Hypogammaglobulinemia, Lung Transplantation
Conditions
Keywords
Hypogammaglobulinemia, Lung Transplantation
Brief summary
The purpose of this study is to determine if intravenous immunoglobulin (IVIG) can prevent bacterial infections in lung transplant patients with low serum levels of immunoglobulin.
Detailed description
An increased risk of infection despite intensive antimicrobial prophylaxis is a well-recognized complication of lung transplantation. Recent evidence suggests that immunosuppressive therapy after solid organ transplantation may lead to humoral immunodeficiency due to hypogammaglobulinemia (HGG). In lung transplant recipients with HGG, IVIG therapy offers the potential to significantly decrease the incidence and severity of infections, thereby reducing morbidity and potentially mortality. Comparison: The investigators are conducting a randomized clinical trial of IVIG versus placebo for lung transplant patients with severe HGG to see if IVIG decreases the number of bacterial infections in these patients.
Interventions
DRUGIVIG
10% Caprylate/Chromatography Purified Intravenous Immunoglobulin 400 mg/kg IV every 4 weeks
OTHERPlacebo
0.1% Albumin in an equal volume to the investigational product
Sponsors
Grifols Therapeutics LLC
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Lung transplant recipients \> 3 months after transplant surgery * Immunoglobulin G (IgG) \< 500 mg/dL * Stable medical regimen
Exclusion criteria
* Acute rejection * Active infection * Contraindication to IVIG * Pregnancy * Recent thrombotic event
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Clinically Diagnosed Bacterial Infections During the Treatment Period | 3 month | The number of events occurring during the treatment period. The data will be presented by the occurrence during the IVIG vs. the placebo treatment period, regardless of the order that the treatment was received. Only the clinically diagnosed bacterial infections will be counted. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Clinically Diagnosed Viral Infections | 3 month | This is to measure the effect of IVIG on viral infections. |
| Number of Hospital Admissions | 3 month | This is to measure the effect of IVIG on hospitalizations. |
| Number of Antibiotic Initiation | 3 month | This is to measure the effect of IVIG on the use of antibiotics. |
| Number of Clinically Diagnosed Fungal Infection | 3 months | This is to measure the effect of IVIG on fungal infections. |
| Number of Lymphocytic Bronchiolitis | 3 months | This is to measure the effect of IVIG on lung function. |
Countries
United States
Participant flow
Pre-assignment details
Eleven subjects were eligible and randomized, and 10 completed all study assessments. One subject discontinued the interventions because of inability to comply with the schedule of study visits. 10 subjects are needed to detect a reduction in the mean number of bacterial infections/patient by one standard deviation over three months with 80% power.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Study participants consented to receive three doses of IVIG (or 0.1% albumin solution (placebo)) given four weeks apart followed by a twelve-week washout and then three doses of placebo (or IVIG). | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 60 years |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 7 / 10 | 6 / 10 |
| serious Total, serious adverse events | 3 / 10 | 1 / 10 |
Outcome results
Primary
Number of Clinically Diagnosed Bacterial Infections During the Treatment Period
The number of events occurring during the treatment period. The data will be presented by the occurrence during the IVIG vs. the placebo treatment period, regardless of the order that the treatment was received. Only the clinically diagnosed bacterial infections will be counted.
Time frame: 3 month
Population: The crossover design, in which each subject serves as his or her own control, allows sufficient power for the detection of a clinically significant effect of IVIG with only a small number of patients. A sample size of 10 patients in a crossover trial has more power to detect differences than double the sample size using a parallel design.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving IVIG During Period 1 or Period 2 | Number of Clinically Diagnosed Bacterial Infections During the Treatment Period | 3 Infections |
| Participants Receiving Placebo During Period 1 or Period 2 | Number of Clinically Diagnosed Bacterial Infections During the Treatment Period | 1 Infections |
Secondary
Number of Antibiotic Initiation
This is to measure the effect of IVIG on the use of antibiotics.
Time frame: 3 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving IVIG During Period 1 or Period 2 | Number of Antibiotic Initiation | 9 Uses of antibiotics |
| Participants Receiving Placebo During Period 1 or Period 2 | Number of Antibiotic Initiation | 8 Uses of antibiotics |
Secondary
Number of Clinically Diagnosed Fungal Infection
This is to measure the effect of IVIG on fungal infections.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving IVIG During Period 1 or Period 2 | Number of Clinically Diagnosed Fungal Infection | 2 Infections |
| Participants Receiving Placebo During Period 1 or Period 2 | Number of Clinically Diagnosed Fungal Infection | 0 Infections |
Secondary
Number of Clinically Diagnosed Viral Infections
This is to measure the effect of IVIG on viral infections.
Time frame: 3 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving IVIG During Period 1 or Period 2 | Number of Clinically Diagnosed Viral Infections | 2 Number of Infections |
| Participants Receiving Placebo During Period 1 or Period 2 | Number of Clinically Diagnosed Viral Infections | 2 Number of Infections |
Secondary
Number of Hospital Admissions
This is to measure the effect of IVIG on hospitalizations.
Time frame: 3 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving IVIG During Period 1 or Period 2 | Number of Hospital Admissions | 3 Admissions |
| Participants Receiving Placebo During Period 1 or Period 2 | Number of Hospital Admissions | 1 Admissions |
Secondary
Number of Lymphocytic Bronchiolitis
This is to measure the effect of IVIG on lung function.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving IVIG During Period 1 or Period 2 | Number of Lymphocytic Bronchiolitis | 0 Instances of bronchiolitis |
| Participants Receiving Placebo During Period 1 or Period 2 | Number of Lymphocytic Bronchiolitis | 0 Instances of bronchiolitis |