Immunoglobulin Levels and Occurrence of Infections After Lung Transplantation and Impact of IgG Replacement

Study Overview
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Brief Summary
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Immunosuppressive therapies have led to remarkable improvements in survival in lung transplantation (LT) patients. However, one important adverse effect of these therapies has been the increasing emergence of hypogammaglobulinemia (HGG) which has been previously seen mostly in patients with primary immunodeficiency (PID). The goal of treatment of HGG in PID has been to maintain the trough IgG level above 500 mg/dl which might provide better protection against infections than do lower IgG serum concentrations. Although IgG therapy is of substantial benefit, the doses and trough levels of IgG that are optimal are not yet clearly established. The impact of high versus low IgG dosing on the frequency and severity of infections and rejection has not been studied before in LT patients with HGG. The specific aims for this study are to compare the incidence of infections in lung transplant recipients receiving higher versus lower dose of SQ IgG and to compare the incidence of infections in lung transplant recipients with mild hypogammaglobulinemia versus normal IgG levels. This study will be a single center study of all lung transplant recipients, age 18 years or older, at the University of Pittsburgh Medical Center (UPMC), with a randomized treatment arm and an observational arm. The hypotheses for the research study are: Therapy with IV or SQ IgG is of substantial benefit in reducing the number of infections in lung transplant recipients with severe hypogammaglobulinemia (IgG < 500) A higher dose of SQ IgG, with subsequent higher trough IgG levels, may have a higher impact on the frequency and severity of infections and rejection episodes, compared to a lower dose of SQ IgG, with subsequent lower IgG trough levels Lung transplant recipients with mild hypogammaglobulinemia ( IgG= 500-750) have a higher incidence of infections compared to patients with normal IgG levels

Official Title
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Immunoglobulin Levels and Occurrence of Infections After Lung Transplantation and Impact of IgG Replacement - Observational Arm

Conditions
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Infections After Lung Transplant

Intervention / Treatment
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* Drug: SQ IVIG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult recipients of lung transplantation at the University of Pittsburgh Medical Center, who are able to provide written informed consent prior to transplantation or on the day of lung transplant surgery. Exclusion Criteria: age less than 18 years-old history of anaphylaxis to IVIG subjects already on IV or SQ IgG treatment

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Transplant patients who do not receive SQ IVIG<br>Patients participating in the observational arm of the study who do not need to receive IgG replacement. | |
| Active Comparator: Transplant patients who receive SQ IVIG<br>Patients participating in the observational arm of the study who are randomized to receive a dosage of SQ IVIG due to low IgG level. | Drug: SQ IVIG<br>* Group 1 will receive SQ IgG at the lower end of the dosing range at 100 mg/kg/week and group 2 will receive SQ IgG at the higher end of the dosing range at 200 mg/kg/week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Outcome Will be the Total Number of Days With Pneumonia. | The primary outcome for this study will be the total number of days with pneumonia. Pneumonia will be defined by the presence of both clinical and radiographic criteria: fever (temperature ≥ 38oC), cough, dyspnea, purulent expectoration and/or changes in the previous characteristics of respiratory secretions; and chest X-ray or CT scan revealing a new or progressive alveolar or interstitial infiltrate or cavitation that could not be explained by any other noninfectious cause. | Up to two years post-transplant |