Clinical trial NCT04560179: Inhaled Tobramycin in BPD
Official title: Phase 1 Feasibility Trial of Inhaled Tobramycin in Preterm Infants With Bronchopulmonary Dysplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bronchopulmonary Dysplasia
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: University of Florida
First posted: 2020-09-23
Enrollment: 27
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 3+3 dose escalation trial.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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:

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.

Primary outcomes:
measure: Elevated Serum Tobramycin Trough or Creatinine or Severe Adverse Event
timeFrame: Any time during the 14-day trial
Secondary outcomes:
measure: New Onset or Worsened Coughing Associated With a Change in Respiratory Status (SpO2 <80% for >10 Seconds; Need for Increase in FiO2 by >20%)
timeFrame: Any time during the 14-day trial
measure: Obstruction of the Endotracheal Tube Requiring Tube Replacement
timeFrame: Any time during the 14-day trial
measure: Unplanned Tracheal Extubation
timeFrame: Any time during the 14-day trial
measure: Desaturation (SpO2 <80% for >10 Seconds) During Administration of Inhaled Tobramycin
timeFrame: Any time during the 14 day trial
measure: Pre-discharge Failed Audiology Examination
timeFrame: up to 1 year of age
measure: New Intra-patient Microbial Resistance to Tobramycin During the Primary Hospitalization
timeFrame: up to 1 year of age
measure: Change in Tracheal Aspirate Pathogenic Bacterial Colony Forming Unit (CFU) Counts Measured by Quantitative Culture
timeFrame: During the 14-day trial
measure: Change in the Fraction of Inspired Oxygen (FiO2), Ventilator Mean Airway Pressure (MAP), and Respiratory Severity Score (MAP x FiO2)
timeFrame: During the 14-day trial
measure: Change in Intermittent Hypoxemia (SpO2<80% Lasting >/=10s), Prolonged Hypoxemia (SpO2<80% Lasting >1min), and Daily Proportion of Time in Hypoxemia
timeFrame: During the 14-day trial
measure: Change in Tracheal Aspirate Cytokine Levels, Neutrophil to Total WBC Ratio, and Patterns in the Airway Microbiome
timeFrame: During the 14-day trial
measure: Change in Dynamic Lung Compliance, Airway Resistance, Peak Expiratory Flow, and Carbon Dioxide (CO2) Elimination
timeFrame: During the 14-day trial
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
References: