<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/NCT03018652</url>
  </required_header>
  <id_info>
    <org_study_id>IgPRx in AECOPD outpatient</org_study_id>
    <nct_id>NCT03018652</nct_id>
  </id_info>
  <brief_title>Feasibility and Safety of Immunoglobulin (Ig) Treatment in COPD Outpatients With Frequent Exacerbations: Pilot Study 1</brief_title>
  <official_title>Feasibility and Safety of Immunoglobulin (Ig) Treatment in COPD Outpatients With Frequent Exacerbations: Pilot Study 1</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ottawa Hospital Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ottawa Hospital Research Institute</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the&#xD;
      airways, associated with poor health status, functional disability, significant morbidity,&#xD;
      and increased risk of death. In Ontario, COPD is the leading cause of hospital admission and&#xD;
      readmission, and costs the health system approximately 3 billion dollars annually.&#xD;
      Individuals with COPD experience increased 'flare-up's' (acute exacerbations) as their&#xD;
      disease worsens, characterized by periods of increased shortness of breath, cough, phlegm&#xD;
      production, and weakness. Acute exacerbations of COPD (AECOPD) are most commonly caused by&#xD;
      viral or bacterial infections, and often require patients to seek attention at the emergency&#xD;
      room or hospital for treatment. Current treatments to prevent COPD exacerbations are only&#xD;
      modestly effective. New therapies are needed to improve the quality of life and clinical&#xD;
      outcomes for individuals living with COPD.&#xD;
&#xD;
      Previous research at our center has shown a favourable effect of an antibody treatment&#xD;
      (immunoglobulin) on the frequency of AECOPD, doctor visits, treatments, and hospitalizations&#xD;
      for COPD patients. However, rigorous studies with more patients are required to confirm this&#xD;
      effect.&#xD;
&#xD;
      The investigators propose a clinical trial to evaluate immunoglobulin treatment in&#xD;
      outpatients with frequent exacerbations. In this study the investigators will determine if&#xD;
      immunoglobulin treatment is feasible, safe, tolerable, and potentially effective in reducing&#xD;
      the frequency of acute exacerbations. If this study is feasible and potentially effective, it&#xD;
      will inform larger studies to confirm the therapeutic effect of immunoglobulin treatment, and&#xD;
      would be a major advance in care of COPD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      COPD is an incurable respiratory disease characterized by progressive decline in lung&#xD;
      function, shortness of breath, exercise limitation, poor health status, and increased&#xD;
      mortality. The World Health Organization cites Chronic Obstructive Pulmonary Disease (COPD)&#xD;
      as the third leading cause of death worldwide, and estimates suggest it currently affects 65&#xD;
      million people. COPD is a leading cause for hospital admission and readmission in North&#xD;
      America, and costs our health system 50 billion dollars annually.&#xD;
&#xD;
      Patients with COPD experience episodic flares of their disease, known as acute exacerbations&#xD;
      (AECOPD). AECOPD are characterized by increased cough, shortness of breath, sputum&#xD;
      production, weakness, and worsening airflow obstruction. There is also a high degree of&#xD;
      systemic inflammation and immune system activation during the exacerbation. As the severity&#xD;
      of COPD increases, the frequency of exacerbations increases as well. However, a major&#xD;
      predictor of recurrent exacerbations is a history of exacerbation.&#xD;
&#xD;
      COPD exacerbations have a significant impact on the individual patient and the health system.&#xD;
      Previous studies have shown that patients with exacerbations experience reductions in quality&#xD;
      of life, such as ability to engage in activities of daily living, a worsening of lung&#xD;
      function and an increased risk for mortality during and after the exacerbation period.&#xD;
      Exacerbation events often cause the patient to seek acute medical attention and admission to&#xD;
      hospital, which drives the high health care costs. History of hospital admission due to&#xD;
      AECOPD is the strongest risk factor for readmission for recurrent AECOPD within one year.&#xD;
