Ig PRx in AECOPD: Pilot Study

Study Overview
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Brief Summary
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This study will look at immunoglobulin (Ig) treatment in hospitalized chronic obstructive lung disease (COPD) patients with frequent exacerbations. This is a Phase II, pilot randomized double blind control study, meaning this study will help assess if this research can be expanded to evaluate Ig treatment in patients with COPD. Ig treatment is a sterile solution of human immunoglobulin proteins given intravenously (in the vein). Immunoglobulins are part of the immune system and help the body fight infections. Participants will be assigned to either receiving the Ig treatment or normal saline as a control product every 4 weeks for 12 months. Participants will continue on current standard therapy as determined by their treating physician.

Official Title
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Feasibility and Safety of Immunoglobulin (Ig) Prophylactic Treatment in COPD Patients With Frequent Exacerbations: A Pilot Study

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Intravenous immunoglobulin (IVIG)
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalized adult patient with AECOPD (clinically dominant AECOPD in the case of multiple co-morbidities eg. absence of overt lobar pneumonia or acute congestive heart failure or alternate diagnosis such as acute coronary syndrome or pulmonary embolism) Diagnosis of severe COPD (post bronchodilator FEV1 <50%, FEV1/FVC ratio <0.7) made by standard spirometry within previous 12 months or within three days of admission if previous PFT data is not available Age >40 years >10 pack year smoking history At least one COPD exacerbation in the previous 12 months before enrollment, defined by having had documented inpatient or outpatient treatment by physician with antibiotics and/or prednisone for physician diagnosed COPD exacerbation Expected to live > 12 months Exclusion Criteria: Known severe hypersensitivity to immunoglobulin or its components (anaphylaxis) Underlying malignancy (including chronic lymphocytic leukemia) History of hematopoietic stem cell transplant or solid organ transplant Current treatment with a biological therapy for other conditions Concomitant significant immunodeficiency or on immunosuppressive treatment other than for COPD Alpha-1 antitrypsin deficiency Significant proteinuria (dipstick proteinuria ≥ 3+ or known urinary protein loss ≥ 2 g/day or nephrotic syndrome) and/or has acute renal failure and/or severe renal impairment (creatinine more than 2.5 times the upper limit of normal and/or on dialysis) IgA deficiency (IgA <0.1 g/L) Immunoglobulin therapy in the last 12 months or on current Ig therapy or have a clinical indication for Ig replacement therapy (www.nacblood.ca/resources/guidelines/IVIG.html) Obesity (BMI ≥35 kg/m²) Pregnancy

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Arm 1: Treatment<br>Baseline Ig < 7g/L group - Intravenous immunoglobulin (IVIG) 0.8 g/kg will be given within 12 hours after randomization during hospital admission and then every 4 weeks for 44 weeks (total 48 weeks). Baseline Ig > or = 7 g/L group - Intravenous immunoglobulin (IVIG) 0.5 g/kg will be given within 12 hours after randomization during hospital admission and then every 4 weeks for 44 weeks (total 48 weeks). | Drug: Intravenous immunoglobulin (IVIG)<br>* Baseline Ig < 7g/L group - Intravenous immunoglobulin (IVIG) 0.8 g/kg will be given within 12 hours after randomization. Baseline Ig > or = 7 g/L group - Intravenous immunoglobulin (IVIG) 0.5 g/kg will be given within 12 hours after randomization<br>* Other names: Octagam;|
| Active Comparator: Intervention Arm 2: Control<br>Baseline Ig < 7g/L group - Normal Saline (0.9% NaCl) 8 mL/kg will be given within 12 hours after randomization during hospital admission and then every 4 weeks for 44 weeks (total 48 weeks). Baseline Ig > or = 7 g/L group - Normal Saline (0.9% NaCl) 5 mL/kg will be given within 12 hours after randomization during hospital admission and then every 4 weeks for 44 weeks (total 48 weeks). | Drug: Normal Saline<br>* Baseline Ig < 7g/L group - Normal Saline (0.9% NaCl) 8 mL/kg will be given within 12 hours after randomization. Baseline Ig > or = 7 g/L group - Normal Saline (0.9% NaCl) 5 mL/kg will be given within 12 hours after randomization<br>* Other names: Sodium Chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment | 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. | 52 weeks | 
| Adherence and protocol compliance | Number and percentage of recruited patients adhere to the allocated treatment and protocol. We aim to achieve 80% adherence rate which is defined as at least 80% of patients adhere to 80% of allocated treatment and protocol | 104 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE | This will be assessed by documentation of adverse events in patients treated with Ig treatment versus control | 104 weeks | 
| Tolerability of treatment | The proportion of patients able to complete the treatment in the experimental arm during the study period versus in the control arm | 104 weeks | 
| Efficacy trend: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) rates | AECOPD will be ascertained by monthly follow-up phone calls as well as questionnaires during study visits to detect inpatient/outpatient treatment for exacerbations. | 104 weeks | 
| Efficacy trend: Health status | measured by the validated St. George Respiratory Questionnaire | 104 weeks | 
| Efficacy trend: Quality of life | validated quality of life measurement tool - EuroWol EQ-5D-5L | 104 weeks | 
| Efficacy trend: % predicted FEV1 | 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 | 104 weeks | 
| Efficacy trend: FEV1/FVC | FVC will be measured using a hand held spirometer, and will be recorded in Litres (L). Ratio of FEV1 and FVC will be reported. | 104 weeks | 
| Efficacy trend: Health services use | Number of non-study physician visits, emergency department (ED) and hospital admissions over the twelve-month study period. | 104 weeks | 
| Efficacy trend: Health care system cost | we will take the perspective of healthcare system and will measure the cost of health services use and an intervention. Intervention cost includes medication, staff, and equipment cost. | 104 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AECOPD, COPD