Back to resultsThe Safety and Preliminary Tolerability of Lyophilized Lucinactant in Adults With Coronavirus Disease 2019 (COVID-19)
Primary Purpose
COVID-19, Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Lucinactant
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19
Eligibility Criteria
Inclusion Criteria:
- Signed and dated informed consent form (ICF) by the subject or legally authorized representative;
- Age 18-75 (inclusive);
- Assay positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus, preferably by polymerase chain reaction (PCR);
- Endotracheal intubation and mechanical ventilation (MV), within 7 days of initial intubation;
- In-dwelling arterial line;
- P/F ratio < 300;
- Mean blood pressure ≥ 65 mmHg, immediately before enrollment;
- Bilateral infiltrates seen on frontal chest radiograph.
Exclusion Criteria:
- Life expectancy < 48 hours or do not resuscitate orders;
- Severe lung disease (home O2, forced expiratory volume at one second [FEV1] < 2 liters) not likely to respond to therapy or profound hypoxemia (ie, OI ≥ 25 or P/F < 100);
- Severe renal impairment (creatinine clearance < 30 mL/min);
- Within the last 6 months has received, or is currently receiving, immunosuppression therapy (azathioprine, cyclophosphamide or methotrexate) or any transplant recipient;
Clinically significant cardiac disease that adversely effects cardiopulmonary function:
- Acute coronary syndromes or active ischemic heart disease (as assessed by the PI using troponin and ECG)
- Cardiac ejection fraction < 40% (if known);
- Need for multiple-dose vasopressors to support blood pressure (single dose vasopressors, such as Levophed™ ≤ 0.1 mcg/kg/min are allowed);
- Cardiogenic pulmonary edema as the etiology of the current respiratory distress;
- Evidence of myocarditis or pericarditis;
- Neuromuscular disease;
- Neutropenia (ANC < 1000);
- Active malignancy that impacts treatment decisions or life expectancy related to the trial;
- Suspected concomitant bacterial or other viral lung infection. Bacterial infection defined as white blood count (WBC) > 15k and positive blood/urine/sputum culture results within 72 hours.
Sites / Locations
- University California San Diego - Jacobs Medical Center
- University of California San Diego - Medical Center, Hillcrest
- Augusta University Health
- University of Kentucky
- Tufts Medical Center
- Brigham and Women's Hospital
- Duke University Medical Center
- Fundacion Sanatorio Güemes
- Hospital Alemán
- Hospital Italiano de Bueno Aires
- CEMIC - Centro de Educacion Medica e Investigaciones Clinicals
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Lyophilized Lucinactant
Arm Description
Lyophilized Lucinactant reconstituted with sterile water for injection
Outcomes
Primary Outcome Measures
Oxygen Index (OI)
Change from baseline in OI. OI is an index value, calculated as (Mean Airway Pressure [Paw]) x (Fraction of Inspired Oxygen [FiO2]) x (100) / (Partial Pressure of Oxygen [PaO2]) measured using mean and standard deviation.
It is a calculation that measures the fraction of inspired oxygen and its usage within the body, and a lower value is better. Values can range from 0 to 1000; values under 25 are correspond with a good outcome.
Secondary Outcome Measures
Fraction of Inspired Oxygen (FiO2)
Change from baseline in FiO2 measured using mean and standard deviation. FiO2 level, ranging from 0.21 (room air) to 1.00 (i.e., 21% to 100%)
Partial Pressure of Oxygen (PaO2)
Change from baseline in PaO2 measured using mean and standard deviation
Oxygenation From Pulse Oximetry (SpO2)
Change from baseline in SpO2 measured using mean and standard deviation
Oxygen Index (OI)
Change from baseline in OI. OI is an index value, calculated as Paw x FiO2 x 100 / PaO2, measured using mean and standard deviation.
It is a calculation that measures the fraction of inspired oxygen and its usage within the body, and a lower value is better. Values can range from 0 to 1000; values under 25 are correspond with a good outcome.
Partial Pressure of Carbon Dioxide (PaCO2)
Change from baseline in PaCO2 measured using mean and standard deviation
End Tidal Carbon Dioxide (ETCO2)
Change from baseline in ETCO2 measured using mean and standard deviation
PaO2 to FiO2 (P/F) Ratio
Change from baseline in ratio of arterial oxygen concentration to fraction of inspired oxygen (P/F ratio) and/or ratio of pulse oximetric saturation to fraction of inspired oxygen (P/F and/or S/F ratios) measured using mean and standard deviation.
SpO2 to FiO2 (S/F) Ratio
Change from baseline in ratio of pulse oximetric saturation to fraction of inspired oxygen (S/F ratio) measured using mean and standard deviation.
Plateau Pressure (PPLAT)
Change from baseline in PPLAT, as measured on the ventilator, measured using mean and standard deviation.
Peak Inspiratory Pressure (PIP)
Change from baseline in PIP, as measured on the ventilator, measured using mean and standard deviation.
Peak Expiratory End Pressure (PEEP)
Change from baseline in PEEP, measured using mean and standard deviation.
Ventilation Index (VI)
Change from baseline in VI, defined as (Respiration Rate [RR]) × (Peak Inspiratory Pressure [PIP] - Positive End Expiratory Pressure [PEEP]) × (Partial Pressure of Arterial Carbon Dioxide (PaCO2)] / (1000), measured using mean and standard deviation. The VI is used to determine the severity of respiratory illness, with higher values indicating worsening respiratory illness.
