KL₄Surfactant Treatment in Patients With ARDS

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).

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).

Study Overview

• Status: Terminated
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: A.1 Lucinactant; Drug: A.2 Lucinactant; Drug: A.3 Lucinactant; Drug: A.4 Lucinactant; Drug: B.1 Lucinactant; Drug: B.2 Lucinactant; Other: B.3 SoC

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.

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Warrington, Pennsylvania, United States, 18976-3646
      • Discovery Laboratories, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: A.1 Lucinactant; 3 30 mL aliquots at concentrations of 5, 5, and 10 mg/mL; Other Names: KL₄Surfactant
Experimental: 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.	Drug: A.2 Lucinactant; 3 30 mL aliquots at a concentration of 10 mg/mL each; Other Names: KL₄Surfactant
Experimental: 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.	Drug: A.3 Lucinactant; 2 50 mL aliquots at concentrations of 10 and 20 mg/mL; Other Names: KL₄Surfactant
Experimental: 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.	Drug: A.4 Lucinactant; 2 50 mL aliquots at concentrations of 10 and 20 mg/mL, with bolus re-treatment allowed; Other Names: KL₄Surfactant
Experimental: 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.	Drug: B.1 Lucinactant; 2 50 mL aliquots at concentrations of 10 and 20 mg/mL; Other Names: KL₄Surfactant
Experimental: 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.	Drug: B.2 Lucinactant; 2 50 mL aliquots at concentrations of 10 and 20 mg/mL, with bolus re-treatment allowed; Other Names: KL₄Surfactant
Other: B.3 SoC; 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; Standard ARDS management and ICU care; Other Names: Negative control

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: Windtree Therapeutics
• Investigators: Study Director: Timothy J Gregory, PhD, Windtree Therapeutics

Study record dates

Study Major Dates

• Study Start: May 1, 2001
• Primary Completion (Actual): February 1, 2006
• Study Completion (Actual): February 1, 2006

Study Registration Dates

• First Submitted: September 14, 2005
• First Submitted That Met QC Criteria: September 21, 2005
• First Posted (Estimate): September 22, 2005

Study Record Updates

• Last Update Posted (Actual): August 9, 2018
• Last Update Submitted That Met QC Criteria: July 12, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Respiratory System Agents; Pulmonary Surfactants
• Other Study ID Numbers: KL4-ARDS-04