Inhaled Treatment for Bronchopulmonary Dysplasia

Pilot Study of an Inhaled Treatment for Bronchopulmonary Dysplasia

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

Study Overview

• Status: Suspended
• Conditions: Bronchopulmonary Dysplasia
• Intervention / Treatment: Drug: GSNO

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 Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center Rainbow Babies and Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 1 year (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospitals Cleveland Medical Center
• Investigators: Principal Investigator: Thomas Raffay, MD, University Hospitals Cleveland Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: November 2, 2020
• First Submitted That Met QC Criteria: November 2, 2020
• First Posted (Actual): November 6, 2020

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: respiratory failure; bronchopulmonary dysplasia
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Hyperplasia; Bronchopulmonary Dysplasia
• Other Study ID Numbers: BPD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No