Inhaled Treatment for Bronchopulmonary Dysplasia

Study Overview
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Brief Summary
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The primary objective of this study is to provide expanded access of S-nitrosylation therapy for the treatment of bronchopulmonary dysplasia

Detailed Description
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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].

Official Title
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Pilot Study of an Inhaled Treatment for Bronchopulmonary Dysplasia

Conditions
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Bronchopulmonary Dysplasia

Intervention / Treatment
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* Drug: GSNO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inborn or outborn infants of either sex or any race or ethnicity <32 weeks gestation at birth (best obstetrical dating) Aged 29 to 365 days Refractory hypoxic respiratory failure (average daily FiO2 >35% for 5 days) Requires mechanical ventilation via endotracheal airway Exclusion Criteria: Life-threatening congenital or acquired anomalies (lethal chromosomal, thoracic/cardiac, brain) Unstable condition defined as severe hypoxemia (FiO2 >85% for >24hrs), sepsis, or hypotension Baseline methemoglobin > 3%, congenital methemoglobinemia, or a familial hemoglobinopathy On steroid to facilitate endotracheal extubation 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 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 Anemia defined as a hemoglobin of < 9 mg/dL on weekly NICU labs Concerns for pre-existing liver damage defined as an AST/ALT > 50 IU/L or direct bilirubin >1 mg/dL on weekly NICU labs 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 Patients that are ventilated with a device not certified for blending of aerosolized solutions into the ventilator circuit 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 Subjects that have experienced cardiac arrest with CPR for longer than 30 minutes

Ages Eligible for Study
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Minimum Age: 29 Days
Maximum Age: 365 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSNO therapy<br>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. | Drug: GSNO<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Emergent Adverse Events | Occurrence of >grade 3 adverse events related to the treatment | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| S-nitrosoglutathione change | Percent change in S-nitrosoglutathione pre/post treatment | 30 minutes | 
| Change in oxygen saturation index | 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 | 4 hours | 
| Change in GSNO catabolism pre/post treatment | Percent change in GSNO catabolism pre/post treatment | 30 minutes | 
| Intermittent hypoxemia as measured by oxygen saturation post treatment | Incidence, duration, and nadirs of intermittent hypoxemia (SpO2 <80%) as measured by oxygen saturation parameters post treatment | 4 hours | 
| Ventilator parameters post treatment | Change in ventilator parameters post treatment | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bronchopulmonary dysplasia, respiratory failure