Back to resultsInhaled Tobramycin in BPD
Primary Purpose
Bronchopulmonary Dysplasia
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Tobramycin solution for inhalation 78mg dose
Tobramycin solution for inhalation 150mg dose
Tobramycin solution for inhalation 216mg dose
Tobramycin solution for inhalation 300mg dose
Sponsored by
About this trial
This is an interventional treatment trial for Bronchopulmonary Dysplasia
Eligibility Criteria
Inclusion Criteria:
- Male or female infants born <32 weeks' gestation
- Diagnosed with BPD (use of supplemental oxygen or respiratory support at 36 weeks postmenstrual age )
- Postmenstrual age ≥36 weeks at study enrollment
- Treatment with invasive mechanical ventilation at enrollment without planned tracheal extubation within 7 days after enrollment
- 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
- Parental/guardian permission (informed consent).
Exclusion Criteria:
- Serum creatinine >0.4mg/dL within 14 days prior to enrollment
- Congenital or acquired disease of the kidney or renal collecting system that adversely affects renal function
- Congenital or acquired hepatobiliary disease that adversely affects liver function
- Treatment with a systemic antibiotic within 7 days prior to enrollment
- Treatment with a nephrotoxic medication, excluding diuretics, within 48 hours prior to enrollment
- Treatment with a neuromuscular blocker within 48 hours prior to enrollment
- Known intolerance to aminoglycoside antibiotics
- Current treatment with high frequency or other oscillating mechanical ventilation
- Presence of a cancer diagnosis
- Maternal family history of early onset hearing loss defined as the need for an assistive hearing device prescribed before 30 years of age
- Endotracheal tube leak >20%.
- Any prior use of an investigational drug [as part of an FDA approved Investigational New Drug (IND) protocol].
- A subject who, in the judgement of the Investigator, is not an appropriate candidate for this research study.
Sites / Locations
- The Children's Hospital of PhiladelphiaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
No Intervention
Arm Label
Treatment Arm - 78mg
Treatment Arm - 150mg
Treatment Arm - 216mg
Treatment Arm - 300mg
Observational Arm
Arm Description
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.
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
New onset or worsened coughing associated with a change in respiratory status (SpO2 <80% for >10 seconds; need for increase in FiO2 by >20%)
Obstruction of the endotracheal tube requiring tube replacement
Unplanned tracheal extubation
Desaturation (SpO2 <80% for >10 seconds) during administration of inhaled tobramycin
Pre-discharge failed audiology examination
New intra-patient microbial resistance to tobramycin during the primary hospitalization
Change in tracheal aspirate pathogenic bacterial colony forming unit (CFU) counts measured by quantitative culture
Change in the fraction of inspired oxygen (FiO2), ventilator mean airway pressure (MAP), and respiratory severity score (MAP x FiO2)
Change in intermittent hypoxemia (SpO2<80% lasting >/=10s), prolonged hypoxemia (SpO2<80% lasting >1min), and daily proportion of time in hypoxemia
Change in tracheal aspirate cytokine levels, neutrophil to total WBC ratio, and patterns in the airway microbiome
Change in dynamic lung compliance, airway resistance, peak expiratory flow, and carbon dioxide (CO2) elimination
Full Information
NCT ID
NCT04560179
First Posted
September 17, 2020
Last Updated
April 27, 2023
Sponsor
Erik Allen Jensen
Collaborators
University of Florida
1. Study Identification
Unique Protocol Identification Number
NCT04560179
Brief Title
Inhaled Tobramycin in BPD
Official Title
Phase 1 Feasibility Trial of Inhaled Tobramycin in Preterm Infants With Bronchopulmonary Dysplasia
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 22, 2022 (Actual)
Primary Completion Date
August 30, 2024 (Anticipated)
Study Completion Date
March 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Erik Allen Jensen
Collaborators
University of Florida
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchopulmonary Dysplasia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
3+3 dose escalation trial.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
54 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment Arm - 78mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Treatment Arm - 150mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Treatment Arm - 216mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Treatment Arm - 300mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Observational Arm
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tobramycin solution for inhalation 78mg dose
Intervention Description
Inhaled tobramycin - 78mg administered every 12 hours for 14 days.
Intervention Type
Drug
Intervention Name(s)
Tobramycin solution for inhalation 150mg dose
Intervention Description
Inhaled tobramycin - 150mg administered every 12 hours for 14 days.
Intervention Type
Drug
Intervention Name(s)
Tobramycin solution for inhalation 216mg dose
Intervention Description
Inhaled tobramycin - 216mg administered every 12 hours for 14 days.
Intervention Type
Drug
Intervention Name(s)
Tobramycin solution for inhalation 300mg dose
Intervention Description
Inhaled tobramycin - 300mg administered every 12 hours for 14 days.
Primary Outcome Measure Information:
Title
Elevated serum tobramycin trough or creatinine or severe adverse event
Description
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 Outcome Measure Information:
Title
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
Title
Obstruction of the endotracheal tube requiring tube replacement
Time Frame
Any time during the 14-day trial
Title
Unplanned tracheal extubation
Time Frame
Any time during the 14-day trial
Title
Desaturation (SpO2 <80% for >10 seconds) during administration of inhaled tobramycin
Time Frame
Any time during the 14 day trial
Title
Pre-discharge failed audiology examination
Time Frame
up to 1 year of age
Title
New intra-patient microbial resistance to tobramycin during the primary hospitalization
Time Frame
up to 1 year of age
Title
Change in tracheal aspirate pathogenic bacterial colony forming unit (CFU) counts measured by quantitative culture
Time Frame
During the 14-day trial
Title
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
Title
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
Title
Change in tracheal aspirate cytokine levels, neutrophil to total WBC ratio, and patterns in the airway microbiome
Time Frame
During the 14-day trial
Title
Change in dynamic lung compliance, airway resistance, peak expiratory flow, and carbon dioxide (CO2) elimination
Time Frame
During the 14-day trial
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Weeks
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female infants born <32 weeks' gestation
Diagnosed with BPD (use of supplemental oxygen or respiratory support at 36 weeks postmenstrual age )
Postmenstrual age ≥36 weeks at study enrollment
Treatment with invasive mechanical ventilation at enrollment without planned tracheal extubation within 7 days after enrollment
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
Parental/guardian permission (informed consent).
Exclusion Criteria:
Serum creatinine >0.4mg/dL within 14 days prior to enrollment
Congenital or acquired disease of the kidney or renal collecting system that adversely affects renal function
Congenital or acquired hepatobiliary disease that adversely affects liver function
Treatment with a systemic antibiotic within 7 days prior to enrollment
Treatment with a nephrotoxic medication, excluding diuretics, within 48 hours prior to enrollment
Treatment with a neuromuscular blocker within 48 hours prior to enrollment
Known intolerance to aminoglycoside antibiotics
Current treatment with high frequency or other oscillating mechanical ventilation
Presence of a cancer diagnosis
Maternal family history of early onset hearing loss defined as the need for an assistive hearing device prescribed before 30 years of age
Endotracheal tube leak >20%.
Any prior use of an investigational drug [as part of an FDA approved Investigational New Drug (IND) protocol].
A subject who, in the judgement of the Investigator, is not an appropriate candidate for this research study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Erik A Jensen, MD MSCE
Phone
2676482720
Email
jensene@chop.edu
Facility Information:
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Erik A Jensen, MD
Phone
267-648-2720
Email
jensene@chop.edu
First Name & Middle Initial & Last Name & Degree
Erik A Jensen, MD
12. IPD Sharing Statement
Learn more about this trial
Inhaled Tobramycin in BPD
We'll reach out to this number within 24 hrs