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CompletedNCT04560179Updated Jan 31, 2025Results posted

Inhaled Tobramycin in BPD

A Phase 1 interventional study of Tobramycin solution for inhalation 78mg dose and Tobramycin solution for inhalation 150mg dose in Bronchopulmonary Dysplasia, sponsored by Erik Allen Jensen. Completed at 1 site in United States. Open to participants aged 4 Weeks and older. Per ClinicalTrials.gov, last updated 2025-01-31.

Sponsored by Erik Allen Jensen · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
27
Allocation
Non-randomized
Ages
4 Weeks and older
Sex
All
01

Study summary

This study is an open-label, phase 1, sequential dose escalation trial seeking to establish preliminary tolerability, efficacy, and pharmacokinetic data for up to 4 different doses of inhaled tobramycin administered to very preterm infants with BPD who are receiving invasive mechanical ventilation and have a pathogenic Gram-negative organism detected by tracheal aspirate culture.

02

Conditions studied

  • Bronchopulmonary Dysplasia
03

In context

Bronchopulmonary Dysplasia

339 studies on the registry are indexed under Bronchopulmonary Dysplasia; 80 are open to participants now.

This study's enrollment of 27 is below the median of 70 across 228 interventional studies indexed under Bronchopulmonary Dysplasia.

Browse Bronchopulmonary Dysplasia studies →

Lead sponsor

This is the only study on the registry with Erik Allen Jensen as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
4 Weeks and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Male or female infants born \<32 weeks' gestation
  2. Diagnosed with BPD (use of supplemental oxygen or respiratory support at 36 weeks postmenstrual age )
  3. Postmenstrual age ≥36 weeks at study enrollment
  4. Treatment with invasive mechanical ventilation at enrollment without planned tracheal extubation within 7 days after enrollment
  5. Tracheal aspirate culture positive for one of the following pathogenic GNR bacteria within 7 days prior to enrollment: Pseudomonas aeruginosa, Klebsiella species, Enterobacter species, Stenotrophomonas maltophilia, Escherichia coli, Acinetobacter baumannii, or Serratia marcescens
  6. Parental/guardian permission (informed consent).

Exclusion criteria

Exclusion Criteria:

  1. Serum creatinine >0.4mg/dL within 14 days prior to enrollment
  2. Congenital or acquired disease of the kidney or renal collecting system that adversely affects renal function
  3. Congenital or acquired hepatobiliary disease that adversely affects liver function
  4. Treatment with a systemic antibiotic within 7 days prior to enrollment
  5. Treatment with a nephrotoxic medication, excluding diuretics, within 48 hours prior to enrollment
  6. Treatment with a neuromuscular blocker within 48 hours prior to enrollment
  7. Known intolerance to aminoglycoside antibiotics
  8. Current treatment with high frequency or other oscillating mechanical ventilation
  9. Presence of a cancer diagnosis
  10. Maternal family history of early onset hearing loss defined as the need for an assistive hearing device prescribed before 30 years of age
  11. Endotracheal tube leak >20%.
  12. Any prior use of an investigational drug [as part of an FDA approved Investigational New Drug (IND) protocol].
  13. A subject who, in the judgement of the Investigator, is not an appropriate candidate for this research study.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
27 participants (actual)

Study arms

  • Experimental
    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.

    Drug: Tobramycin solution for inhalation 78mg dose

  • Experimental
    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.

    Drug: Tobramycin solution for inhalation 150mg dose

  • Experimental
    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.

    Drug: Tobramycin solution for inhalation 216mg dose

  • Experimental
    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.

    Drug: Tobramycin solution for inhalation 300mg dose

  • No intervention
    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.

Interventions

  • DrugTobramycin solution for inhalation 78mg dose

    Inhaled tobramycin - 78mg administered every 12 hours for 14 days.

  • DrugTobramycin solution for inhalation 150mg dose

    Inhaled tobramycin - 150mg administered every 12 hours for 14 days.

  • DrugTobramycin solution for inhalation 216mg dose

    Inhaled tobramycin - 216mg administered every 12 hours for 14 days.

  • DrugTobramycin solution for inhalation 300mg dose

    Inhaled tobramycin - 300mg administered every 12 hours for 14 days.

