Acute Respiratory Distress Syndrome
Conditions
Brief summary
Lung wash with KL₄Surfactant of individual lung segments using a bronchoscope compared to usual care alone consisting primarily of assisted (mechanical) ventilation in patients with acute respiratory distress syndrome(ARDS).
Detailed description
This is a multinational, multicenter, two-part, Phase 2 study that will evaluate the tolerability, safety, and efficacy of KL₄Surfactant in adult ARDS patients when administered by sequential bronchoscopic lavage into each of the 19 bronchopulmonary segments of the lung and as a bolus instillation into each lung.
Interventions
DRUGA.1 Lucinactant
3 30 mL aliquots at concentrations of 5, 5, and 10 mg/mL
OTHERB.3 SoC
Standard ARDS management and ICU care
DRUGA.2 Lucinactant
3 30 mL aliquots at a concentration of 10 mg/mL each
DRUGA.3 Lucinactant
2 50 mL aliquots at concentrations of 10 and 20 mg/mL
DRUGA.4 Lucinactant
2 50 mL aliquots at concentrations of 10 and 20 mg/mL, with bolus re-treatment allowed
DRUGB.1 Lucinactant
2 50 mL aliquots at concentrations of 10 and 20 mg/mL
DRUGB.2 Lucinactant
2 50 mL aliquots at concentrations of 10 and 20 mg/mL, with bolus re-treatment allowed
Sponsors
Windtree Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Intubated and required mechanical ventilation support * Met the criteria for ARDS * Partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ≤ 200 mmHg and ≥ 60 mmHg within 60 minutes before randomization * Mean blood pressure was ≥ 60 mmHg immediately before randomization
Exclusion criteria
* Had ARDS due solely to a major trauma * Was currently participating in another clinical trial or received an experimental drug or device within the previous month * A woman of childbearing age, unless pregnancy was excluded by a negative urine hCG test or if the subject was surgically incapable of childbearing * Had a previous episode of ARDS that resolved and then recurred during the current hospitalization * Had a disease that was sufficiently advanced, in the best judgment of the Principal Investigator, to markedly limit life expectancy to \< 6 months * Was known to have AIDS or symptomatic HIV (CD4 counts \<500). Subjects with asymptomatic HIV were not excluded * Received chemotherapy or radiation within the previous 90 days * Received an organ transplant other than corneal transplants * Received, or was currently receiving, immunosuppression therapy within the last 6 months * Had severe neurological damage or the presence of a disease that was likely to significantly prevent weaning from the ventilator * Had a best Glasgow Coma Score (GCS) of ≤ 8 or an intracranial pressure ≥ 20 cm H2O prior to the institution of sedatives or paralysis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Patients Being Alive and Not Receiving Mechanical Ventilation for ≥48 Hours at the End of Day 28. | Through 28 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | Through 28 days | — |
| Days in ICU | Through 28 days | Number of days in ICU |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred between May 2001 to February 2006 in hospital ICUs
Participants by arm
| Arm | Count |
|---|---|
| A.1 Lucinactant 3 30-mL aliquots per bronchopulmonary segment using concentrations of 5, 5, and 10 mg/mL total phopholipids. One re-treatment at 48 hours. | 5 |
| A.2 Lucinactant 3 30-mL aliquots per bronchopulmonary segment using concentrations of 10, 10, and 10 mg/mL total phospholipids. One lavage re-treatment at 48 hours. | 6 |
| A.3 Lucinactant 2 50-mL aliquots per bronchopulmonary segment using concentrations of 10 and 20 mg/mL total phospholipids. One lavage re-treatment at 48 hours. | 6 |
| A.4 Lucinactant 2 50-mL aliquots per bronchopulmonary segment using concentrations of 10 and 20 mg/mL total phospholipids (TPL). One re-treatment at 48 hours. One bolus re-treatment (20 mg/mL TPL) in another 48 hours. A second bolus re-treatment (20 mg/mL TPL) administered 48 hours later. | 5 |
| B.1 Lucinactant 2 50-mL aliquots per bronchopulmonary segment using concentrations of 10 and 20 mg/mL total phospholipids. One lavage re-treatment at 48 hours. | 28 |
| B.2 Lucinactant 2 50-mL aliquots per bronchopulmonary segment using concentrations of 10 and 20 mg/mL total phospholipids (TPL). One re-treatment at 48 hours. One bolus re-treatment (20 mg/mL TPL) in another 48 hours. A second bolus re-treatment (20 mg/mL TPL) administered 48 hours later. | 38 |
| B.3 SoC Received standard ARDS management and ICU care. Included, but was not limited to, support with oxygen, conventional mechanical ventilation, sedations, and paralysis. | 36 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 2 | 1 | 2 | 6 | 0 |
Baseline characteristics
| Characteristic | A.1 Lucinactant | A.2 Lucinactant | A.3 Lucinactant | A.4 Lucinactant | B.1 Lucinactant | B.2 Lucinactant | B.3 SoC | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 6 Participants | 4 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 5 Participants | 5 Participants | 5 Participants | 26 Participants | 32 Participants | 32 Participants | 107 Participants |
| Age, Continuous | 52.7 years STANDARD_DEVIATION 24 | 50.5 years STANDARD_DEVIATION 17.1 | 45.6 years STANDARD_DEVIATION 16 | 41.6 years STANDARD_DEVIATION 6.2 | 46.3 years STANDARD_DEVIATION 12.5 | 51.8 years STANDARD_DEVIATION 13 | 47.3 years STANDARD_DEVIATION 12.6 | 48.5 years STANDARD_DEVIATION 13.1 |
| Region of Enrollment Canada | 0 participants | 0 participants | 0 participants | 0 participants | 3 participants | 5 participants | 9 participants | 17 participants |
| Region of Enrollment Russian Federation | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 4 participants | 5 participants |
| Region of Enrollment United States | 5 participants | 6 participants | 6 participants | 5 participants | 25 participants | 32 participants | 23 participants | 102 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 4 Participants | 1 Participants | 9 Participants | 22 Participants | 16 Participants | 57 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants | 4 Participants | 19 Participants | 16 Participants | 20 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 5 | 6 / 6 | 6 / 6 | 5 / 5 | 24 / 28 | 37 / 38 | 31 / 36 |
| serious Total, serious adverse events | 4 / 5 | 2 / 6 | 1 / 6 | 0 / 5 | 10 / 28 | 19 / 38 | 13 / 36 |
Outcome results
Primary
Incidence of Patients Being Alive and Not Receiving Mechanical Ventilation for ≥48 Hours at the End of Day 28.
