Phase 1 Feasibility Trial of Inhaled Tobramycin in Preterm Infants With Bronchopulmonary Dysplasia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Elevated Serum Tobramycin Trough or Creatinine or Severe Adverse Event
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Weeks 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female infants born <32 weeks' gestation
- •Diagnosed with BPD (use of supplemental oxygen or respiratory support at 36 weeks postmenstrual age )
- •Postmenstrual age ≥36 weeks at study enrollment
- •Treatment with invasive mechanical ventilation at enrollment without planned tracheal extubation within 7 days after enrollment
- •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
- •Parental/guardian permission (informed consent).
排除标准
- •Serum creatinine >0.4mg/dL within 14 days prior to enrollment
- •Congenital or acquired disease of the kidney or renal collecting system that adversely affects renal function
- •Congenital or acquired hepatobiliary disease that adversely affects liver function
- •Treatment with a systemic antibiotic within 7 days prior to enrollment
- •Treatment with a nephrotoxic medication, excluding diuretics, within 48 hours prior to enrollment
- •Treatment with a neuromuscular blocker within 48 hours prior to enrollment
- •Known intolerance to aminoglycoside antibiotics
- •Current treatment with high frequency or other oscillating mechanical ventilation
- •Presence of a cancer diagnosis
- •Maternal family history of early onset hearing loss defined as the need for an assistive hearing device prescribed before 30 years of age
- •Endotracheal tube leak >20%.
- •Any prior use of an investigational drug [as part of an FDA approved Investigational New Drug (IND) protocol].
- •A subject who, in the judgement of the Investigator, is not an appropriate candidate for this research study.
研究组 & 干预措施
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.
干预措施: Tobramycin solution for inhalation 78mg dose (Drug)
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.
干预措施: Tobramycin solution for inhalation 150mg dose (Drug)
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.
干预措施: Tobramycin solution for inhalation 216mg dose (Drug)
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.
干预措施: Tobramycin solution for inhalation 300mg dose (Drug)
结局指标
主要结局
Elevated Serum Tobramycin Trough or Creatinine or Severe Adverse Event
时间窗: 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
次要结局
- 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)
- Obstruction of the Endotracheal Tube Requiring Tube Replacement(Any time during the 14-day trial)
- Unplanned Tracheal Extubation(Any time during the 14-day trial)
- Desaturation (SpO2 <80% for >10 Seconds) During Administration of Inhaled Tobramycin(Any time during the 14 day trial)
- Pre-discharge Failed Audiology Examination(up to 1 year of age)
- New Intra-patient Microbial Resistance to Tobramycin During the Primary Hospitalization(up to 1 year of age)
- Change in Tracheal Aspirate Pathogenic Bacterial Colony Forming Unit (CFU) Counts Measured by Quantitative Culture(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)(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(During the 14-day trial)
- Change in Tracheal Aspirate Cytokine Levels, Neutrophil to Total WBC Ratio, and Patterns in the Airway Microbiome(During the 14-day trial)
- Change in Dynamic Lung Compliance, Airway Resistance, Peak Expiratory Flow, and Carbon Dioxide (CO2) Elimination(During the 14-day trial)
研究者
Erik Allen Jensen
Assistant Professor of Pediatrics / Attending Neonatologist
Children's Hospital of Philadelphia