      Hospitalization for AECOPD is also associated with lower 3-year survival (82.1%; 95% CI,&#xD;
      78.1% - 86.4%) as compared to COPD patients without history of hospitalization (92%; 95%CI,&#xD;
      90.8% - 93.3%) in the previous 3 years independent of the severity of airflow limitation. As&#xD;
      a result, research has focused on methods to prevent or reduce the frequency of acute&#xD;
      exacerbations, with expected positive impacts on patients and the health system.&#xD;
&#xD;
      Unfortunately, there is no cure for COPD, and highly effective therapies are currently&#xD;
      lacking. The current GOLD COPD guidelines recommend smoking cessation, exercise training,&#xD;
      maximal bronchodilator therapy, and influenza and pneumococcal vaccinations to try and&#xD;
      prevent exacerbations. In patients with frequent exacerbations, both chronic macrolide&#xD;
      therapy with azithromycin, N-acetylcysteine and roflumilast (a PDE-4 inhibitor) have been&#xD;
      shown to increase the time to next exacerbation. However, these therapies are only modestly&#xD;
      effective, and patients continue to experience exacerbations while on maximal therapy.&#xD;
      Further research into new therapeutics to prevent and reduce exacerbations is imperative. The&#xD;
      development of newer immunomodulatory agents as adjuvant therapy to prevent AECOPD has become&#xD;
      an area of intense investigation.&#xD;
&#xD;
      Prolonged steroid use is associated with hypogammaglobulinemia in asthmatic patients.&#xD;
      Patients with COPD have lower immunoglobulin G (IgG) levels compared to patients with other&#xD;
      lung diseases, independent of oral steroid use and age. However, recurrent exacerbations&#xD;
      still occur despite having normal baseline serum IgG (data not yet published). Intravenous&#xD;
      and subcutaneous immunoglobulins (IVIG and SCIG, respectively) are prepared from pooled&#xD;
      plasma from thousands of healthy blood donors. The large donor pool ensures a diversity of&#xD;
      antibody specificities to a wide spectrum of antigens and microbial pathogens. IVIG or SCIG&#xD;
      represents a privileged source of natural antibodies (NAb), which occur in the absence of&#xD;
      autoimmune disease or immunization. NAb are not only an immune defense against pathogens but&#xD;
      also have anti-inflammatory and immunomodulatory activities. Given the heightened systemic&#xD;
      and airway inflammatory activity in patients with COPD, their propensity to&#xD;
      infection-triggered exacerbations, and their suppressed mucosal or systemic immunity, the&#xD;
      anti-inflammatory, anti-infective and immunomodulatory effects of Ig preparations could be&#xD;
      beneficial for patients with COPD.&#xD;
&#xD;
      The investigators recently reported a retrospective single center self-interval analysis of&#xD;
      Ig treatment as adjunctive preventative treatment for AECOPD in 14 patients. Half (8&#xD;
      patients) had at least severe COPD by GOLD criteria. Ig treatment significantly reduced&#xD;
      moderate and severe AECOPD from 4.7 ± 3.1 to 0.6 ± 1.0 per patient-year. Number of&#xD;
      hospitalizations was markedly reduced from twelve in the year prior to one in the year&#xD;
      following Ig treatment initiation. Even though the median baseline IgG level in this study&#xD;
      cohort was 5.9 g/L (interquartile range 4.1 - 7.4), and 36% had IgG less than 5 g/L, the&#xD;
      clinical effect of Ig treatment in reducing moderate and severe AECOPD was consistent across&#xD;
      all cases. While this demonstrates some promise, prospective controlled studies are required&#xD;
      to determine if Ig treatment could have any impact on the frequency of COPD exacerbations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 11, 2018</start_date>
  <completion_date type="Actual">November 20, 2019</completion_date>
  <primary_completion_date type="Actual">November 20, 2019</primary_completion_date>
  <phase>Phase 2</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 (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recruitment</measure>
    <time_frame>52 weeks</time_frame>
    <description>Average number of patients being recruited per month. The study meets primary outcome if at least 4 patients can be recruited per month on average.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adherence and protocol compliance</measure>
    <time_frame>104 weeks</time_frame>
