Bronchopulmonary Dysplasia
Conditions
Keywords
Bronchopulmonary Dysplasia, Neonates
Brief summary
The primary study objective is to assess the safety and feasibility of perfluorooctylbromide (PFOB) partial liquid ventilation (PLV) in infants with severe Bronchopulmonary Dysplasia (BPD).
Detailed description
The primary study objective is to assess the safety and feasibility of perfluorooctylbromide (PFOB) partial liquid ventilation for up to ten days in infants with severe BPD as evaluated by: (1) no sustained oxygen desaturations (SpO2 ≤ 80%) for greater than ten minutes without response to increased oxygen therapy, (2) no persistent hypotension without response to volume expansion and/or inotropic therapy, (3) no major mucus plugging events (defined as events that are unresolved after two bronchoscopes), (4) no pneumothoraces or pleural effusion with PFOB, (5) and no evidence of increased carbon dioxide (CO2) retention, renal insufficiency, hyperkalemia, or metabolic acidosis.
Interventions
DRUGPerfluorooctyl Bromide
Subjects in the PFOB group will receive PFOB partial liquid ventilation instilled via side port of endotracheal tube (2.5 mL/kg/day) across 10 treatment days.
Sponsors
Auto Dealers Caring for Kids Foundation
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 6 Months
Healthy volunteers
No
Inclusion criteria
1. Neonates with severe BPD as defined by 36 weeks post conception age and require positive pressure ventilation 2. Infants born at less than 32 weeks post conception age 3. Subjects may be up to 6 months corrected age 4. On conventional mechanical ventilation for chronic lung disease for at least two days prior to enrollment 5. On conventional mechanical ventilation at the time of enrollment and anticipated to continue for 14 days 6. Off systemic steroids for lung disease for 72 hours (3 days) prior to T=0 7. Hemoglobin value ≥8 g/dL: if less than 8 g/dL, transfusion is permitted. Clinical blood transfusion should be administered prior to enrollment. 8. Parental/guardian permission (informed consent)
Exclusion criteria
1. Mechanical ventilation for acute disease, such as for infection or for post-operative complications 2. Severe Pulmonary Hypertension (PAH) (pulmonary pressure greater than 2/3 systemic) as defined by either echocardiogram (ECHO), or cardiac catheterizations or a CT-Angiogram consistent with PAH within the last 3 weeks. 3. Pneumothorax (active air leak) requiring chest tube within 72 hours of T=0 4. Active pulmonary hemorrhage within 72 hours of T=0 5. History of Grade III/IV interventricular hemorrhage without resolution or stability within 3 weeks of verifying eligibility 6. Severe congenital heart disease compromising pulmonary circulation 7. Other major congenital malformation (including but not limited to CDH) or known genetic syndromes at the discretion of the investigator 8. Use of an investigational drug within 7 days prior to confirmation of eligibility. 9. The clinical attending physician believes it is not in the subject's and/or parents/guardians best interest to participate in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with sustained hypercapnia (elevated carbon dioxide in the blood, greater than 95 mmHg, for over four hours). | Day 5, Day 10 | Hypercapnia will be measured with blood tests and/or cutaneous carbon dioxide monitor. |
| Persistent hypotension without response to volume expansion and/or inotropic therapy | Day 5, Day 10 | Incidence of persistent hypotension without response to volume expansion and/or inotropic therapy. Hypotension is a decrease in systolic blood pressure deemed significant by clinical staff. Measurement will be performed with a standard intensive care unit blood pressure cuff. |
| Change in number of major mucus plugging events | Day 5, Day 10 | Incidence of airway obstruction of the endotracheal tube, as indicated by decreased chest movement during mechanical ventilation, need for increased ventilator pressure, and/or elevation of carbon dioxide levels in the blood. Mucus plugs are confirmed by endotracheal suctioning. |
| Incidence of pneumothorax or pleural effusion with PFOB | Day 5, Day 10 | Incidence of pneumothorax in the child will be measured by transillumination of the chest and confirmed by chest x-ray. |
| Sustained oxygen desaturations for greater than ten minutes without response to increased oxygen therapy | Day 5, Day 10 | Incidence of sustained (greater than 10 minutes) oxygen desaturation events without response to increased oxygen therapy. These incidences will be measured by a continuous non-invasive percutaneous oxygen saturation monitor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in ventilator mean airway pressure (MAP) | Day 5, Day 10 | Mean airway pressure (MAP) is the average amount of airway pressure supplied to the lungs throughout a breath. Higher MAP indicates more severe disease. |
| Change in Respiratory Severity Score (MAP x FiO2) | Day 5, Day 10 | Respiratory Severity Score (RSS) is a scale computed as the Mean Airway Pressure (MAP) multiplied by the Fraction of Inspired Oxygen (FiO2). Clinically, the scale range will often lie between 1 and 10, with higher numbers indicating more severe disease. The RSS can theoretically reach a score as high as 30-35. |
| Change in fraction of inspired oxygen (FiO2) | Day 5, Day 10 | Fraction of inspired oxygen is the percentage of oxygen that the patient is receiving for his or her lung disease. An FiO2 of 0.21 is room air oxygen and 1.00 is 100% oxygen. The higher the FiO2, the more severe the respiratory disease. |
Countries
United States
Outcome results
None listed