Infections After Lung Transplant
Conditions
Brief summary
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
Interventions
DRUGSQ IVIG
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
Sponsors
CSL Behring
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Outcome Will be the Total Number of Days With Pneumonia. | Up to two years post-transplant | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Transplant Patients Who do Not Receive SQ IVIG Patients participating in the observational arm of the study who do not need to receive IgG replacement. | 122 |
| Transplant Patients Who Receive SQ IVIG Patients participating in the observational arm of the study who are randomized to receive a dosage of SQ IVIG due to low IgG level.
SQ IVIG: 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 | 11 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 13 | 0 |
Baseline characteristics
| Characteristic | Transplant Patients Who Receive SQ IVIG | Transplant Patients Who do Not Receive SQ IVIG | Total |
|---|---|---|---|
| Age, Continuous | 52 years | 62 years | 61 years |
| Diagnosis COPD | 3 Participants | 37 Participants | 40 Participants |
| Diagnosis Cystic Fibrosis | 3 Participants | 10 Participants | 13 Participants |
| Diagnosis IPF | 2 Participants | 44 Participants | 46 Participants |
| Diagnosis Other | 1 Participants | 14 Participants | 15 Participants |
| Diagnosis Pulmonary Hypertension | 0 Participants | 3 Participants | 3 Participants |
| Diagnosis Sarcoidosis | 1 Participants | 3 Participants | 4 Participants |
| Diagnosis Scleroderma | 1 Participants | 11 Participants | 12 Participants |
| Induction Agent Alemtuzamab | 5 Participants | 84 Participants | 89 Participants |
| Induction Agent Basiliximab | 6 Participants | 38 Participants | 44 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 8 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 113 Participants | 124 Participants |
| Sex: Female, Male Female | 5 Participants | 46 Participants | 51 Participants |
| Sex: Female, Male Male | 6 Participants | 76 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 13 / 122 | 0 / 11 |
| other Total, other adverse events | 0 / 122 | 0 / 11 |
| serious Total, serious adverse events | 0 / 122 | 0 / 11 |
Outcome results
Primary
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.
Time frame: Up to two years post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Transplant Patients Who do Not Receive SQ IVIG | The Primary Outcome Will be the Total Number of Days With Pneumonia. | 1714 Number of days |
| Transplant Patients Who Receive SQ IVIG | The Primary Outcome Will be the Total Number of Days With Pneumonia. | 51 Number of days |