Prevalence of Humoral Immune Deficiency in Patients With Frequent Exacerbations of COPD, and the Effect of Immunoglobulin Replacement on Future Exacerbations
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 3
- 主要终点
- AECOPD requiring treatment with systemic steroids over one year
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 82 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients > 18 years and ≤ 82 years old.
- •Patient that meet three (3) or more of the five (5) following criteria.
- •Dyspnea ≥ 5 on a visual analog scale
- •Respiratory rate ≥ 24 breaths per minute
- •Heart rate ≥ 95 beats per minute
- •Resting SaO2 < 92% breathing ambient air of the patient's usual oxygen prescription and/or change in saturation > 3% from baseline
- •CRP ≥ 10 mg/L
- •Established diagnosis of COPD with PFTs showing FEV1/FVC < 70% or FEV1/VC ratio below the 5th percentile of the predicted value.[14]
- •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.
- •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
- •Medically stable with no acute hospitalizations for non-COPD related events within the last 3 months
- •Expected life expectancy > 1 year
- •Stable Cardiovascular Disease, with no planned intervention
- •No history of pulmonary embolism or embolic event
- •Hepatic function < Class B Child-Pugh criteria
- •Renal insufficiency with eGFR > 60 mL/min/1.73m2
- •No history of DVT or thrombotic events
- •No history of prior organ transplant
- •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.
- •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.
- •Ability to sign informed consent
排除标准
- •Known history of humoral dysfunction/immunodeficiency
- •Known hereditary/genetic/congenital defects, and autoimmune disease including hereditary spherocytosis, hereditary elliptocytosis, paroxysmal nocturnal hemoglobinuria, and sickle cell disease
- •Ongoing or recent therapy with immunoglobulin replacement therapy within the past 6 months
- •Chronic oral steroid use of prednisone treatment of ≥20 mg daily (or equivalent) will be excluded to ensure subject is medically stable.
- •Alpha-1 antitrypsin deficiency
- •Obesity with a BMI > 40
- •Unstable hypertension systolic blood pressure (SBP) >160 mmHg upon repeated measure
- •Diabetes mellitus Type I
- •Known history of acquired or inherited thrombophilia disorders
- •Known risk factors of hemolysis, including G6PD deficiency, mitral valve replacement, aortic valve replacement.
- •Known prolonged periods of immobilization
- •Known severe hypovolemia noted by SBP ≤ 85 and/or heart rate (HR) >130
- •Known hypercoagulable conditions
- •Use of estrogens
- •Indwelling central vascular catheters
- •Currently actively smoking
研究组 & 干预措施
Group #1
SCIgR with Cuvitru 125 mg/kg/week + standard of care management
干预措施: CUVITRU - Ig subcutaneous human 20% (Biological)
Group #1
SCIgR with Cuvitru 125 mg/kg/week + standard of care management
干预措施: Standard Medical Therapy (Other)
Group #2
Standard of care management = 20 patients
干预措施: Standard Medical Therapy (Other)
结局指标
主要结局
AECOPD requiring treatment with systemic steroids over one year
时间窗: one year
AECOPD is defined by increased respiratory symptoms (e.g., cough, dyspnea, sputum, sputum purulence, wheeze, chest tightness) requiring treatment with systemic steroids.
次要结局
- 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)
研究者
S. Shahzad Mustafa
Principle Investigator
Rochester General Hospital