COPD Exacerbation Acute
Conditions
Keywords
humoral dysfunction, humoral immune function
Brief summary
To examine the prevalence of humoral immunodeficiency in patients with Chronic Obstructive Pulmonary disease (COPD) by evaluating both immunoglobulin levels and vaccine responses. Patients with COPD and humoral dysfunction will be offered treatment with Subcutaneous Immune Globulin Replacement Therapy (SCIgR) in an attempt to decrease future AECOPD.
Detailed description
This will be a non-blinded, randomized study. Patients with COPD will be referred for evaluation by outpatient pulmonary clinics at Rochester Regional health. Following informed consent all patients will be evaluated by checking serum IgG, IgM, and IgA, as well as baseline and post-vaccine IgG to peptides antigens (diphtheria and tetanus) with Td as well as polysaccharide antigens (streptococcus pneumoniae) with pneumococcus polyvalent vaccine-23 (PPV23). Patients with COPD and pre-defined humoral dysfunction (please see below) will be randomized in 1:1 ratio to one of two groups until approximately 20 patients per group are accrued for a total of 40 patients Group #1: SCIgR with Cuvitru 125 mg/kg/week + standard of care management = 20 patients Group #2: Standard of care management = 20 patients
Interventions
BIOLOGICALCUVITRU - Ig subcutaneous human 20%
Subcutaneous Immunoglobin Replacement Therapy, SCigR
OTHERStandard Medical Therapy
Standard Medical Therapy
Sponsors
Takeda
Rochester General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
non-blinded, randomized study. Patients with COPD will be referred for evaluation by outpatient pulmonary clinics at Rochester Regional health. Following informed consent all patients will be evaluated by checking serum IgG, IgM, and IgA, as well as baseline and post-vaccine IgG to peptides antigens (diphtheria and tetanus) with Td as well as polysaccharide antigens (streptococcus pneumoniae) with pneumococcus polyvalent vaccine-23 (PPV23). Patients with COPD and pre-defined humoral dysfunction (please see below) will be randomized in 1:1 ratio to one of two groups until approximately 20 patients per group are accrued for a total of 40 patients
Eligibility
Sex/Gender
ALL
Age
18 Years to 82 Years
Healthy volunteers
No
Inclusion criteria
1. Patients \> 18 years and ≤ 82 years old. 2. Patient that meet three (3) or more of the five (5) following criteria. 1. Dyspnea ≥ 5 on a visual analog scale 2. Respiratory rate ≥ 24 breaths per minute 3. Heart rate ≥ 95 beats per minute 4. Resting SaO2 \< 92% breathing ambient air of the patient's usual oxygen prescription and/or change in saturation \> 3% from baseline 5. CRP ≥ 10 mg/L 3. Established diagnosis of COPD with PFTs showing FEV1/FVC \< 70% or FEV1/VC ratio below the 5th percentile of the predicted value.\[14\] 4. Subjects must have adherence with triple therapy \[Inhaled Corticosteroid (ICS), Long-acting beta2-adrenergic agonist (LABA), Long-acting muscarinic antagonist (LAMA)\] for greater than 90 Days prior to consideration of participation in this study. 5. With triple therapy onboard, the subject must have ≥ 2 steroid-requiring exacerbations (defined by increased respiratory symptoms of increased cough, dyspnea, sputum, sputum purulence, wheeze, chest tightness) requiring treatment with systemic steroids within the past 12 months OR one exacerbation requiring inpatient hospitalization 6. Medically stable with no acute hospitalizations for non-COPD related events within the last 3 months 7. Expected life expectancy \> 1 year 8. Stable Cardiovascular Disease, with no planned intervention 9. No history of pulmonary embolism or embolic event 10. Hepatic function \< Class B Child-Pugh criteria 11. Renal insufficiency with eGFR \> 60 mL/min/1.73m2 12. No history of DVT or thrombotic events 13. No history of prior organ transplant 14. Female subjects of childbearing potential will need to have a negative pregnancy test performed within 14 days prior to study procedure (if applicable) and be adherent to an accepted method of contraception. 15. Male subject will need to adhere to barrier contraception during the course of the trial and for 1 month after completion of the final injection of Cuvitru. 16. Ability to sign informed consent
Exclusion criteria
1. Known history of humoral dysfunction/immunodeficiency 2. Known hereditary/genetic/congenital defects, and autoimmune disease including hereditary spherocytosis, hereditary elliptocytosis, paroxysmal nocturnal hemoglobinuria, and sickle cell disease 3. Ongoing or recent therapy with immunoglobulin replacement therapy within the past 6 months 4. Chronic oral steroid use of prednisone treatment of ≥20 mg daily (or equivalent) will be excluded to ensure subject is medically stable. 5. Alpha-1 antitrypsin deficiency 6. Obesity with a BMI \> 40 7. Unstable hypertension systolic blood pressure (SBP) \>160 mmHg upon repeated measure 8. Diabetes mellitus Type I 9. Known history of acquired or inherited thrombophilia disorders 10. Known risk factors of hemolysis, including G6PD deficiency, mitral valve replacement, aortic valve replacement. 11. Known prolonged periods of immobilization 12. Known severe hypovolemia noted by SBP ≤ 85 and/or heart rate (HR) \>130 13. Known hypercoagulable conditions 14. Use of estrogens 15. Indwelling central vascular catheters 16. Currently actively smoking
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AECOPD requiring treatment with systemic steroids over one year | one year | AECOPD is defined by increased respiratory symptoms (e.g., cough, dyspnea, sputum, sputum purulence, wheeze, chest tightness) requiring treatment with systemic steroids. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| COPD with pre-defined humoral dysfunction treated with subcutaneous SCIgR will have decreased AECOPD events as compared to COPD with pre-defined humoral dysfunction treated with the standard of care (SOC) management. | one year | AECOPD events will be determined by evaluating the rate of re-hospitalization in both treatment groups (ie with subcutaneous SCIgR + SOC versus SOC). The treatment group with subcutaneous SCIgR + SOC will have decreased AECOPD events as evidenced by the lower rehospitalization rate in comparison to the SOC treatment group's rehospitalization rate. |
Countries
United States
Contacts
Primary ContactDawn Sheflin, RN
Backup ContactHolly Blue, LPN
Outcome results
None listed