Inhaled Treatment for Bronchopulmonary Dysplasia

Phase 1

Suspended

• Conditions: Bronchopulmonary Dysplasia
• Interventions: Drug: GSNO

• Registration Number: NCT04619602
• Lead Sponsor: University Hospitals Cleveland Medical Center

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 Timeline

• Study First Submitted: 2020-11-02
• Study First Submitted QC: 2020-11-02
• Study First Posted: 2020-11-06
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-19
• Last Update Posted: 2024-08-21
• Study Start: 2025-08-01
• Primary Completion: 2025-09-01
• Study Completion: 2025-09-01

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
GSNO therapy	GSNO	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.

Primary Outcome Measures

Name	Time	Method
Treatment Emergent Adverse Events	7 days	Occurrence of \>grade 3 adverse events related to the treatment

Secondary Outcome Measures

Name	Time	Method
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
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
Ventilator parameters post treatment	4 hours	Change in ventilator parameters post treatment
S-nitrosoglutathione change	30 minutes	Percent change in S-nitrosoglutathione pre/post treatment

Trial Locations

Locations (1)

University Hospitals Cleveland Medical Center Rainbow Babies and Children's Hospital; 🇺🇸 Cleveland, Ohio, United States