Acute Hypoxemic Respiratory Failure
Conditions
Brief summary
Treatment with lucinactant, a peptide-containing synthetic lung surfactant, will be evaluated in young children with acute respiratory failure who require mechanical ventilation (life support), to determine if it is safe and if treatment with lucinactant will reduce the number of days a child needs mechanical ventilation (life support).
Detailed description
Determine the safety and tolerability of administration of a peptide-containing synthetic lung surfactant, lucinactant, in children up to two years of age and assess whether treatment with lucinactant can decrease the duration of mechanical ventilation in young children.
Interventions
DRUGLucinactant
Slow intra-tracheal instillation
OTHERSham Comparator
Slow intra-tracheal instillation
Sponsors
Windtree Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 2 Years
Healthy volunteers
No
Inclusion criteria
* ≥ 38 weeks (corrected age) to 2 years (24 months) * Intubated and mechanically ventilated (MV) for ≥ 6 hours and anticipated need for MV for ≥ 24 hours * Persistent hypoxia * Written informed consent
Exclusion criteria
* Mechanical Ventilation for \> 48 hours * Oxygenation index ≥ 25, if arterial line was avialable * Pre-existing clinically significant or palliated/uncorrected cardiac disease adversely affecting cardiopulmonary function and gas exchange * Neuromuscular disease or hypotonia * Upper airway disease * Baseline requirment for supplemental oxygen * Untreated pneumothorax * Off-label use of commercially available surfactant outside neonatal period * History of prematurity and passive immunoprophylaxis with humanized monoclonal antibody * Head injury with Glasgow Coma Scale \< 8 * Brain death or impending brain death * Do not resuscitate orders * Cardiopulmonary resuscitation within 6 hours of meeting entry criteria * Experimental therapy in which the intervention potentially affects respiratory outcomes * Any transplant recipient * Meconium aspiration syndrome * Bordetella pertussis infection confirmed via laboratory tests and/or highly suspected pertussis infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Mechanical Ventilation Through 14 Days | Up to 14 Days | Duration of mechanical ventilation (MV) from baseline to successful extubation (not receiving MV for at least 24 hours) through a maximum of 14 days. |
Secondary
| Measure | Time frame |
|---|---|
| Ventilator-free Days; Duration of Days on Oxygen, Intensive Care Unit (ICU) Stay, and Hospitalization Through 14 Days | Up to 14 days |
Countries
Chile, United States
Participant flow
Recruitment details
Subjects were enrolled at 24 hospitals in the United States and Chile from 04 June, 2007 to 23 March, 2010. Last subject's last visit occurred on 05 April, 2010.
Participants by arm
| Arm | Count |
|---|---|
| Lucinactant KL₄Surfactant (lucinactant) endotracheal instillation | 84 |
| Sham Air Sham air (placebo) instillation | 81 |
| Total | 165 |
Baseline characteristics
| Characteristic | Lucinactant | Sham Air | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 84 Participants | 81 Participants | 165 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 | 0.44 years STANDARD_DEVIATION 0.43 | 0.45 years STANDARD_DEVIATION 0.43 | 0.45 years STANDARD_DEVIATION 0.43 |
| Region of Enrollment Chile | 56 participants | 54 participants | 110 participants |
| Region of Enrollment United States | 28 participants | 27 participants | 55 participants |
| Sex: Female, Male Female | 29 Participants | 27 Participants | 56 Participants |
| Sex: Female, Male Male | 55 Participants | 54 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 65 / 84 | 62 / 81 |
| serious Total, serious adverse events | 20 / 84 | 14 / 81 |
Outcome results
Primary
Duration of Mechanical Ventilation Through 14 Days
Duration of mechanical ventilation (MV) from baseline to successful extubation (not receiving MV for at least 24 hours) through a maximum of 14 days.
Time frame: Up to 14 Days
Population: The sample size calculation was based on historical data and expected treatment effect. The primary efficacy analysis was for the intent-to-treat population, defined as all randomized subjects (N=165). A supportive population (N=134) of subjects without a major protocol violation that could impact efficacy was also used for efficacy analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Lucinactant | Duration of Mechanical Ventilation Through 14 Days | 4.0 days |
| Sham Air | Duration of Mechanical Ventilation Through 14 Days | 4.5 days |
Secondary
Ventilator-free Days; Duration of Days on Oxygen, Intensive Care Unit (ICU) Stay, and Hospitalization Through 14 Days
Time frame: Up to 14 days
Population: The sample size calculation was based on historical data and expected treatment effect. The primary efficacy analysis was for the intent-to-treat population, defined as all randomized subjects (N=165). A supportive population (N=134) of subjects without a major protocol violation that could impact efficacy was also used for efficacy analyses.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Lucinactant | Ventilator-free Days; Duration of Days on Oxygen, Intensive Care Unit (ICU) Stay, and Hospitalization Through 14 Days | Ventilator-free days | 5.2 days |
| Lucinactant | Ventilator-free Days; Duration of Days on Oxygen, Intensive Care Unit (ICU) Stay, and Hospitalization Through 14 Days | Duration in Pediatric Intensive Care Unit (PICU) | 6.2 days |
| Lucinactant | Ventilator-free Days; Duration of Days on Oxygen, Intensive Care Unit (ICU) Stay, and Hospitalization Through 14 Days | Duration of Supplemental Oxygen | 7.7 days |
| Lucinactant | Ventilator-free Days; Duration of Days on Oxygen, Intensive Care Unit (ICU) Stay, and Hospitalization Through 14 Days | Duration of Hospitalization | 10.0 days |
| Sham Air | Ventilator-free Days; Duration of Days on Oxygen, Intensive Care Unit (ICU) Stay, and Hospitalization Through 14 Days | Duration of Hospitalization | 9.7 days |
| Sham Air | Ventilator-free Days; Duration of Days on Oxygen, Intensive Care Unit (ICU) Stay, and Hospitalization Through 14 Days | Ventilator-free days | 4.6 days |
| Sham Air | Ventilator-free Days; Duration of Days on Oxygen, Intensive Care Unit (ICU) Stay, and Hospitalization Through 14 Days | Duration of Supplemental Oxygen | 7.9 days |
| Sham Air | Ventilator-free Days; Duration of Days on Oxygen, Intensive Care Unit (ICU) Stay, and Hospitalization Through 14 Days | Duration in Pediatric Intensive Care Unit (PICU) | 6.7 days |