Inhaled Treatment for Bronchopulmonary Dysplasia
Primary Purpose
Bronchopulmonary Dysplasia
Status
Suspended
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GSNO
Sponsored by
About this trial
This is an interventional treatment trial for Bronchopulmonary Dysplasia focused on measuring bronchopulmonary dysplasia, respiratory failure
Eligibility Criteria
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
Sites / Locations
- University Hospitals Cleveland Medical Center Rainbow Babies and Children's Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
GSNO therapy
Arm Description
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.
Outcomes
Primary Outcome Measures
Treatment Emergent Adverse Events
Occurrence of >grade 3 adverse events related to the treatment
Secondary Outcome Measures
S-nitrosoglutathione change
Percent change in S-nitrosoglutathione pre/post treatment
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
Change in GSNO catabolism pre/post treatment
Percent change in GSNO catabolism pre/post treatment
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
Ventilator parameters post treatment
Change in ventilator parameters post treatment
Full Information
NCT ID
NCT04619602
First Posted
November 2, 2020
Last Updated
August 7, 2023
Sponsor
University Hospitals Cleveland Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT04619602
Brief Title
Inhaled Treatment for Bronchopulmonary Dysplasia
Official Title
Pilot Study of an Inhaled Treatment for Bronchopulmonary Dysplasia
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Suspended
Why Stopped
FDA hold
Study Start Date
August 1, 2024 (Anticipated)
Primary Completion Date
September 1, 2025 (Anticipated)
Study Completion Date
September 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospitals Cleveland Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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
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].
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchopulmonary Dysplasia
Keywords
bronchopulmonary dysplasia, respiratory failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
GSNO therapy
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
GSNO
Intervention Description
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 Measure Information:
Title
Treatment Emergent Adverse Events
Description
Occurrence of >grade 3 adverse events related to the treatment
Time Frame
7 days
Secondary Outcome Measure Information:
Title
S-nitrosoglutathione change
Description
Percent change in S-nitrosoglutathione pre/post treatment
Time Frame
30 minutes
Title
Change in oxygen saturation index
Description
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
Time Frame
4 hours
Title
Change in GSNO catabolism pre/post treatment
Description
Percent change in GSNO catabolism pre/post treatment
Time Frame
30 minutes
Title
Intermittent hypoxemia as measured by oxygen saturation post treatment
Description
Incidence, duration, and nadirs of intermittent hypoxemia (SpO2 <80%) as measured by oxygen saturation parameters post treatment
Time Frame
4 hours
Title
Ventilator parameters post treatment
Description
Change in ventilator parameters post treatment
Time Frame
4 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
29 Days
Maximum Age & Unit of Time
365 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Raffay, MD
Organizational Affiliation
University Hospitals Cleveland Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospitals Cleveland Medical Center Rainbow Babies and Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Inhaled Treatment for Bronchopulmonary Dysplasia
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