Treatment of Early Pulmonary Infections With P. Aeruginosa in Cystic Fibrosis Patients
Conditions
Keywords
Tobramycin Inhalation solution, Cystic fibrosis, Lung disease, anti-bacterial agents
Brief summary
This study investigated the efficacy of inhaled TOBI treatment for early infections of P. aeruginosa in paediatric patients with cystic fibrosis.
Interventions
DRUGTOBI
TOBI (tobramycin inhaled solution)
DRUGPlacebo
Placebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Months to 6 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of cystic fibrosis * Early lower respiratory tract infection with P. aeruginosa,
Exclusion criteria
* Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics. * Administration of loop diuretics within 7 days prior to study drug administration. * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants P Aeruginosa-free After Completion of the First Treatment Cycle | Day 29 | Sputum/throat swab cultures were assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Free From P. Aeruginosa 28 Days After Termination of the Second Treatment Cycle | Day 91 | Sputum/throat swab cultures were assessed. |
| Percentage of Participants P Aeruginosa-free at Termination of the Double Blind Period | Day 91 | Sputum/throat swab cultures were assessed. |
Countries
Canada, Egypt, France, Germany, Greece, Hungary, Italy, Romania, Russia, Switzerland
Participant flow
Recruitment details
Participants were randomized 1:1 to TOBI or placebo. After 1 treatment cycle, participants who were P.a positive entered an OL phase. Participants who were P.a negative entered cross-over treatment.
Pre-assignment details
The cross-over was optional. At the end of the cross-over or OL phase, participants who were P.a positive terminated the study. P.a negative participants entered follow-up.
Participants by arm
| Arm | Count |
|---|---|
| TOBI (Tobramycin Inhaled Solution)/Placebo Participants randomized to TOBI received the investigational treatment for 28 days twice daily (bi)d in the first treatment cycle. At the end of first treatment cycle, participants who were positive for P. aeruginosa entered the open label (OL) phase of the study and received TOBI for 28 days bid. Participants who were negative for P. aeruginosa at the end of first treatment cycle and agreed to participate in the cross-over treatment period received placebo for 28 days bid (second treatment cycle). Eligible participants were followed-up for up to 12-months, having visits every 3 months. If participants were detected P. aeruginosa positive, they received 28-days of OL TOBI. Participants who remained P.aeruginosa positive after TOBI OL treatment discontinued the study. Participants who became P.aeruginosa negative after OL TOBI treatment remained in the study. | 26 |
| Placebo/TOBI Participants randomized to placebo group received 0.9 % saline (NaCl) for 28 days bid in the first treatment cycle. At the end of first treatment cycle, participants who were positive for P. aeruginosa entered the OL phase of the study and received TOBI for 28 days bid. Participants who were negative for P. aeruginosa at the end of first treatment cycle and agreed to participate in the cross-over treatment period received TOBI for 28 days bid (second treatment cycle). Eligible participants were followed-up for up to 12-months, having visits every 3 months. If participants were detected P. aeruginosa positive, they received 28-days of OL TOBI. Participants who remained P.aeruginosa positive after TOBI OL treatment discontinued the study. Participants who became P.aeruginosa negative after OL TOBI treatment remained in the study. | 25 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Period | Administrative problems | 0 | 1 |
| Double-blind Period | Adverse Event | 0 | 1 |
| Double-blind Period | Lack of Efficacy | 5 | 11 |
| Follow-up (F-U) Period | Abnormal lab values | 1 | 0 |
| Follow-up (F-U) Period | Administrative problems | 1 | 0 |
| Follow-up (F-U) Period | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | TOBI (Tobramycin Inhaled Solution)/Placebo | Placebo/TOBI | Total |
|---|---|---|---|
| Age, Continuous | 2.9 Years STANDARD_DEVIATION 1.96 | 2.7 Years STANDARD_DEVIATION 1.93 | 2.8 Years STANDARD_DEVIATION 1.93 |
| Sex: Female, Male Female | 15 Participants | 17 Participants | 32 Participants |
| Sex: Female, Male Male | 11 Participants | 8 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 32 | 18 / 38 | 10 / 22 | 13 / 50 | 2 / 10 | 23 / 29 |
| serious Total, serious adverse events | 0 / 32 | 1 / 38 | 0 / 22 | 2 / 50 | 0 / 10 | 4 / 29 |
Outcome results
Primary
Percentage of Participants P Aeruginosa-free After Completion of the First Treatment Cycle
Sputum/throat swab cultures were assessed.
Time frame: Day 29
Population: Intent-to-treat (ITT): The ITT included all randomized participants who received at least dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TOBI (Tobramycin Inhaled Solution)/Placebo | Percentage of Participants P Aeruginosa-free After Completion of the First Treatment Cycle | 84.6 Percentage of participants |
| Placebo/TOBI | Percentage of Participants P Aeruginosa-free After Completion of the First Treatment Cycle | 24.0 Percentage of participants |
p-value: <0.00195% CI: [4.67, 99.52]Regression, Logistic
Secondary
Percentage of Participants Free From P. Aeruginosa 28 Days After Termination of the Second Treatment Cycle
Sputum/throat swab cultures were assessed.
Time frame: Day 91
Population: Cross-over participants from the ITT population were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TOBI (Tobramycin Inhaled Solution)/Placebo | Percentage of Participants Free From P. Aeruginosa 28 Days After Termination of the Second Treatment Cycle | 92.3 Percentage of participants |
| Placebo/TOBI | Percentage of Participants Free From P. Aeruginosa 28 Days After Termination of the Second Treatment Cycle | 83.3 Percentage of participants |
Secondary
Percentage of Participants P Aeruginosa-free at Termination of the Double Blind Period
Sputum/throat swab cultures were assessed.
Time frame: Day 91
Population: Participants from the ITT population, who were tested for microbiology, were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TOBI (Tobramycin Inhaled Solution)/Placebo | Percentage of Participants P Aeruginosa-free at Termination of the Double Blind Period | 76.0 Percentage of participants |
| Placebo/TOBI | Percentage of Participants P Aeruginosa-free at Termination of the Double Blind Period | 47.8 Percentage of participants |