Pilot Study of an Inhaled Treatment for Bronchopulmonary Dysplasia
Trial Snapshot
- Phase
- Phase 1
- Status
- Withdrawn
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Treatment Emergent Adverse Events
Study Overview
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].
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 29 Days to 365 Days (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
GSNO therapy
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.
Intervention: GSNO (Drug)
Outcomes
Primary Outcomes
Treatment Emergent Adverse Events
Time Frame: 7 days
Occurrence of \>grade 3 adverse events related to the treatment
Secondary Outcomes
- Intermittent hypoxemia as measured by oxygen saturation post treatment(4 hours)
- Change in oxygen saturation index(4 hours)
- Change in GSNO catabolism pre/post treatment(30 minutes)
- Ventilator parameters post treatment(4 hours)
- S-nitrosoglutathione change(30 minutes)
Investigators
Thomas Michael Raffay, MD
Sponsor-Investigator
University Hospitals Cleveland Medical Center