06

What researchers measure

Primary outcomes

  1. Elevated Serum Tobramycin Trough or Creatinine or Severe Adverse Event

    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

    Time frame: Any time during the 14-day trial

Secondary outcomes

  1. New Onset or Worsened Coughing Associated With a Change in Respiratory Status (SpO2 <80% for >10 Seconds; Need for Increase in FiO2 by >20%)

    Time frame: Any time during the 14-day trial

  2. Obstruction of the Endotracheal Tube Requiring Tube Replacement

    Time frame: Any time during the 14-day trial

  3. Unplanned Tracheal Extubation

    Time frame: Any time during the 14-day trial

  4. Desaturation (SpO2 <80% for >10 Seconds) During Administration of Inhaled Tobramycin

    Time frame: Any time during the 14 day trial

  5. Pre-discharge Failed Audiology Examination

    Time frame: up to 1 year of age

  6. New Intra-patient Microbial Resistance to Tobramycin During the Primary Hospitalization

    Time frame: up to 1 year of age

  7. Change in Tracheal Aspirate Pathogenic Bacterial Colony Forming Unit (CFU) Counts Measured by Quantitative Culture

    Time frame: During the 14-day trial

  8. Change in the Fraction of Inspired Oxygen (FiO2), Ventilator Mean Airway Pressure (MAP), and Respiratory Severity Score (MAP x FiO2)

    Time frame: During the 14-day trial

  9. Change in Intermittent Hypoxemia (SpO2<80% Lasting >/=10s), Prolonged Hypoxemia (SpO2<80% Lasting >1min), and Daily Proportion of Time in Hypoxemia

    Time frame: During the 14-day trial

  10. Change in Tracheal Aspirate Cytokine Levels, Neutrophil to Total WBC Ratio, and Patterns in the Airway Microbiome

    Time frame: During the 14-day trial

  11. Change in Dynamic Lung Compliance, Airway Resistance, Peak Expiratory Flow, and Carbon Dioxide (CO2) Elimination

    Time frame: During the 14-day trial

07

Results

Posted Jan 31, 2025

Participant flow

Participant flow — Overall Study
MilestoneTreatment Arm - 78mgTreatment Arm - 150mgTreatment Arm - 216mgTreatment Arm - 300mgObservational Arm
Started43360
Completed33350
Not completed10010
Withdrew: Physician decision10000
Withdrew: Adverse event00010

Outcome measures

PrimaryElevated Serum Tobramycin Trough or Creatinine or Severe Adverse Event

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

Time frame:
Any time during the 14-day trial
Reported as:
Count of participants · Participants
Elevated Serum Tobramycin Trough or Creatinine or Severe Adverse Event
ParticipantsTreatment Arm - 78mgTreatment Arm - 150mgTreatment Arm - 216mgTreatment Arm - 300mgObservational Arm
Elevated Serum Tobramycin Trough or Creatinine or Severe Adverse Event00010
SecondaryNew Onset or Worsened Coughing Associated With a Change in Respiratory Status (SpO2 <80% for >10 Seconds; Need for Increase in FiO2 by >20%)
Time frame:
Any time during the 14-day trial
Reported as:
Count of participants · Participants
New Onset or Worsened Coughing Associated With a Change in Respiratory Status (SpO2 <80% for >10 Seconds; Need for Increase in FiO2 by >20%)
ParticipantsTreatment Arm - 78mgTreatment Arm - 150mgTreatment Arm - 216mgTreatment Arm - 300mgObservational Arm
New Onset or Worsened Coughing Associated With a Change in Respiratory Status (SpO2 <80% for >10 Seconds; Need for Increase in FiO2 by >20%)00000
SecondaryObstruction of the Endotracheal Tube Requiring Tube Replacement
Time frame:
Any time during the 14-day trial
Reported as:
Count of participants · Participants
Obstruction of the Endotracheal Tube Requiring Tube Replacement
ParticipantsTreatment Arm - 78mgTreatment Arm - 150mgTreatment Arm - 216mgTreatment Arm - 300mgObservational Arm
Obstruction of the Endotracheal Tube Requiring Tube Replacement00000
SecondaryUnplanned Tracheal Extubation
Time frame:
Any time during the 14-day trial
Reported as:
Count of participants · Participants
Unplanned Tracheal Extubation
ParticipantsTreatment Arm - 78mgTreatment Arm - 150mgTreatment Arm - 216mgTreatment Arm - 300mgObservational Arm
Unplanned Tracheal Extubation00000
SecondaryDesaturation (SpO2 <80% for >10 Seconds) During Administration of Inhaled Tobramycin
Time frame:
Any time during the 14 day trial
Reported as:
Count of participants · Participants
Desaturation (SpO2 <80% for >10 Seconds) During Administration of Inhaled Tobramycin
ParticipantsTreatment Arm - 78mgTreatment Arm - 150mgTreatment Arm - 216mgTreatment Arm - 300mgObservational ArmScreened But Not Eligible
Desaturation (SpO2 <80% for >10 Seconds) During Administration of Inhaled Tobramycin301000
SecondaryPre-discharge Failed Audiology Examination
Time frame:
up to 1 year of age
Reported as:
Count of participants · Participants
Pre-discharge Failed Audiology Examination
ParticipantsTreatment Arm - 78mgTreatment Arm - 150mgTreatment Arm - 216mgTreatment Arm - 300mgObservational Arm
Pre-discharge Failed Audiology Examination11010
SecondaryNew Intra-patient Microbial Resistance to Tobramycin During the Primary Hospitalization
Time frame:
up to 1 year of age
Reported as:
Count of participants · Participants
New Intra-patient Microbial Resistance to Tobramycin During the Primary Hospitalization
ParticipantsTreatment Arm - 78mgTreatment Arm - 150mgTreatment Arm - 216mgTreatment Arm - 300mgObservational Arm
New Intra-patient Microbial Resistance to Tobramycin During the Primary Hospitalization00000
SecondaryChange in Tracheal Aspirate Pathogenic Bacterial Colony Forming Unit (CFU) Counts Measured by Quantitative Culture
Time frame:
During the 14-day trial

