Trial Outcomes & Findings for Inhaled Tobramycin in BPD (NCT NCT04560179)
NCT ID: NCT04560179
Last Updated: 2025-01-31
Results Overview
Trough serum tobramycin level (measured 11 hours after the administered dose) ≥1mcg/mL; increase in serum creatinine level by ≥0.3mg/dL above pre-trial baseline; increase in serum creatinine level \>1.5-fold above pre-trial baseline; urine output \<0.5mL/kg/hr for 12 consecutive hours; or any serious adverse event possibly attributable to the study drug
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
27 participants
Primary outcome timeframe
Any time during the 14-day trial
Results posted on
2025-01-31
Participant Flow
A total of 27 infants were enrolled into the study protocol and underwent collection of a screening tracheal aspirate culture to determine eligibility for the entry into the phase 1 drug trial. Of these 27, 16 (59%) infants had a tracheal aspirate culture positive for an eligible Gram-negative pathogen. OF these 16, all were enrolled into the phase 1 drug trial. No parents/guardians elected to enroll their child in the untreated observational arm prior to completion of all dose levels.
Participant milestones
| Measure |
Treatment Arm - 78mg
The phase 1 trial will begin with a dose of 78mg. All treatment arms will administer study drug every 12 hours for up to 14 days (28 doses). Up to 6 infants in this arm will receive the 78mg dose of tobramycin solution for inhalation administered via vibrating mesh nebulizer. During the trial, infants in each treatment arm will undergo blood and tracheal aspirate sampling and respiratory mechanics measurements at pre-specified time points to assess dose safety and potential efficacy. Continuous pulse oximetry monitoring for the duration of the trial will also occur. Clinical data will also be recorded daily throughout the trial in all participants.
Tobramycin solution for inhalation 78mg dose: Inhaled tobramycin - 78mg administered every 12 hours for 14 days.
|
Treatment Arm - 150mg
If tolerability is demonstrated in the 78mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 150mg dose: Inhaled tobramycin - 150mg administered every 12 hours for 14 days.
|
Treatment Arm - 216mg
If tolerability is demonstrated in the 150mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 216mg dose: Inhaled tobramycin - 216mg administered every 12 hours for 14 days.
|
Treatment Arm - 300mg
If tolerability is demonstrated in the 216mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 300mg dose: Inhaled tobramycin - 300mg administered every 12 hours for 14 days.
|
Observational Arm
Enrolled infants who are eligible to participate in the phase-1 trial may be enrolled in an untreated observational cohort at parental discretion. This cohort will undergo collection of clinical and respiratory mechanics data for 14 days after enrollment but will not receive the study drug.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
3
|
3
|
6
|
0
|
|
Overall Study
COMPLETED
|
3
|
3
|
3
|
5
|
0
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Treatment Arm - 78mg
The phase 1 trial will begin with a dose of 78mg. All treatment arms will administer study drug every 12 hours for up to 14 days (28 doses). Up to 6 infants in this arm will receive the 78mg dose of tobramycin solution for inhalation administered via vibrating mesh nebulizer. During the trial, infants in each treatment arm will undergo blood and tracheal aspirate sampling and respiratory mechanics measurements at pre-specified time points to assess dose safety and potential efficacy. Continuous pulse oximetry monitoring for the duration of the trial will also occur. Clinical data will also be recorded daily throughout the trial in all participants.
Tobramycin solution for inhalation 78mg dose: Inhaled tobramycin - 78mg administered every 12 hours for 14 days.
|
Treatment Arm - 150mg
If tolerability is demonstrated in the 78mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 150mg dose: Inhaled tobramycin - 150mg administered every 12 hours for 14 days.
|
Treatment Arm - 216mg
If tolerability is demonstrated in the 150mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 216mg dose: Inhaled tobramycin - 216mg administered every 12 hours for 14 days.
|
Treatment Arm - 300mg
If tolerability is demonstrated in the 216mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 300mg dose: Inhaled tobramycin - 300mg administered every 12 hours for 14 days.
|
Observational Arm
Enrolled infants who are eligible to participate in the phase-1 trial may be enrolled in an untreated observational cohort at parental discretion. This cohort will undergo collection of clinical and respiratory mechanics data for 14 days after enrollment but will not receive the study drug.