    <description>Number and percentage of recruited patients adhere to the allocated treatment and protocol. The investigators aim to achieve 80% adherence rate which is defined as at least 80% of patients adhere to 80% of allocated treatment and protocol</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE</measure>
    <time_frame>104 weeks</time_frame>
    <description>This will be assessed by documentation of adverse events in patients treated with Ig treatment versus control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients able to complete treatment</measure>
    <time_frame>104 weeks</time_frame>
    <description>The proportion of patients able to complete the treatment in the experimental arm during the study period versus in the control arm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy trend: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) rates</measure>
    <time_frame>104 weeks</time_frame>
    <description>AECOPD will be ascertained by monthly follow-up phone calls as well as questionnaires during study visits to detect inpatient/outpatient treatment for exacerbations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy trend: Health status</measure>
    <time_frame>104 weeks</time_frame>
    <description>Measured by the validated St. George Respiratory Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy trend: Quality of life</measure>
    <time_frame>104 weeks</time_frame>
    <description>Validated quality of life measurement tool - EuroWol EQ-5D-5L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy trend: % predicted FEV1</measure>
    <time_frame>104 weeks</time_frame>
    <description>FEV1 value will be measured using a hand held spirometer. FEV1 value will be recorded in Litres (L) and reported as a percent of their predicted value (using the NHANES III reference standards for predicted values</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy trend: FEV1/FVC</measure>
    <time_frame>104 weeks</time_frame>
    <description>FVC will be measured using a hand held spirometer, and will be recorded in Litres (L). Ratio of FEV1 and FVC will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy trend: Health services use</measure>
    <time_frame>104 weeks</time_frame>
    <description>Number of non-study physician visits, emergency department (ED) and hospital admissions over the twelve-month study period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy trend: Health care system cost</measure>
    <time_frame>104 weeks</time_frame>
    <description>Through the perspective of healthcare system, the cost of health services use and intervention will be measured. Intervention cost includes medication, staff, and equipment cost.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease (COPD)</condition>
  <arm_group>
    <arm_group_label>Intervention group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IVIG 0.5 g/kg, up to maximum of 80 grams will be given on the day of randomization and then every 4 ± 1 weeks for 44 weeks (Total 48 weeks) n=8</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal saline (0.9% NaCl) 5 mL/kg, up to maximum of 800 mL will be given on the day of randomization (this will match the volume of 0.5g/kg of IVIG product) and then every 4 ± 1 weeks for 44 weeks (Total 48 weeks) n=8</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intravenous immunoglobulin</intervention_name>
    <description>IVIG 0.5 g/kg, up to maximum of 80 grams will be given on the day of randomization and then every 4 ± 1 weeks for 44 weeks (Total 48 weeks)</description>
    <arm_group_label>Intervention group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal Saline</intervention_name>
    <description>5 mL/kg, up to maximum of 800 mL will be given on the day of randomization (this will match the volume of 0.5g/kg of IVIG product) and then every 4 ± 1 weeks for 44 weeks (Total 48 weeks)</description>
    <arm_group_label>Control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients with frequent exacerbations of COPD (clinically dominant COPD in the&#xD;
             case of multiple co-morbidities eg. bronchiectasis, interstitial lung disease,&#xD;
             congestive heart failure)&#xD;
&#xD;
          -  Confirmed diagnosis of COPD (bronchodilator FEV1/FVC ratio &lt;0.7 on spirometry within&#xD;
             previous 12 months)&#xD;
&#xD;
          -  Age &gt;40 years&#xD;
&#xD;
          -  &gt;10 pack year smoking history&#xD;
&#xD;
          -  Frequent COPD exacerbations in the previous 12 months before enrollment, defined by&#xD;
