Clinical trial NCT04619602: Inhaled Treatment for Bronchopulmonary Dysplasia
Official title: Pilot Study of an Inhaled Treatment for Bronchopulmonary Dysplasia
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
Conditions: Bronchopulmonary Dysplasia
Keywords: bronchopulmonary dysplasia
respiratory failure
Lead sponsor: University Hospitals Cleveland Medical Center
Sponsor class: OTHER
First posted: 2020-11-06
Enrollment: 20
Sex: ALL
Minimum age (years): 29
Maximum age (years): 365
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 \[during administration and tracked for next 7 days\].

Eligibility criteria: 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

Primary outcomes:
measure: Treatment Emergent Adverse Events
timeFrame: 7 days
Secondary outcomes:
measure: S-nitrosoglutathione change
timeFrame: 30 minutes
measure: Change in oxygen saturation index
timeFrame: 4 hours
measure: Change in GSNO catabolism pre/post treatment
timeFrame: 30 minutes
measure: Intermittent hypoxemia as measured by oxygen saturation post treatment
timeFrame: 4 hours
measure: Ventilator parameters post treatment
timeFrame: 4 hours
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center Rainbow Babies and Children's Hospital
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center
name: Thomas Raffay, MD
role: PRINCIPAL_INVESTIGATOR
References: