Burkholderia Cepacia Infection, Cystic Fibrosis
Conditions
Keywords
inhaled antibiotics
Brief summary
The objective of this study is to determine if tobramycin inhalation powder (TIP) can reduce the amount of Burkholderia Cepacia Complex (BCC) species - type of bacteria, in the sputum of cystic fibrosis patient.
Interventions
DRUGTOBI
New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler
Sponsors
Unity Health Toronto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 6 years or older * Diagnosis of CF based on the following: sweat chloride\>60 mEq/L or genotype with 2 identifiable mutations consistent with CF; and one or more clinical features consistent with CF. * Chronically infected with a Burkholderia cepacia complex species (\>50% of respiratory specimens positive in the 24 months prior to screening). * Able to produce sputum (expectorated or induced). * Able to reproducibly perform pulmonary function testing. * Written informed consent provided.
Exclusion criteria
* Post lung transplantation. * Pregnancy. * Acute exacerbation requiring IV or oral antibiotics within 14 days * Patients currently receiving inhaled tobramycin/TOBI * A septic or clinically unstable patient, as determined by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change in Sputum Density of BCC in Colony Forming Units (CFUs)/ml From Day 0 to Day 28 of TIP Treatment. | 0 to 28 days | The change in sputum density of BCC in colony forming units (CFUs)/ml from day 0 to day 28 of TIP treatment. Sputum density was calculated by doing serial dilutions of sputum on agar plates and counting colony forming units expressed per ml. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Change in Pulmonary Function Tests, Including Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) and Maximal Mid-expiratory Flow Rate (FEF25-75), Measured at Day 0 and Day 28 of TIP Treatment. | 0 to 28 days | The main lung function measure was relative change in FEV1 from day 0 to Day 28 reported as %. |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Change in the Measurement of Markers of Pulmonary Inflammation (Neutrophil Counts, Neutrophil Elastase and IL-8 Levels in Sputum) Measured at Day 0 and Day 28 of TIP Treatment. | 0 to 28 days | We measured both neutrophil elastase sputum for participants. |
| Trough and Peak Sputum Tobramycin Concentration Measured on Day 28 of TIP Treatment. | Day 28 | We did trough (0 hour) and peak (1 hour post dose) TIP sputum tobramycin concentrations and reported it for participants. |
| The Change in BCC Planktonic and Biofilm MICs to Tobramycin Measured on Day 0 and on Day 28 of TIP Treatment. | 0 to 28 days | For all participants, the minimum inhibitory concentration of tobramycin for planktonic and biofilm grown BCC was measured in the lab on the isolate collected before and after TIP treatment. |
| The Number of Participants With Adverse Events Measured at Day 14 and at Day 28 of TIP Treatment. | At Dat 0, Day 14, and Day 28 | The number of participants with adverse events was reported for all participants in the trial. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TOBI Podhaler TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | TOBI Podhaler |
|---|---|
| Age, Categorical <=18 years | 4 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Burkholderia cenocepacia IIIA, n (%) | 4 Participants |
| Burkholderia cenocepacia IIIB, n (%) | 3 Participants |
| Burkholderia multivorans, n (%) | 3 Participants |
| Region of Enrollment Canada | 10 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 8 Participants |
| Sputum density log10 CFU/ml, median (range) | 7.9 log10 CFU/ml |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
The Change in Sputum Density of BCC in Colony Forming Units (CFUs)/ml From Day 0 to Day 28 of TIP Treatment.
The change in sputum density of BCC in colony forming units (CFUs)/ml from day 0 to day 28 of TIP treatment. Sputum density was calculated by doing serial dilutions of sputum on agar plates and counting colony forming units expressed per ml.
Time frame: 0 to 28 days
Population: sputum density measurements was calculated for all patients from Day 0 to Day 28
| Arm | Measure | Value (MEAN) |
|---|---|---|
| TOBI Podhaler | The Change in Sputum Density of BCC in Colony Forming Units (CFUs)/ml From Day 0 to Day 28 of TIP Treatment. | -1.4 CFU/ml log10 |
Secondary
The Change in Pulmonary Function Tests, Including Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) and Maximal Mid-expiratory Flow Rate (FEF25-75), Measured at Day 0 and Day 28 of TIP Treatment.
