KL₄Surfactant Treatment in Patients With ARDS

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Multicenter, Randomized, Controlled Trial Comparing the Safety and Effectiveness of SURFAXIN® (Lucinactant) Delivered Via Bronchopulmonary Segmental Lavage to Standard of Care in Patients With Acute Respiratory Distress Syndrome (ARDS).

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: A.1 Lucinactant
* Other: B.3 SoC
* Drug: A.2 Lucinactant
* Drug: A.3 Lucinactant
* Drug: A.4 Lucinactant
* Drug: B.1 Lucinactant
* Drug: B.2 Lucinactant


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A.1 Lucinactant<br>3 30-mL aliquots per bronchopulmonary segment using concentrations of 5, 5, and 10 mg/mL total phopholipids. One re-treatment at 48 hours. | Drug: A.1 Lucinactant<br>* 3 30 mL aliquots at concentrations of 5, 5, and 10 mg/mL<br>* Other names: KL₄Surfactant;|
| Experimental: A.2 Lucinactant<br>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. | Drug: A.2 Lucinactant<br>* 3 30 mL aliquots at a concentration of 10 mg/mL each<br>* Other names: KL₄Surfactant;|
| Experimental: A.3 Lucinactant<br>2 50-mL aliquots per bronchopulmonary segment using concentrations of 10 and 20 mg/mL total phospholipids. One lavage re-treatment at 48 hours. | Drug: A.3 Lucinactant<br>* 2 50 mL aliquots at concentrations of 10 and 20 mg/mL<br>* Other names: KL₄Surfactant;|
| Experimental: A.4 Lucinactant<br>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. | Drug: A.4 Lucinactant<br>* 2 50 mL aliquots at concentrations of 10 and 20 mg/mL, with bolus re-treatment allowed<br>* Other names: KL₄Surfactant;|
| Experimental: B.1 Lucinactant<br>2 50-mL aliquots per bronchopulmonary segment using concentrations of 10 and 20 mg/mL total phospholipids. One lavage re-treatment at 48 hours. | Drug: B.1 Lucinactant<br>* 2 50 mL aliquots at concentrations of 10 and 20 mg/mL<br>* Other names: KL₄Surfactant;|
| Experimental: B.2 Lucinactant<br>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. | Drug: B.2 Lucinactant<br>* 2 50 mL aliquots at concentrations of 10 and 20 mg/mL, with bolus re-treatment allowed<br>* Other names: KL₄Surfactant;|
| Other: B.3 SoC<br>Received standard ARDS management and ICU care (Standard of Care [SOC]). Included, but was not limited to, support with oxygen, conventional mechanical ventilation, sedations, and paralysis. | Other: B.3 SoC<br>* Standard ARDS management and ICU care<br>* Other names: Negative control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality |  | Through 28 days | 
| Days in ICU | Number of days in ICU | Through 28 days |