|
|---|---|---|---|---|---|
|
Overall Study
Physician Decision
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Inhaled Tobramycin in BPD
Baseline characteristics by cohort
| Measure |
Treatment Arm - 78mg
n=4 Participants
The phase 1 trial will begin with a dose of 78mg. All treatment arms will administer study drug every 12 hours for up to 14 days (28 doses). Up to 6 infants in this arm will receive the 78mg dose of tobramycin solution for inhalation administered via vibrating mesh nebulizer. During the trial, infants in each treatment arm will undergo blood and tracheal aspirate sampling and respiratory mechanics measurements at pre-specified time points to assess dose safety and potential efficacy. Continuous pulse oximetry monitoring for the duration of the trial will also occur. Clinical data will also be recorded daily throughout the trial in all participants.
Tobramycin solution for inhalation 78mg dose: Inhaled tobramycin - 78mg administered every 12 hours for 14 days.
|
Treatment Arm - 150mg
n=3 Participants
If tolerability is demonstrated in the 78mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 150mg dose: Inhaled tobramycin - 150mg administered every 12 hours for 14 days.
|
Treatment Arm - 216mg
n=3 Participants
If tolerability is demonstrated in the 150mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 216mg dose: Inhaled tobramycin - 216mg administered every 12 hours for 14 days.
|
Treatment Arm - 300mg
n=6 Participants
If tolerability is demonstrated in the 216mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 300mg dose: Inhaled tobramycin - 300mg administered every 12 hours for 14 days.
|
Observational Arm
Enrolled infants who are eligible to participate in the phase-1 trial may be enrolled in an untreated observational cohort at parental discretion. This cohort will undergo collection of clinical and respiratory mechanics data for 14 days after enrollment but will not receive the study drug.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
16 Participants
n=8 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
7 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
9 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
12 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
11 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
6 participants
n=4 Participants
|
—
|
16 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Any time during the 14-day trialPopulation: No infants were enrolled into the observational arm. 1 of the 16 enrolled infants (treatment arm - 78mg) was withdrawn early from the trial by the medical team and was not assessed for this outcome.
Trough serum tobramycin level (measured 11 hours after the administered dose) ≥1mcg/mL; increase in serum creatinine level by ≥0.3mg/dL above pre-trial baseline; increase in serum creatinine level \>1.5-fold above pre-trial baseline; urine output \<0.5mL/kg/hr for 12 consecutive hours; or any serious adverse event possibly attributable to the study drug
Outcome measures
| Measure |
Treatment Arm - 78mg
n=3 Participants
The phase 1 trial will begin with a dose of 78mg. All treatment arms will administer study drug every 12 hours for up to 14 days (28 doses). Up to 6 infants in this arm will receive the 78mg dose of tobramycin solution for inhalation administered via vibrating mesh nebulizer. During the trial, infants in each treatment arm will undergo blood and tracheal aspirate sampling and respiratory mechanics measurements at pre-specified time points to assess dose safety and potential efficacy. Continuous pulse oximetry monitoring for the duration of the trial will also occur. Clinical data will also be recorded daily throughout the trial in all participants.
Tobramycin solution for inhalation 78mg dose: Inhaled tobramycin - 78mg administered every 12 hours for 14 days.
|
Treatment Arm - 150mg
n=3 Participants
If tolerability is demonstrated in the 78mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 150mg dose: Inhaled tobramycin - 150mg administered every 12 hours for 14 days.
|
Treatment Arm - 216mg
n=3 Participants
If tolerability is demonstrated in the 150mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 216mg dose: Inhaled tobramycin - 216mg administered every 12 hours for 14 days.
|
Treatment Arm - 300mg
n=6 Participants
If tolerability is demonstrated in the 216mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 300mg dose: Inhaled tobramycin - 300mg administered every 12 hours for 14 days.
|
Observational Arm
Enrolled infants who are eligible to participate in the phase-1 trial may be enrolled in an untreated observational cohort at parental discretion. This cohort will undergo collection of clinical and respiratory mechanics data for 14 days after enrollment but will not receive the study drug.
|
Screened But Not Eligible
Enrolled infants who did not have evidence of a Gram-negative bacteria present on a prospective tracheal aspirate culture obtained for this trial and thus were not eligible to receive study drug.
|
|---|---|---|---|---|---|---|
|
Elevated Serum Tobramycin Trough or Creatinine or Severe Adverse Event
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Any time during the 14-day trialPopulation: No infants were enrolled into the observational arm. 1 of the 16 enrolled infants (treatment arm - 78mg) was withdrawn early from the trial by the medical team and was not assessed for this outcome.