The main lung function measure was relative change in FEV1 from day 0 to Day 28 reported as %.
Time frame: 0 to 28 days
Population: All patients had lung function measures which were analyzed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| TOBI Podhaler | The Change in Pulmonary Function Tests, Including Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) and Maximal Mid-expiratory Flow Rate (FEF25-75), Measured at Day 0 and Day 28 of TIP Treatment. | 4.6 relative change in FEV1 expressed as % |
Other Pre-specified
The Change in BCC Planktonic and Biofilm MICs to Tobramycin Measured on Day 0 and on Day 28 of TIP Treatment.
For all participants, the minimum inhibitory concentration of tobramycin for planktonic and biofilm grown BCC was measured in the lab on the isolate collected before and after TIP treatment.
Time frame: 0 to 28 days
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| TOBI Podhaler | The Change in BCC Planktonic and Biofilm MICs to Tobramycin Measured on Day 0 and on Day 28 of TIP Treatment. | Day 0 | 200 ug/ml (MIC50) |
| TOBI Podhaler | The Change in BCC Planktonic and Biofilm MICs to Tobramycin Measured on Day 0 and on Day 28 of TIP Treatment. | Day 28 | 400 ug/ml (MIC50) |
Other Pre-specified
The Change in the Measurement of Markers of Pulmonary Inflammation (Neutrophil Counts, Neutrophil Elastase and IL-8 Levels in Sputum) Measured at Day 0 and Day 28 of TIP Treatment.
We measured both IL-8 sputum for participants.
Time frame: 0 to 28 days
Population: Sputum inflammatory markers were measured for 8 participants who could produce sputum.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| TOBI Podhaler | The Change in the Measurement of Markers of Pulmonary Inflammation (Neutrophil Counts, Neutrophil Elastase and IL-8 Levels in Sputum) Measured at Day 0 and Day 28 of TIP Treatment. | -127 IL-8 = ng/ml |
Other Pre-specified
The Change in the Measurement of Markers of Pulmonary Inflammation (Neutrophil Counts, Neutrophil Elastase and IL-8 Levels in Sputum) Measured at Day 0 and Day 28 of TIP Treatment.
We measured both neutrophil elastase sputum for participants.
Time frame: 0 to 28 days
Population: Sputum inflammatory markers were measured for 8 participants who could produce sputum.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| TOBI Podhaler | The Change in the Measurement of Markers of Pulmonary Inflammation (Neutrophil Counts, Neutrophil Elastase and IL-8 Levels in Sputum) Measured at Day 0 and Day 28 of TIP Treatment. | -51.9 NE = ug/ml |
Other Pre-specified
The Number of Participants With Adverse Events Measured at Day 14 and at Day 28 of TIP Treatment.
The number of participants with adverse events was reported for all participants in the trial.
Time frame: At Dat 0, Day 14, and Day 28
Population: We observed for adverse events in all participants and reported on those that had an adverse event.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TOBI Podhaler | The Number of Participants With Adverse Events Measured at Day 14 and at Day 28 of TIP Treatment. | 6 Participants |
Other Pre-specified
Trough and Peak Sputum Tobramycin Concentration Measured on Day 28 of TIP Treatment.
We did trough (0 hour) and peak (1 hour post dose) TIP sputum tobramycin concentrations and reported it for participants.
Time frame: Day 28
Population: We did pre and post TIP sputum tobramycin concentrations in 9 participants at Day 28 since one patient stopped taking the drug.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TOBI Podhaler | Trough and Peak Sputum Tobramycin Concentration Measured on Day 28 of TIP Treatment. | Trough (0 hr) | 194 ug/ml |
| TOBI Podhaler | Trough and Peak Sputum Tobramycin Concentration Measured on Day 28 of TIP Treatment. | Peak (1 hr post dose) | 1025 ug/ml |