Acute Respiratory Distress Syndrome
Conditions
Keywords
Acute Respiratory Distress Syndrome, ARDS, Nitric Oxide
Brief summary
This research project is an open-label, randomized study for the use of Nitric Oxide in pediatric patients with acute respiratory distress syndrome (ARDS). The study examines whether nitric oxide (NO) treatment impacts the the P:F ratio (arterial partial pressure of oxygen (PaO2) divided by fraction of inspired oxygen (FiO2) in patients with ARDS. The goal of the study is to evaluate whether the order of NO therapy will have any effect on response, and evaluate the characteristics of patients who respond to NO compared to those who do not.
Detailed description
At low concentrations, nitric oxide(NO) functions as a cellular messenger and regulator of microcirculation. NO may have an important role in the pathogenesis of ARDS as well as its treatment. NO may be primarily useful in improving matching of ventilation and perfusion in the lung. The aims of the study are to attempt to show that NO will improve oxygenation as evidenced by improvement in PaO2/FiO2. Secondary aims are to see if the improvement in oxygenation allows there to be decreased time on FiO2\>0.60, evaluate whether the order of NO therapy will have any effect on response, and evaluate the characteristics of patients who respond to NO compared to those who do not. Subjects will be randomized to receive either nitric oxide first (nitric oxide for the first 4 hours, then no intervention/no nitric oxide for the next 4 hours) or delayed treatment with nitric oxide (no intervention/no nitric oxide for the first 4 hours, then nitric oxide for the next 4 hours).. Blood gases were monitored once an hour during study participation (total of 8 hours). Final PaO2/FiO2 levels will be compared after 8 hours of study treatment in each group.
Interventions
DRUGNitric Oxide
Subjects will receive inhaled Nitric Oxide at a dose of 10 parts per million (ppm) for a 4 hour study period. Blood gases will be collected once an hour.
OTHERNo Intervention
Subjects will receive no intervention (i.e., no nitric oxide treatment) for a 4 hour study period. Blood gases will be collected once an hour. During this time, all subjects will receive standard clinical care.
Sponsors
Mallinckrodt
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
* Patient is intubated and mechanically ventilated in the Pediatric Intensive Care Unit with a PaO2/FiO2 ratio less than or equal to 100, FiO2 greater than or equal to 0.60, PEEP greater than or equal to 10, and a Murray score greater than or equal to 2.5.
Exclusion criteria
* Neonates (1 week to 28 days) and/or patients on extracorporeal membrane oxygenation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean PaO2/FiO2 Ratio | 8 hours | Arterial blood gas measurements with cooximetry to evaluate arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2) ratio. The mean PaO2/FiO2 ratio for each group after completion 8 hour of study participation was compared |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from the Pediatric Intensive Care Unit from 2000-2008.
Participants by arm
| Arm | Count |
|---|---|
| Nitric Oxide First Subjects received 10 ppm nitric oxide for the first 4 hours of study participation After which, the NO was turned off and subjects received no intervention (no nitric oxide) for the next 4 hours of study participation. After the initial 8 hours of study participation, subjects will remain on whichever intervention (no nitric oxide versus 10 ppm nitric oxide) they responded best to. | 24 |
| Delayed Nitric Oxide Subjects received no intervention (no nitric oxide) for the first 4 hours of study participation. After which, they received 10 ppm nitric oxide for the next 4 hours of study participation. After the initial 8 hours of study participation, subjects will remain on whichever intervention (no nitric oxide versus 10 ppm nitric oxide) they responded best to. | 28 |
| Total | 52 |
Baseline characteristics
| Characteristic | Delayed Nitric Oxide | Nitric Oxide First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 28 Participants | 24 Participants | 52 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 8.06 years STANDARD_DEVIATION 6.28 | 9.93 years STANDARD_DEVIATION 6.79 | 8.84 years STANDARD_DEVIATION 6.5 |
| Region of Enrollment United States | 28 participants | 24 participants | 52 participants |
| Sex: Female, Male Female | 14 Participants | 10 Participants | 24 Participants |
| Sex: Female, Male Male | 14 Participants | 14 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 0 / 28 |
| serious Total, serious adverse events | 0 / 24 | 0 / 28 |
Outcome results
Primary
Mean PaO2/FiO2 Ratio
Arterial blood gas measurements with cooximetry to evaluate arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2) ratio. The mean PaO2/FiO2 ratio for each group after completion 8 hour of study participation was compared
Time frame: 8 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immediate Nitric Oxide Treatment | Mean PaO2/FiO2 Ratio | 115.6 mmHg | Standard Deviation 40.6 |
| Delayed Nitric Oxide Treatment | Mean PaO2/FiO2 Ratio | 115.9 mmHg | Standard Deviation 40 |
Comparison: Differences in mean PaO2/FiO2 ratios between the two groups will help to determine whether order of therapy (immediate treatment with nitric oxide versus delayed treatment with nitric oxide) impacts outcomes.p-value: >0.05t-test, 2 sided