Inhaled Tobramycin in BPD

NCT ID: NCT04560179

Last Updated: 2025-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-22
• Study Completion Date: 2024-05-17

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.

Conditions

Bronchopulmonary Dysplasia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Tobramycin solution for inhalation 78mg dose

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

Tobramycin solution for inhalation 150mg dose

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

Tobramycin solution for inhalation 216mg dose

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

Tobramycin solution for inhalation 300mg dose

Intervention Type: DRUG

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Tobramycin solution for inhalation 78mg dose

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

Intervention Type: DRUG

Tobramycin solution for inhalation 150mg dose

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

Intervention Type: DRUG

Tobramycin solution for inhalation 216mg dose

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

Intervention Type: DRUG

Tobramycin solution for inhalation 300mg dose

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 4 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Florida

OTHER

Sponsor Role: collaborator

Erik Allen Jensen

OTHER

Sponsor Role: lead

Responsible Party

Erik Allen Jensen

Assistant Professor of Pediatrics / Attending Neonatologist

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

19-016800

Identifier Type: -

Identifier Source: org_study_id