No measurements were reported for this outcome.

SecondaryChange in the Fraction of Inspired Oxygen (FiO2), Ventilator Mean Airway Pressure (MAP), and Respiratory Severity Score (MAP x FiO2)
Time frame:
During the 14-day trial

Results for this outcome have not been posted.

SecondaryChange in Intermittent Hypoxemia (SpO2<80% Lasting >/=10s), Prolonged Hypoxemia (SpO2<80% Lasting >1min), and Daily Proportion of Time in Hypoxemia
Time frame:
During the 14-day trial

Results for this outcome have not been posted.

SecondaryChange in Tracheal Aspirate Cytokine Levels, Neutrophil to Total WBC Ratio, and Patterns in the Airway Microbiome
Time frame:
During the 14-day trial

Results for this outcome have not been posted.

SecondaryChange in Dynamic Lung Compliance, Airway Resistance, Peak Expiratory Flow, and Carbon Dioxide (CO2) Elimination
Time frame:
During the 14-day trial

Results for this outcome have not been posted.

Adverse events

Collected over During the 14 day drug trial and continuing until hospital discharge. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment Arm - 78mg2/4 (50%)0/4 (0%)0/4 (0%)
Treatment Arm - 150mg0/3 (0%)0/3 (0%)1/3 (33.3%)
Treatment Arm - 216mg1/3 (33.3%)0/3 (0%)1/3 (33.3%)
Treatment Arm - 300mg1/6 (16.7%)0/6 (0%)1/6 (16.7%)
Observational Arm———
Screened But Not Eligible———
Most frequent other events
Most frequent other events
EventTreatment Arm - 78mgTreatment Arm - 150mgTreatment Arm - 216mgTreatment Arm - 300mgObservational ArmScreened But Not Eligible
Desturation episode outside of study drug administrationRespiratory, thoracic and mediastinal disorders0/41/31/31/6——

Baseline characteristics

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.

Age, Categorical
Age, Categorical(Participants)Treatment Arm - 78mgTreatment Arm - 150mgTreatment Arm - 216mgTreatment Arm - 300mgObservational ArmTotal
<=18 years4336016
Between 18 and 65 years000000
>=65 years000000
Sex: Female, Male
Sex: Female, Male(Participants)Treatment Arm - 78mgTreatment Arm - 150mgTreatment Arm - 216mgTreatment Arm - 300mgObservational ArmTotal
Female122207
Male311409
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Treatment Arm - 78mgTreatment Arm - 150mgTreatment Arm - 216mgTreatment Arm - 300mgObservational ArmTotal
Hispanic or Latino300104
Not Hispanic or Latino1335012
Unknown or Not Reported000000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment Arm - 78mgTreatment Arm - 150mgTreatment Arm - 216mgTreatment Arm - 300mgObservational ArmTotal
American Indian or Alaska Native000000
Asian000000
Native Hawaiian or Other Pacific Islander000000
Black or African American3332011
White100102
More than one race000000
Unknown or Not Reported000303
Region of Enrollment
Region of Enrollment(participants)Treatment Arm - 78mgTreatment Arm - 150mgTreatment Arm - 216mgTreatment Arm - 300mgObservational ArmTotal
United States4336—16
08

Study locations

1 site
  • The Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19104, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Jun 20, 2023

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 31, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04560179
Lead sponsor
Erik Allen Jensen
Collaborators
University of Florida
Responsible party
Erik Allen Jensen (Assistant Professor of Pediatrics / Attending Neonatologist, Children's Hospital of Philadelphia) — Sponsor-investigator
First posted
Sep 23, 2020
Start date
Mar 22, 2022
Primary completion
Dec 31, 2023
Completion
May 17, 2024
Results posted
Jan 31, 2025
Last update
Jan 31, 2025

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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