Outcome measures
| Measure |
Treatment Arm - 78mg
n=3 Participants
The phase 1 trial will begin with a dose of 78mg. All treatment arms will administer study drug every 12 hours for up to 14 days (28 doses). Up to 6 infants in this arm will receive the 78mg dose of tobramycin solution for inhalation administered via vibrating mesh nebulizer. During the trial, infants in each treatment arm will undergo blood and tracheal aspirate sampling and respiratory mechanics measurements at pre-specified time points to assess dose safety and potential efficacy. Continuous pulse oximetry monitoring for the duration of the trial will also occur. Clinical data will also be recorded daily throughout the trial in all participants.
Tobramycin solution for inhalation 78mg dose: Inhaled tobramycin - 78mg administered every 12 hours for 14 days.
|
Treatment Arm - 150mg
n=3 Participants
If tolerability is demonstrated in the 78mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 150mg dose: Inhaled tobramycin - 150mg administered every 12 hours for 14 days.
|
Treatment Arm - 216mg
n=3 Participants
If tolerability is demonstrated in the 150mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 216mg dose: Inhaled tobramycin - 216mg administered every 12 hours for 14 days.
|
Treatment Arm - 300mg
n=6 Participants
If tolerability is demonstrated in the 216mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 300mg dose: Inhaled tobramycin - 300mg administered every 12 hours for 14 days.
|
Observational Arm
Enrolled infants who are eligible to participate in the phase-1 trial may be enrolled in an untreated observational cohort at parental discretion. This cohort will undergo collection of clinical and respiratory mechanics data for 14 days after enrollment but will not receive the study drug.
|
Screened But Not Eligible
Enrolled infants who did not have evidence of a Gram-negative bacteria present on a prospective tracheal aspirate culture obtained for this trial and thus were not eligible to receive study drug.
|
|---|---|---|---|---|---|---|
|
New Onset or Worsened Coughing Associated With a Change in Respiratory Status (SpO2 <80% for >10 Seconds; Need for Increase in FiO2 by >20%)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Any time during the 14-day trialPopulation: No infants were enrolled into the observational arm. 1 of the 16 enrolled infants (treatment arm - 78mg) was withdrawn early from the trial by the medical team and was not assessed for this outcome.
Outcome measures
| Measure |
Treatment Arm - 78mg
n=3 Participants
The phase 1 trial will begin with a dose of 78mg. All treatment arms will administer study drug every 12 hours for up to 14 days (28 doses). Up to 6 infants in this arm will receive the 78mg dose of tobramycin solution for inhalation administered via vibrating mesh nebulizer. During the trial, infants in each treatment arm will undergo blood and tracheal aspirate sampling and respiratory mechanics measurements at pre-specified time points to assess dose safety and potential efficacy. Continuous pulse oximetry monitoring for the duration of the trial will also occur. Clinical data will also be recorded daily throughout the trial in all participants.
Tobramycin solution for inhalation 78mg dose: Inhaled tobramycin - 78mg administered every 12 hours for 14 days.
|
Treatment Arm - 150mg
n=3 Participants
If tolerability is demonstrated in the 78mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 150mg dose: Inhaled tobramycin - 150mg administered every 12 hours for 14 days.
|
Treatment Arm - 216mg
n=3 Participants
If tolerability is demonstrated in the 150mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 216mg dose: Inhaled tobramycin - 216mg administered every 12 hours for 14 days.
|
Treatment Arm - 300mg
n=6 Participants
If tolerability is demonstrated in the 216mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 300mg dose: Inhaled tobramycin - 300mg administered every 12 hours for 14 days.
|
Observational Arm
Enrolled infants who are eligible to participate in the phase-1 trial may be enrolled in an untreated observational cohort at parental discretion. This cohort will undergo collection of clinical and respiratory mechanics data for 14 days after enrollment but will not receive the study drug.
|
Screened But Not Eligible
Enrolled infants who did not have evidence of a Gram-negative bacteria present on a prospective tracheal aspirate culture obtained for this trial and thus were not eligible to receive study drug.
|
|---|---|---|---|---|---|---|
|
Obstruction of the Endotracheal Tube Requiring Tube Replacement
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Any time during the 14-day trialPopulation: No infants were enrolled into the observational arm. 1 of the 16 enrolled infants (treatment arm - 78mg) was withdrawn early from the trial by the medical team and was not assessed for this outcome.
Outcome measures
| Measure |
Treatment Arm - 78mg
n=3 Participants
The phase 1 trial will begin with a dose of 78mg. All treatment arms will administer study drug every 12 hours for up to 14 days (28 doses). Up to 6 infants in this arm will receive the 78mg dose of tobramycin solution for inhalation administered via vibrating mesh nebulizer. During the trial, infants in each treatment arm will undergo blood and tracheal aspirate sampling and respiratory mechanics measurements at pre-specified time points to assess dose safety and potential efficacy. Continuous pulse oximetry monitoring for the duration of the trial will also occur. Clinical data will also be recorded daily throughout the trial in all participants.
Tobramycin solution for inhalation 78mg dose: Inhaled tobramycin - 78mg administered every 12 hours for 14 days.
|
Treatment Arm - 150mg
n=3 Participants
If tolerability is demonstrated in the 78mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 150mg dose: Inhaled tobramycin - 150mg administered every 12 hours for 14 days.
|
Treatment Arm - 216mg
n=3 Participants
If tolerability is demonstrated in the 150mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 216mg dose: Inhaled tobramycin - 216mg administered every 12 hours for 14 days.
|
Treatment Arm - 300mg
n=6 Participants
If tolerability is demonstrated in the 216mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 300mg dose: Inhaled tobramycin - 300mg administered every 12 hours for 14 days.
|
Observational Arm
Enrolled infants who are eligible to participate in the phase-1 trial may be enrolled in an untreated observational cohort at parental discretion. This cohort will undergo collection of clinical and respiratory mechanics data for 14 days after enrollment but will not receive the study drug.
|
Screened But Not Eligible
Enrolled infants who did not have evidence of a Gram-negative bacteria present on a prospective tracheal aspirate culture obtained for this trial and thus were not eligible to receive study drug.
|
|---|---|---|---|---|---|---|
|
Unplanned Tracheal Extubation
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Any time during the 14 day trialPopulation: No infants were enrolled into the observational arm. Infants who were screened but not eligible did not receive study drug.
Outcome measures
| Measure |
Treatment Arm - 78mg
n=3 Participants
The phase 1 trial will begin with a dose of 78mg. All treatment arms will administer study drug every 12 hours for up to 14 days (28 doses). Up to 6 infants in this arm will receive the 78mg dose of tobramycin solution for inhalation administered via vibrating mesh nebulizer. During the trial, infants in each treatment arm will undergo blood and tracheal aspirate sampling and respiratory mechanics measurements at pre-specified time points to assess dose safety and potential efficacy. Continuous pulse oximetry monitoring for the duration of the trial will also occur. Clinical data will also be recorded daily throughout the trial in all participants.
Tobramycin solution for inhalation 78mg dose: Inhaled tobramycin - 78mg administered every 12 hours for 14 days.
|
Treatment Arm - 150mg
n=3 Participants
If tolerability is demonstrated in the 78mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 150mg dose: Inhaled tobramycin - 150mg administered every 12 hours for 14 days.
|
Treatment Arm - 216mg
n=3 Participants
If tolerability is demonstrated in the 150mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 216mg dose: Inhaled tobramycin - 216mg administered every 12 hours for 14 days.
|
Treatment Arm - 300mg
n=6 Participants
If tolerability is demonstrated in the 216mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 300mg dose: Inhaled tobramycin - 300mg administered every 12 hours for 14 days.