             one or both of the following:&#xD;
&#xD;
          -  Treatment as an outpatient with antibiotics or prednisone (physician diagnosed COPD&#xD;
             exacerbation) on 2 previous occasions OR&#xD;
&#xD;
          -  One hospitalization for COPD exacerbation (as defined by 2/3 of increased dyspnea,&#xD;
             sputum volume, or sputum purulence in patients with known airflow limitation)&#xD;
&#xD;
          -  Expected to live &gt; 12 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known severe hypersensitivity to immunoglobulin or its components (anaphylaxis)&#xD;
&#xD;
          -  Active or metastatic malignancy (including chronic lymphocytic leukemia) excluding&#xD;
             local skin cancers&#xD;
&#xD;
          -  History of hematopoietic stem cell transplant or solid organ transplant&#xD;
&#xD;
          -  Current treatment with a biological therapy for other conditions&#xD;
&#xD;
          -  Concomitant significant immunodeficiency or use of immunosuppressive treatment (other&#xD;
             than for COPD)&#xD;
&#xD;
          -  Alpha-1 antitrypsin deficiency (based on enzyme level from bloodwork)&#xD;
&#xD;
          -  Significant proteinuria (dipstick proteinuria ≥ 3+ AND known urinary protein loss ≥ 2&#xD;
             g/day or nephrotic syndrome) and/or has a history of acute renal failure and/or severe&#xD;
             renal impairment (creatinine more than 2.5 times the upper limit of normal and/or on&#xD;
             dialysis)&#xD;
&#xD;
          -  IgA deficiency (IgA &lt;0.1 g/L)&#xD;
&#xD;
          -  Immunoglobulin therapy in the last 12 months or on current Ig therapy or have a&#xD;
             clinical indication for Ig replacement therapy&#xD;
             (www.nacblood.ca/resources/guidelines/IVIG.html)&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>The Ottawa Hospital, General Campus</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1J 0J2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>December 16, 2016</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <last_update_submitted>November 25, 2019</last_update_submitted>
  <last_update_submitted_qc>November 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 26, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COPD</keyword>
  <keyword>Ig</keyword>
  <keyword>IPRAC</keyword>
  <keyword>outpatient</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Immunoglobulins, Intravenous</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>gamma-Globulins</mesh_term>
    <mesh_term>Rho(D) Immune Globulin</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/NCT03018652
org study id: IgPRx in AECOPD outpatient
nct id: NCT03018652
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the
      airways, associated with poor health status, functional disability, significant morbidity,
      and increased risk of death. In Ontario, COPD is the leading cause of hospital admission and
      readmission, and costs the health system approximately 3 billion dollars annually.
      Individuals with COPD experience increased 'flare-up's' (acute exacerbations) as their
      disease worsens, characterized by periods of increased shortness of breath, cough, phlegm
      production, and weakness. Acute exacerbations of COPD (AECOPD) are most commonly caused by
      viral or bacterial infections, and often require patients to seek attention at the emergency
      room or hospital for treatment. Current treatments to prevent COPD exacerbations are only
      modestly effective. New therapies are needed to improve the quality of life and clinical
      outcomes for individuals living with COPD.

      Previous research at our center has shown a favourable effect of an antibody treatment
      (immunoglobulin) on the frequency of AECOPD, doctor visits, treatments, and hospitalizations
      for COPD patients. However, rigorous studies with more patients are required to confirm this
      effect.

      The investigators propose a clinical trial to evaluate immunoglobulin treatment in
      outpatients with frequent exacerbations. In this study the investigators will determine if
      immunoglobulin treatment is feasible, safe, tolerable, and potentially effective in reducing
      the frequency of acute exacerbations. If this study is feasible and potentially effective, it
      will inform larger studies to confirm the therapeutic effect of immunoglobulin treatment, and
      would be a major advance in care of COPD.
