Inhaled Treatment for Bronchopulmonary Dysplasia

• Sponsor: University Hospitals Cleveland Medical Center (Other)
• Overall Status: Suspended
• CT.gov ID: NCT04619602
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 15
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Bronchopulmonary Dysplasia	Drug: GSNO	Phase 1

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
• Anticipated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study of an Inhaled Treatment for Bronchopulmonary Dysplasia
• Anticipated Study Start Date: Jul 1, 2023
• Anticipated Primary Completion Date: Sep 1, 2024
• Anticipated Study Completion Date: Oct 1, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Treatment Emergent Adverse Events [7 days]

   Occurrence of >grade 3 adverse events related to the treatment

Secondary Outcome Measures

1. S-nitrosoglutathione change [30 minutes]

   Percent change in S-nitrosoglutathione pre/post treatment

2. 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

3. Change in GSNO catabolism pre/post treatment [30 minutes]

   Percent change in GSNO catabolism pre/post treatment

4. 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

5. Ventilator parameters post treatment [4 hours]

   Change in ventilator parameters post treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 29 Days to 365 Days
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospitals Cleveland Medical Center Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• University Hospitals Cleveland Medical Center

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Thomas Michael Raffay, MD, Sponsor-Investigator, University Hospitals Cleveland Medical Center
• ClinicalTrials.gov Identifier: NCT04619602
• Other Study ID Numbers: BPD
• First Posted: Nov 6, 2020
• Last Update Posted: Aug 11, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Thomas Michael Raffay, MD, Sponsor-Investigator, University Hospitals Cleveland Medical Center: bronchopulmonary dysplasia; respiratory failure
• Additional relevant MeSH terms: Bronchopulmonary Dysplasia; Hyperplasia

Study Results

No Results Posted as of Aug 11, 2022