Inhaled Tobramycin in BPD

Bronchopulmonary Dysplasia Clinical Trial

Official title:

Phase 1 Feasibility Trial of Inhaled Tobramycin in Preterm Infants With Bronchopulmonary Dysplasia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04560179
• Other study ID #: 19-016800
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 22, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 27
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Weeks and older

Eligibility

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.

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia

Intervention

Drug:
• Tobramycin solution for inhalation 78mg dose
Inhaled tobramycin - 78mg administered every 12 hours for 14 days.
• Tobramycin solution for inhalation 150mg dose
Inhaled tobramycin - 150mg administered every 12 hours for 14 days.
• Tobramycin solution for inhalation 216mg dose
Inhaled tobramycin - 216mg administered every 12 hours for 14 days.
• Tobramycin solution for inhalation 300mg dose
Inhaled tobramycin - 300mg administered every 12 hours for 14 days.

Locations

Country	Name	City	State
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Erik Allen Jensen	University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Any time during the 14-day trial
Secondary	New onset or worsened coughing associated with a change in respiratory status (SpO2 <80% for >10 seconds; need for increase in FiO2 by >20%)		Any time during the 14-day trial
Secondary	Obstruction of the endotracheal tube requiring tube replacement		Any time during the 14-day trial
Secondary	Unplanned tracheal extubation		Any time during the 14-day trial
Secondary	Desaturation (SpO2 <80% for >10 seconds) during administration of inhaled tobramycin		Any time during the 14 day trial
Secondary	Pre-discharge failed audiology examination		up to 1 year of age
Secondary	New intra-patient microbial resistance to tobramycin during the primary hospitalization		up to 1 year of age
Secondary	Change in tracheal aspirate pathogenic bacterial colony forming unit (CFU) counts measured by quantitative culture		During the 14-day trial
Secondary	Change in the fraction of inspired oxygen (FiO2), ventilator mean airway pressure (MAP), and respiratory severity score (MAP x FiO2)		During the 14-day trial
Secondary	Change in intermittent hypoxemia (SpO2<80% lasting >/=10s), prolonged hypoxemia (SpO2<80% lasting >1min), and daily proportion of time in hypoxemia		During the 14-day trial
Secondary	Change in tracheal aspirate cytokine levels, neutrophil to total WBC ratio, and patterns in the airway microbiome		During the 14-day trial
Secondary	Change in dynamic lung compliance, airway resistance, peak expiratory flow, and carbon dioxide (CO2) elimination		During the 14-day trial