COPD is an incurable respiratory disease characterized by progressive decline in lung
      function, shortness of breath, exercise limitation, poor health status, and increased
      mortality. The World Health Organization cites Chronic Obstructive Pulmonary Disease (COPD)
      as the third leading cause of death worldwide, and estimates suggest it currently affects 65
      million people. COPD is a leading cause for hospital admission and readmission in North
      America, and costs our health system 50 billion dollars annually.

      Patients with COPD experience episodic flares of their disease, known as acute exacerbations
      (AECOPD). AECOPD are characterized by increased cough, shortness of breath, sputum
      production, weakness, and worsening airflow obstruction. There is also a high degree of
      systemic inflammation and immune system activation during the exacerbation. As the severity
      of COPD increases, the frequency of exacerbations increases as well. However, a major
      predictor of recurrent exacerbations is a history of exacerbation.

      COPD exacerbations have a significant impact on the individual patient and the health system.
      Previous studies have shown that patients with exacerbations experience reductions in quality
      of life, such as ability to engage in activities of daily living, a worsening of lung
      function and an increased risk for mortality during and after the exacerbation period.
      Exacerbation events often cause the patient to seek acute medical attention and admission to
      hospital, which drives the high health care costs. History of hospital admission due to
      AECOPD is the strongest risk factor for readmission for recurrent AECOPD within one year.
      Hospitalization for AECOPD is also associated with lower 3-year survival (82.1%; 95% CI,
      78.1% - 86.4%) as compared to COPD patients without history of hospitalization (92%; 95%CI,
      90.8% - 93.3%) in the previous 3 years independent of the severity of airflow limitation. As
      a result, research has focused on methods to prevent or reduce the frequency of acute
      exacerbations, with expected positive impacts on patients and the health system.

      Unfortunately, there is no cure for COPD, and highly effective therapies are currently
      lacking. The current GOLD COPD guidelines recommend smoking cessation, exercise training,
      maximal bronchodilator therapy, and influenza and pneumococcal vaccinations to try and
      prevent exacerbations. In patients with frequent exacerbations, both chronic macrolide
      therapy with azithromycin, N-acetylcysteine and roflumilast (a PDE-4 inhibitor) have been
      shown to increase the time to next exacerbation. However, these therapies are only modestly
      effective, and patients continue to experience exacerbations while on maximal therapy.
      Further research into new therapeutics to prevent and reduce exacerbations is imperative. The
      development of newer immunomodulatory agents as adjuvant therapy to prevent AECOPD has become
      an area of intense investigation.

      Prolonged steroid use is associated with hypogammaglobulinemia in asthmatic patients.
      Patients with COPD have lower immunoglobulin G (IgG) levels compared to patients with other
      lung diseases, independent of oral steroid use and age. However, recurrent exacerbations
      still occur despite having normal baseline serum IgG (data not yet published). Intravenous
      and subcutaneous immunoglobulins (IVIG and SCIG, respectively) are prepared from pooled
      plasma from thousands of healthy blood donors. The large donor pool ensures a diversity of
      antibody specificities to a wide spectrum of antigens and microbial pathogens. IVIG or SCIG
      represents a privileged source of natural antibodies (NAb), which occur in the absence of
      autoimmune disease or immunization. NAb are not only an immune defense against pathogens but
      also have anti-inflammatory and immunomodulatory activities. Given the heightened systemic
      and airway inflammatory activity in patients with COPD, their propensity to
      infection-triggered exacerbations, and their suppressed mucosal or systemic immunity, the
      anti-inflammatory, anti-infective and immunomodulatory effects of Ig preparations could be
      beneficial for patients with COPD.

      The investigators recently reported a retrospective single center self-interval analysis of
      Ig treatment as adjunctive preventative treatment for AECOPD in 14 patients. Half (8
      patients) had at least severe COPD by GOLD criteria. Ig treatment significantly reduced
      moderate and severe AECOPD from 4.7 ± 3.1 to 0.6 ± 1.0 per patient-year. Number of
      hospitalizations was markedly reduced from twelve in the year prior to one in the year
      following Ig treatment initiation. Even though the median baseline IgG level in this study
      cohort was 5.9 g/L (interquartile range 4.1 - 7.4), and 36% had IgG less than 5 g/L, the
      clinical effect of Ig treatment in reducing moderate and severe AECOPD was consistent across
      all cases. While this demonstrates some promise, prospective controlled studies are required
      to determine if Ig treatment could have any impact on the frequency of COPD exacerbations.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Recruitment
time frame: 52 weeks
description: Average number of patients being recruited per month. The study meets primary outcome if at least 4 patients can be recruited per month on average.
measure: Adherence and protocol compliance
time frame: 104 weeks
description: Number and percentage of recruited patients adhere to the allocated treatment and protocol. The investigators aim to achieve 80% adherence rate which is defined as at least 80% of patients adhere to 80% of allocated treatment and protocol
measure: Number of participants with treatment-related adverse events as assessed by CTCAE
time frame: 104 weeks
description: This will be assessed by documentation of adverse events in patients treated with Ig treatment versus control
measure: Proportion of patients able to complete treatment
time frame: 104 weeks
description: The proportion of patients able to complete the treatment in the experimental arm during the study period versus in the control arm
measure: Efficacy trend: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) rates
time frame: 104 weeks
description: AECOPD will be ascertained by monthly follow-up phone calls as well as questionnaires during study visits to detect inpatient/outpatient treatment for exacerbations.
measure: Efficacy trend: Health status
time frame: 104 weeks
description: Measured by the validated St. George Respiratory Questionnaire
measure: Efficacy trend: Quality of life
time frame: 104 weeks
description: Validated quality of life measurement tool - EuroWol EQ-5D-5L
measure: Efficacy trend: % predicted FEV1
time frame: 104 weeks
description: FEV1 value will be measured using a hand held spirometer. FEV1 value will be recorded in Litres (L) and reported as a percent of their predicted value (using the NHANES III reference standards for predicted values
measure: Efficacy trend: FEV1/FVC
time frame: 104 weeks
description: FVC will be measured using a hand held spirometer, and will be recorded in Litres (L). Ratio of FEV1 and FVC will be reported.
measure: Efficacy trend: Health services use
time frame: 104 weeks
description: Number of non-study physician visits, emergency department (ED) and hospital admissions over the twelve-month study period.
measure: Efficacy trend: Health care system cost
time frame: 104 weeks
description: Through the perspective of healthcare system, the cost of health services use and intervention will be measured. Intervention cost includes medication, staff, and equipment cost.
arm group label: Intervention group
arm group type: Experimental
description: IVIG 0.5 g/kg, up to maximum of 80 grams will be given on the day of randomization and then every 4 ± 1 weeks for 44 weeks (Total 48 weeks) n=8
arm group label: Control group
arm group type: Placebo Comparator
description: Normal saline (0.9% NaCl) 5 mL/kg, up to maximum of 800 mL will be given on the day of randomization (this will match the volume of 0.5g/kg of IVIG product) and then every 4 ± 1 weeks for 44 weeks (Total 48 weeks) n=8
intervention type: Drug
intervention name: Intravenous immunoglobulin
description: IVIG 0.5 g/kg, up to maximum of 80 grams will be given on the day of randomization and then every 4 ± 1 weeks for 44 weeks (Total 48 weeks)
arm group label: Intervention group
intervention type: Drug
intervention name: Normal Saline
description: 5 mL/kg, up to maximum of 800 mL will be given on the day of randomization (this will match the volume of 0.5g/kg of IVIG product) and then every 4 ± 1 weeks for 44 weeks (Total 48 weeks)
arm group label: Control group
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Immunoglobulins
mesh term: Immunoglobulins, Intravenous
mesh term: Antibodies
mesh term: gamma-Globulins
mesh term: Rho(D) Immune Globulin