Inhaled Tobramycin in BPD

December 30, 2024 updated by: Erik Allen Jensen

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
27

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

4 weeks and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Inhaled tobramycin - 78mg administered every 12 hours for 14 days.
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
Inhaled tobramycin - 150mg administered every 12 hours for 14 days.
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
Inhaled tobramycin - 216mg administered every 12 hours for 14 days.
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
Inhaled tobramycin - 300mg administered every 12 hours for 14 days.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Elevated Serum Tobramycin Trough or Creatinine or Severe Adverse Event
Time Frame: Any time during the 14-day trial
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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
Any time during the 14-day trial
Obstruction of the Endotracheal Tube Requiring Tube Replacement
Time Frame: Any time during the 14-day trial
Any time during the 14-day trial
Unplanned Tracheal Extubation
Time Frame: Any time during the 14-day trial
Any time during the 14-day trial
Desaturation (SpO2 <80% for >10 Seconds) During Administration of Inhaled Tobramycin
Time Frame: Any time during the 14 day trial
Any time during the 14 day trial
Pre-discharge Failed Audiology Examination
Time Frame: up to 1 year of age
up to 1 year of age
New Intra-patient Microbial Resistance to Tobramycin During the Primary Hospitalization
Time Frame: up to 1 year of age
up to 1 year of age
Change in Tracheal Aspirate Pathogenic Bacterial Colony Forming Unit (CFU) Counts Measured by Quantitative Culture
Time Frame: During the 14-day trial
During the 14-day trial
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
During the 14-day trial
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
During the 14-day trial
Change in Tracheal Aspirate Cytokine Levels, Neutrophil to Total WBC Ratio, and Patterns in the Airway Microbiome
Time Frame: During the 14-day trial
During the 14-day trial
Change in Dynamic Lung Compliance, Airway Resistance, Peak Expiratory Flow, and Carbon Dioxide (CO2) Elimination
Time Frame: During the 14-day trial
During the 14-day trial

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Erik Allen Jensen

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Florida

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 22, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 17, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 17, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 17, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 23, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 30, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 19-016800

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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