|
Observational Arm
Enrolled infants who are eligible to participate in the phase-1 trial may be enrolled in an untreated observational cohort at parental discretion. This cohort will undergo collection of clinical and respiratory mechanics data for 14 days after enrollment but will not receive the study drug.
|
Screened But Not Eligible
Enrolled infants who did not have evidence of a Gram-negative bacteria present on a prospective tracheal aspirate culture obtained for this trial and thus were not eligible to receive study drug.
|
|---|---|---|---|---|---|---|
|
Desaturation (SpO2 <80% for >10 Seconds) During Administration of Inhaled Tobramycin
|
3 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: up to 1 year of agePopulation: 14 of the 16 phase 1 trial participants were assessed for failed audiology examination. The remaining two died prior to testing.
Outcome measures
| Measure |
Treatment Arm - 78mg
n=3 Participants
The phase 1 trial will begin with a dose of 78mg. All treatment arms will administer study drug every 12 hours for up to 14 days (28 doses). Up to 6 infants in this arm will receive the 78mg dose of tobramycin solution for inhalation administered via vibrating mesh nebulizer. During the trial, infants in each treatment arm will undergo blood and tracheal aspirate sampling and respiratory mechanics measurements at pre-specified time points to assess dose safety and potential efficacy. Continuous pulse oximetry monitoring for the duration of the trial will also occur. Clinical data will also be recorded daily throughout the trial in all participants.
Tobramycin solution for inhalation 78mg dose: Inhaled tobramycin - 78mg administered every 12 hours for 14 days.
|
Treatment Arm - 150mg
n=3 Participants
If tolerability is demonstrated in the 78mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 150mg dose: Inhaled tobramycin - 150mg administered every 12 hours for 14 days.
|
Treatment Arm - 216mg
n=3 Participants
If tolerability is demonstrated in the 150mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 216mg dose: Inhaled tobramycin - 216mg administered every 12 hours for 14 days.
|
Treatment Arm - 300mg
n=5 Participants
If tolerability is demonstrated in the 216mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 300mg dose: Inhaled tobramycin - 300mg administered every 12 hours for 14 days.
|
Observational Arm
Enrolled infants who are eligible to participate in the phase-1 trial may be enrolled in an untreated observational cohort at parental discretion. This cohort will undergo collection of clinical and respiratory mechanics data for 14 days after enrollment but will not receive the study drug.
|
Screened But Not Eligible
Enrolled infants who did not have evidence of a Gram-negative bacteria present on a prospective tracheal aspirate culture obtained for this trial and thus were not eligible to receive study drug.
|
|---|---|---|---|---|---|---|
|
Pre-discharge Failed Audiology Examination
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: up to 1 year of agePopulation: No infants were enrolled into the observational arm. 1 of the 16 enrolled infants (treatment arm - 78mg) was withdrawn early from the trial by the medical team and was not assessed for this outcome.
Outcome measures
| Measure |
Treatment Arm - 78mg
n=3 Participants
The phase 1 trial will begin with a dose of 78mg. All treatment arms will administer study drug every 12 hours for up to 14 days (28 doses). Up to 6 infants in this arm will receive the 78mg dose of tobramycin solution for inhalation administered via vibrating mesh nebulizer. During the trial, infants in each treatment arm will undergo blood and tracheal aspirate sampling and respiratory mechanics measurements at pre-specified time points to assess dose safety and potential efficacy. Continuous pulse oximetry monitoring for the duration of the trial will also occur. Clinical data will also be recorded daily throughout the trial in all participants.
Tobramycin solution for inhalation 78mg dose: Inhaled tobramycin - 78mg administered every 12 hours for 14 days.
|
Treatment Arm - 150mg
n=3 Participants
If tolerability is demonstrated in the 78mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 150mg dose: Inhaled tobramycin - 150mg administered every 12 hours for 14 days.
|
Treatment Arm - 216mg
n=3 Participants
If tolerability is demonstrated in the 150mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 216mg dose: Inhaled tobramycin - 216mg administered every 12 hours for 14 days.
|
Treatment Arm - 300mg
n=6 Participants
If tolerability is demonstrated in the 216mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 300mg dose: Inhaled tobramycin - 300mg administered every 12 hours for 14 days.
|
Observational Arm
Enrolled infants who are eligible to participate in the phase-1 trial may be enrolled in an untreated observational cohort at parental discretion. This cohort will undergo collection of clinical and respiratory mechanics data for 14 days after enrollment but will not receive the study drug.
|
Screened But Not Eligible
Enrolled infants who did not have evidence of a Gram-negative bacteria present on a prospective tracheal aspirate culture obtained for this trial and thus were not eligible to receive study drug.
|
|---|---|---|---|---|---|---|
|
New Intra-patient Microbial Resistance to Tobramycin During the Primary Hospitalization
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: During the 14-day trialPopulation: CFU counts were not measured by the microbiology lab on tracheal aspirate samples; only presence/absence of pathogens was recorded owing to variable consistency of sputum samples. No infants were enrolled into the observational arm.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: During the 14-day trialOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: During the 14-day trialOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: During the 14-day trialOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: During the 14-day trialOutcome measures
Outcome data not reported
Adverse Events
Treatment Arm - 78mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 2 deaths
Treatment Arm - 150mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Treatment Arm - 216mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 1 deaths
Treatment Arm - 300mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 1 deaths
Observational Arm
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Screened But Not Eligible
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment Arm - 78mg
n=4 participants at risk
The phase 1 trial will begin with a dose of 78mg. All treatment arms will administer study drug every 12 hours for up to 14 days (28 doses). Up to 6 infants in this arm will receive the 78mg dose of tobramycin solution for inhalation administered via vibrating mesh nebulizer. During the trial, infants in each treatment arm will undergo blood and tracheal aspirate sampling and respiratory mechanics measurements at pre-specified time points to assess dose safety and potential efficacy. Continuous pulse oximetry monitoring for the duration of the trial will also occur. Clinical data will also be recorded daily throughout the trial in all participants.
Tobramycin solution for inhalation 78mg dose: Inhaled tobramycin - 78mg administered every 12 hours for 14 days.
|
Treatment Arm - 150mg
n=3 participants at risk
If tolerability is demonstrated in the 78mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 150mg dose: Inhaled tobramycin - 150mg administered every 12 hours for 14 days.
|
Treatment Arm - 216mg
n=3 participants at risk
If tolerability is demonstrated in the 150mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 216mg dose: Inhaled tobramycin - 216mg administered every 12 hours for 14 days.
|
Treatment Arm - 300mg
n=6 participants at risk
If tolerability is demonstrated in the 216mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.
Tobramycin solution for inhalation 300mg dose: Inhaled tobramycin - 300mg administered every 12 hours for 14 days.
|
Observational Arm
Enrolled infants who are eligible to participate in the phase-1 trial may be enrolled in an untreated observational cohort at parental discretion. This cohort will undergo collection of clinical and respiratory mechanics data for 14 days after enrollment but will not receive the study drug.
|
Screened But Not Eligible
Enrolled infants who did not have evidence of a Gram-negative bacteria present on a prospective tracheal aspirate culture obtained for this trial and thus were not eligible to receive study drug.
|
|---|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Desturation episode outside of study drug administration
|
0.00%
0/4 • During the 14 day drug trial and continuing until hospital discharge
Adverse event data was not captured on infants who were screened but not enrolled into the drug trial.
|
33.3%
1/3 • Number of events 1 • During the 14 day drug trial and continuing until hospital discharge
Adverse event data was not captured on infants who were screened but not enrolled into the drug trial.
|
33.3%
1/3 • Number of events 1 • During the 14 day drug trial and continuing until hospital discharge
Adverse event data was not captured on infants who were screened but not enrolled into the drug trial.
|
16.7%
1/6 • Number of events 1 • During the 14 day drug trial and continuing until hospital discharge
Adverse event data was not captured on infants who were screened but not enrolled into the drug trial.
|
—
0/0 • During the 14 day drug trial and continuing until hospital discharge
Adverse event data was not captured on infants who were screened but not enrolled into the drug trial.
|
—
0/0 • During the 14 day drug trial and continuing until hospital discharge
Adverse event data was not captured on infants who were screened but not enrolled into the drug trial.
|
Additional Information
Erik Jensen, MD, MSCE
Stanford University School of Medicine
Phone: 267-648-2720
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place