Time frame: Through 28 days
Population: In Part A, 5 subjects provided a reasonable cohort to adequately examine the safety of each treatment regimen.~In Part B, 30 subjects were planned to be enrolled in each treatment group (a total of 90 subjects), enough to calculate the dose response curve.~Analyses conducted on Intent-to-Treat population (all enrolled subjects).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A.1 Lucinactant | Incidence of Patients Being Alive and Not Receiving Mechanical Ventilation for ≥48 Hours at the End of Day 28. | 2 participants |
| A.2 Lucinactant | Incidence of Patients Being Alive and Not Receiving Mechanical Ventilation for ≥48 Hours at the End of Day 28. | 4 participants |
| A.3 Lucinactant | Incidence of Patients Being Alive and Not Receiving Mechanical Ventilation for ≥48 Hours at the End of Day 28. | 4 participants |
| A.4 Lucinactant | Incidence of Patients Being Alive and Not Receiving Mechanical Ventilation for ≥48 Hours at the End of Day 28. | 5 participants |
| B.1 Lucinactant | Incidence of Patients Being Alive and Not Receiving Mechanical Ventilation for ≥48 Hours at the End of Day 28. | 20 participants |
| B.2 Lucinactant | Incidence of Patients Being Alive and Not Receiving Mechanical Ventilation for ≥48 Hours at the End of Day 28. | 26 participants |
| B.3 SoC | Incidence of Patients Being Alive and Not Receiving Mechanical Ventilation for ≥48 Hours at the End of Day 28. | 29 participants |
Comparison: Null hypothesis: No difference between treatment groupsp-value: 0.794Cochran-Mantel-Haenszel
Comparison: Null hypothesis: No difference between treatment groupsp-value: 0.236Cochran-Mantel-Haenszel
Comparison: Null hypothesis: No difference between treatment groupsp-value: 0.396Cochran-Mantel-Haenszel
Secondary
Days in ICU
Number of days in ICU
Time frame: Through 28 days
Population: In Part A, 5 subjects provided a reasonable cohort to adequately examine the safety of each treatment regimen.~In Part B, 30 subjects were planned to be enrolled in each treatment group (a total of 90 subjects), enough to calculate the dose response curve.~Analyses conducted on Intent-to-Treat population (all enrolled subjects).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A.1 Lucinactant | Days in ICU | 23.4 days | Standard Deviation 7.06 |
| A.2 Lucinactant | Days in ICU | 20.5 days | Standard Deviation 7.53 |
| A.3 Lucinactant | Days in ICU | 14.3 days | Standard Deviation 9.81 |
| A.4 Lucinactant | Days in ICU | 20.0 days | Standard Deviation 2.74 |
| B.1 Lucinactant | Days in ICU | 15.3 days | Standard Deviation 9.01 |
| B.2 Lucinactant | Days in ICU | 19.9 days | Standard Deviation 7.66 |
| B.3 SoC | Days in ICU | 17.4 days | Standard Deviation 8.1 |
p-value: 0.028ANOVA
p-value: 0.147ANOVA
p-value: 0.293ANOVA
Secondary
Mortality
Time frame: Through 28 days
Population: In Part A, 5 subjects provided a reasonable cohort to adequately examine the safety of each treatment regimen.~In Part B, 30 subjects were planned to be enrolled in each treatment group (a total of 90 subjects), enough to calculate the dose response curve.~Analyses conducted on Intent-to-Treat population (all enrolled subjects).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A.1 Lucinactant | Mortality | 3 participants |
| A.2 Lucinactant | Mortality | 2 participants |
| A.3 Lucinactant | Mortality | 0 participants |
| A.4 Lucinactant | Mortality | 0 participants |
| B.1 Lucinactant | Mortality | 4 participants |
| B.2 Lucinactant | Mortality | 9 participants |
| B.3 SoC | Mortality | 5 participants |
p-value: 0.346Cochran-Mantel-Haenszel
p-value: 0.286Cochran-Mantel-Haenszel
p-value: 0.964Cochran-Mantel-Haenszel