily medication prescribed by the physician. Additionally, patients will receive 6 sessions (2 times a week during 3 weeks) of Pulmonary Rehabilitation (PR). PR will include breathing retraining and airway clearance techniques, exercises for thoracic mobility, expansion and flexibility, cardiorespiratory exercise training, education and psychosocial support.
arm group label: Conventional treatment
arm group type: Active Comparator
description: Patients will be treated with daily medication prescribed by the physician.
intervention type: Other
intervention name: Pulmonary Rehabilitation
description: Pulmonary Rehabilitation programmes will include breathing retraining and airway clearance techniques, exercises for thoracic mobility, muscle strength, cardiorespiratory exercise training, education and psychosocial support.
arm group label: PR+conventional treatment
intervention type: Drug
intervention name: Daily medical treatment
description: Patients will be treated with daily medication prescribed by the physician.
arm group label: Conventional treatment
arm group label: PR+conventional treatment
other name: Medication
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alda S. Marques, PhD
role: Principal Investigator
affiliation: School of Health Sciences of the University of Aveiro (ESSUA)
facility: 
country: Portugal
citation: Oliveira A, Machado A, Marques A. Minimal Important and Detectable Differences of Respiratory Measures in Outpatients with AECOPDdagger. COPD. 2018 Oct;15(5):479-488. doi: 10.1080/15412555.2018.1537366. Epub 2018 Dec 4.
PMID: 30512981
citation: Oliveira A, Marques A. Understanding symptoms variability in outpatients with AECOPD. Pulmonology. 2018 Nov-Dec;24(6):357-360. doi: 10.1016/j.pulmoe.2018.09.007. No abstract available.
PMID: 30554671
citation: Oliveira A, Afreixo V, Marques A. Enhancing our understanding of the time course of acute exacerbations of COPD managed on an outpatient basis. Int J Chron Obstruct Pulmon Dis. 2018 Nov 20;13:3759-3766. doi: 10.2147/COPD.S175890. eCollection 2018.
PMID: 30538438
citation: Oliveira AL, Marques AS. Outcome Measures Used in Pulmonary Rehabilitation in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review. Phys Ther. 2018 Mar 1;98(3):191-204. doi: 10.1093/ptj/pzx122.
PMID: 29228288
citation: Oliveira A, Marques A. Exploratory mixed methods study of respiratory physiotherapy for patients with lower respiratory tract infections. Physiotherapy. 2016 Mar;102(1):111-8. doi: 10.1016/j.physio.2015.03.3723. Epub 2015 May 14.
PMID: 26067286
citation: Oliveira A, Pinho C, Marques A. Effects of a respiratory physiotherapy session in patients with LRTI: a pre/post-test study. Clin Respir J. 2017 Nov;11(6):703-712. doi: 10.1111/crj.12402. Epub 2015 Nov 5.
PMID: 26471240
citation: Machado A, Oliveira A, Valente C, Burtin C, Marques A (2018) "Community-based pulmonary rehabilitation during acute exacerbations of COPD" European Respiratory Journal
citation: Machado A, Matos Silva P, Afreixo V, Caneiras C, Burtin C, Marques A. Design of pulmonary rehabilitation programmes during acute exacerbations of COPD: a systematic review and network meta-analysis. Eur Respir Rev. 2020 Nov 18;29(158):200039. doi: 10.1183/16000617.0039-2020. Print 2020 Dec 31. Erratum In: Eur Respir Rev. 2021 Feb 9;30(159):
PMID: 33208486
citation: Oliveira A, Rebelo P, Andrade L, Valente C, Marques A (2018) "Computerised respiratory sounds during acute exacerbations of Chronic Obstructive Pulmonary Disease". Proceedings of the 4th IPLeiria's International Health Congress. BMC Health Services Research 2018, 18(Suppl 2): O23 pp 13
citation: Machado A, Oliveira A, Paixão C, Miranda S, Melro H, Ferreira D, Marques A (2017) "Pulmonary rehabilitation effects on computerized respiratory sounds of patients with AECOPD" Proceedings of the 42nd Annual Conference of the International Lung Sound Association, 182:57
citation: Machado A, Oliveira A, Valente C, Burtin C, Marques A. Effects of a community-based pulmonary rehabilitation programme during acute exacerbations of chronic obstructive pulmonary disease - A quasi-experimental pilot study. Pulmonology. 2020 Jan-Feb;26(1):27-38. doi: 10.1016/j.pulmoe.2019.05.004. Epub 2019 Jun 1.
PMID: 31164288
citation: Machado A, Oliveira A, Valente C, Burtin C, Marques A. Effects of a community-based pulmonary rehabilitation programme during acute exacerbations of chronic obstructive pulmonary disease - A quasi-experimental pilot study. Authors' reply. Pulmonology. 2020 Mar-Apr;26(2):112-113. doi: 10.1016/j.pulmoe.2019.09.001. Epub 2019 Oct 8. No abstract available.
PMID: 31601490
responsible party type: Principal Investigator
investigator affiliation: Aveiro University
investigator full name: Alda Sofia Pires de Dias Marques
investigator title: Senior Lecturer
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
sharing ipd: No