Bronchopulmonary Dysplasia
Conditions
Keywords
bronchopulmonary dysplasia, respiratory failure
Brief summary
The primary objective of this study is to provide expanded access of S-nitrosylation therapy for the treatment of bronchopulmonary dysplasia
Detailed description
Open label study with 20 participants, open-label, with block dose escalation of 3 subjects/dose (0.5 mL/kg of 0.25 mM, 0.5 mM, or 1 mM). A minimum of seven days of surveillance will separate dosing blocks. An additional 11 subjects will be enrolled at the maximum 1 mM block (5x10-7 moles/kg). The primary outcomes are safety during 30 minutes of inhalation, and for 4 hours after inhalation, as measured by occurrence of adverse events related to the treatment + time period \[during administration and tracked for next 7 days\].
Interventions
DRUGGSNO
Intervention will be 30 minutes of inhaled GSNO agent in enrollment blocks of three subjects/dose (0.5 mL/kg of 0.25 mM, 0.5 mM, or 1 mM) to infants.
Sponsors
University Hospitals Cleveland Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
29 Days to 365 Days
Healthy volunteers
No
Inclusion criteria
1. Inborn or outborn infants of either sex or any race or ethnicity 2. \<32 weeks gestation at birth (best obstetrical dating) 3. Aged 29 to 365 days 4. Refractory hypoxic respiratory failure (average daily FiO2 \>35% for 5 days) 5. Requires mechanical ventilation via endotracheal airway
Exclusion criteria
1. Life-threatening congenital or acquired anomalies (lethal chromosomal, thoracic/cardiac, brain) 2. Unstable condition defined as severe hypoxemia (FiO2 \>85% for \>24hrs), sepsis, or hypotension 3. Baseline methemoglobin \> 3%, congenital methemoglobinemia, or a familial hemoglobinopathy 4. On steroid to facilitate endotracheal extubation 5. Individuals on inhaled nitric oxide, a phosphodiesterase 5 (PDE-5) inhibitor, taking allopurinol, β-adrenergic blockers, tricyclic antidepressants, meperidine (or related CNS agents), or nitrates 6. Thrombocytopenia defined as \<50,000 platelets/µL on weekly NICU labs, clinical evidence of bleeding, on an anti-coagulant, or individuals with an inherited or acquired coagulation disorder 7. Anemia defined as a hemoglobin of \< 9 mg/dL on weekly NICU labs 8. Concerns for pre-existing liver damage defined as an AST/ALT \> 50 IU/L or direct bilirubin \>1 mg/dL on weekly NICU labs 9. Concerns for acute kidney injury defined as a serum creatinine \> 0.7 mg/dL on weekly NICU labs or 24-hr urine output \<1.0 ml/kg/hr during preceding 4 days 10. Patients that are ventilated with a device not certified for blending of aerosolized solutions into the ventilator circuit 11. Physician of record opposed to enrolling the patient due to perceived safety concerns; or any condition that does not allow the protocol to be followed safely 12. Subjects that have experienced cardiac arrest with CPR for longer than 30 minutes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Emergent Adverse Events | 7 days | Occurrence of \>grade 3 adverse events related to the treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| S-nitrosoglutathione change | 30 minutes | Percent change in S-nitrosoglutathione pre/post treatment |
| Change in oxygen saturation index | 4 hours | Percent change in oxygen saturation index (O.S.I.) pre/post treatment. oxygen saturation index \[O.S.I. = (FiO2) x (mean airway pressure) x 100 / (SpO2)\]. High OSI scores indicate worse respiratory failure (high OSI = bad, low OSI = good).Scale range: zero - infinity |
| Change in GSNO catabolism pre/post treatment | 30 minutes | Percent change in GSNO catabolism pre/post treatment |
| Intermittent hypoxemia as measured by oxygen saturation post treatment | 4 hours | Incidence, duration, and nadirs of intermittent hypoxemia (SpO2 \<80%) as measured by oxygen saturation parameters post treatment |
| Ventilator parameters post treatment | 4 hours | Change in ventilator parameters post treatment |
Countries
United States
Outcome results
None listed