Inhaled Tobramycin for Bronchopulmonary Dysplasia

Overseen By Erik A Jensen, MD MSCE

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Erik Allen Jensen

Must not be taking: Systemic antibiotics, Nephrotoxic drugs

Disqualifiers: Kidney disease, Liver disease, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of inhaled tobramycin, an antibiotic solution for inhalation, to aid very preterm infants with bronchopulmonary dysplasia (BPD) who require mechanical ventilation. Researchers are testing various doses to determine which is safe and potentially effective against specific bacterial lung infections. The trial includes several groups receiving different doses and one group observed without treatment. Infants born before 32 weeks with specific bacterial lung infections and on mechanical ventilation might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering a unique opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

Participants must stop taking any systemic antibiotics and nephrotoxic medications (except diuretics) within 7 days and 48 hours before enrollment, respectively.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that inhaled tobramycin has been studied for safety in very preterm infants with bronchopulmonary dysplasia (BPD). Tobramycin, an antibiotic, can be inhaled to directly target the lungs.

Previous studies have found that inhaled tobramycin is generally well-tolerated in similar groups. "Well-tolerated" means that most patients did not experience serious side effects. Some side effects, like coughing or a sore throat, have been reported, but these are uncommon.

As this is a phase 1 trial, the main goal is to assess the treatment's safety and how the body processes it. In this phase, small doses are tested to identify any negative effects. While some evidence suggests that inhaled tobramycin is safe, the trial is still in early stages to fully confirm its safety.

In summary, inhaled tobramycin appears promising for safe use, but more data is needed to confirm this for preterm infants with BPD. Researchers will closely monitor participants to ensure their safety throughout the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about inhaled tobramycin for bronchopulmonary dysplasia because it offers a unique delivery method compared to current options, which primarily involve systemic antibiotics or supportive care. Tobramycin is given directly through inhalation, potentially allowing higher local concentrations in the lungs while minimizing systemic side effects. This method could lead to more effective treatment with a quicker response time, as the medication targets the lungs directly where the inflammation occurs. Additionally, by using inhalation, there's hope for better tolerability and reduced risk of drug resistance compared to oral or intravenous antibiotics.

What evidence suggests that inhaled tobramycin could be an effective treatment for bronchopulmonary dysplasia?

Research has shown that inhaled tobramycin might help very preterm infants with bronchopulmonary dysplasia (BPD), particularly those with harmful lung bacteria. Early studies indicate that inhaled tobramycin targets these bacteria directly in the lungs, potentially improving breathing and lung health. This trial tests different doses of inhaled tobramycin to determine the safest and most effective dose. Previous patients demonstrated that tobramycin can be well-tolerated at various doses. The goal is to directly treat lung infections, potentially reducing the need for other treatments and improving outcomes for these infants. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for very preterm infants born before 32 weeks with Bronchopulmonary Dysplasia (BPD) on mechanical ventilation and a recent tracheal culture positive for certain bacteria. Infants must be at least 36 weeks postmenstrual age, without cancer, significant hearing loss in the family, kidney or liver disease, large endotracheal tube leaks, known drug intolerance or recent use of systemic antibiotics.

Inclusion Criteria

I was diagnosed with BPD and needed extra oxygen or help breathing at 36 weeks after conception.

I am on a ventilator and not expected to be taken off it within a week.

My baby was born before 32 weeks of pregnancy.

Exclusion Criteria

I haven't taken any kidney-damaging medications, except for water pills, in the last 2 days.

I am currently on a high-frequency ventilator.

A close female relative needed a hearing aid before age 30.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inhaled tobramycin at varying doses every 12 hours for up to 14 days

2 weeks

Continuous monitoring

Observational

Enrolled infants in the observational cohort undergo data collection for 14 days without receiving the study drug

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tobramycin solution for inhalation

Trial Overview The study tests four escalating doses of inhaled tobramycin in these infants to check tolerability and effectiveness against Gram-negative bacterial infections. It's an open-label phase 1 trial where each infant receives one dose level to gather initial data on how the drug works and its safety.

How Is the Trial Designed?

Group I: Treatment Arm - 78mg Experimental Treatment 1 Intervention

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 II: Treatment Arm - 300mg Experimental Treatment 1 Intervention

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 III: Treatment Arm - 216mg Experimental Treatment 1 Intervention

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 IV: Treatment Arm - 150mg Experimental Treatment 1 Intervention

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 V: Observational Arm Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Erik Allen Jensen

Lead Sponsor

Trials

1

Recruited

30+

University of Florida

Collaborator

Trials

1,428

Recruited

987,000+

Citations

1. app.trialscreen.org app.trialscreen.org/trials/phase-1-bronchopulmonary-dysplasia-inhaled-tobramycin-bpd-trial-nct04560179

Inhaled Tobramycin in BPD The open-label phase 1 trial explores up to 4 doses of inhaled tobramycin for treating bronchopulmonary dysplasia in very preterm infants.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04560179

Study Details | NCT04560179 | Inhaled Tobramycin in BPD This study is an open-label, phase 1, sequential dose escalation trial seeking to establish preliminary tolerability, efficacy, and pharmacokinetic data for up ...

3. reporter.nih.gov reporter.nih.gov/search/RugRabx6pUaarrly4KnIfw/project-details/10472648

Phase 1 trial of inhaled tobramycin in very preterm infants ... These data provide strong biological plausibility that inhaled tobramycin will benefit very preterm infants with BPD who have pathogenic GNR organisms cultured ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/79/NCT04560179/Prot_SAP_000.pdf

Phase 1 Feasibility Trial of Inhaled Tobramycin in Preterm ... ... trial is to identify a well-tolerated dose of tobramycin solution for inhalation for use in very preterm infants with BPD who are actively ...

5. stanfordhealthcare.org stanfordhealthcare.org/trials/i/NCT04560179.html

Inhaled Tobramycin in BPD This study is an open-label, phase 1, sequential dose escalation trial seeking to establish preliminary tolerability, efficacy, and pharmacokinetic data for up ...

6. trial.medpath.com trial.medpath.com/clinical-trial/e67e70894185784d/nct04560179-inhaled-tobramycin-preterm-infants-bronchopulmonary-dysplasia

Inhaled Tobramycin in BPD - MedPath This study is an open-label, phase 1, sequential dose escalation trial seeking to establish preliminary tolerability, efficacy, and pharmacokinetic data for ...

7. ctv.veeva.com ctv.veeva.com/study/inhaled-tobramycin-in-bpd

Inhaled Tobramycin in BPD - ClinicalTrials.Veeva Up to 6 infants in this arm will receive the 78mg dose of tobramycin solution for inhalation administered via vibrating mesh nebulizer.

8. mayoclinic.org mayoclinic.org/drugs-supplements/tobramycin-inhalation-route/description/drg-20072503

Tobramycin (inhalation route) - Side effects & dosage Safety and efficacy have not been established. ... Tobramycin inhalation solution is packaged in small plastic containers called ampules.