Lung Compliance (CL)
Change from baseline in lung compliance measured using measured using mean and standard deviation.
Daily Lung Compliance (Static) on Ventilator
Change from baseline in daily lung compliance (static) on ventilator using measured using mean and standard deviation.
Ventilator Free Days
Ventilator free days measured using mean and standard deviation.
Days in the Intensive Care Unit (ICU)
Days in the intensive care unit (ICU) measured using mean and standard deviation.
Days in the Hospital
Days in the hospital measured using mean and standard deviation.
All-cause Mortality
Number of participant deaths.
Organ Failure Free Days
Organ failure free days measured using mean and standard deviation.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04389671
Brief Title
The Safety and Preliminary Tolerability of Lyophilized Lucinactant in Adults With Coronavirus Disease 2019 (COVID-19)
Official Title
A Multicenter, Single-Treatment Study to Assess the Safety and Tolerability of Lyophilized Lucinactant in Adults With COVID-19 Associated Acute Lung Injury
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
January 5, 2021 (Actual)
Primary Completion Date
February 20, 2022 (Actual)
Study Completion Date
February 20, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Windtree Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a multicenter, single-treatment study. Subjects will consist of adults with COVID-19 associated acute lung injury who are being cared for in a critical care environment.
Detailed Description
This is a multicenter, single-treatment study. Subjects will consist of adults with COVID-19 associated acute lung injury who are being cared for in a critical care environment.
Lucinactant is a synthetic surfactant that, in its liquid form (SURFAXIN®), is approved by the United States Food and Drug Administration (NDA 021746) for the prevention of respiratory distress syndrome (RDS) in premature infants at high risk for RDS.
It has been studied in over 2000 children and adults. Preliminary data from animal and adult human studies indicate that lucinactant may be able to benefit those with acute respiratory distress syndrome (ARDS) in the context of COVID-19 infection, improving oxygenation and lung compliance. When given to intubated patients, Lucinactant could potentially decrease the duration of ventilation.
Lucinactant has an extensive safety profile in different patient populations for different indications.
It is hypothesized that lucinactant may improve the respiratory status of patients suffering from COVID-19.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open-label, single treatment of reconstituted Lucinactant, delivered as an intratracheal liquid.
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lyophilized Lucinactant
Arm Type
Experimental
Arm Description
Lyophilized Lucinactant reconstituted with sterile water for injection
Intervention Type
Drug
Intervention Name(s)
Lucinactant
Other Intervention Name(s)
Sinapultide (KL4) Surfactant
Intervention Description
Lucinactant administered as a liquid at a dose of 80 mg total phospholipids (TPL)/kg lean body weight delivered
Primary Outcome Measure Information:
Title
Oxygen Index (OI)
Description
Change from baseline in OI. OI is an index value, calculated as (Mean Airway Pressure [Paw]) x (Fraction of Inspired Oxygen [FiO2]) x (100) / (Partial Pressure of Oxygen [PaO2]) measured using mean and standard deviation.
It is a calculation that measures the fraction of inspired oxygen and its usage within the body, and a lower value is better. Values can range from 0 to 1000; values under 25 are correspond with a good outcome.
Time Frame
Baseline through 12 hours post initiation of dosing
Secondary Outcome Measure Information:
Title
Fraction of Inspired Oxygen (FiO2)
Description
Change from baseline in FiO2 measured using mean and standard deviation. FiO2 level, ranging from 0.21 (room air) to 1.00 (i.e., 21% to 100%)
Time Frame
Baseline through 24 hours post initiation of dosing
Title
Partial Pressure of Oxygen (PaO2)
Description
Change from baseline in PaO2 measured using mean and standard deviation
Time Frame
Baseline through 24 hours post initiation of dosing
Title
Oxygenation From Pulse Oximetry (SpO2)
Description
Change from baseline in SpO2 measured using mean and standard deviation
Time Frame
Baseline through 24 hours post initiation of dosing
Title
Oxygen Index (OI)
Description
Change from baseline in OI. OI is an index value, calculated as Paw x FiO2 x 100 / PaO2, measured using mean and standard deviation.
It is a calculation that measures the fraction of inspired oxygen and its usage within the body, and a lower value is better. Values can range from 0 to 1000; values under 25 are correspond with a good outcome.
Time Frame
Baseline through 24 hours post initiation of dosing
Title
Partial Pressure of Carbon Dioxide (PaCO2)
Description
Change from baseline in PaCO2 measured using mean and standard deviation
Time Frame
Baseline through 24 hours post initiation of dosing
Title
End Tidal Carbon Dioxide (ETCO2)
Description
Change from baseline in ETCO2 measured using mean and standard deviation
Time Frame
Baseline through 24 hours post initiation of dosing
Title
PaO2 to FiO2 (P/F) Ratio
Description
Change from baseline in ratio of arterial oxygen concentration to fraction of inspired oxygen (P/F ratio) and/or ratio of pulse oximetric saturation to fraction of inspired oxygen (P/F and/or S/F ratios) measured using mean and standard deviation.
Time Frame
Baseline through 24 hours post initiation of dosing
Title
SpO2 to FiO2 (S/F) Ratio
Description
Change from baseline in ratio of pulse oximetric saturation to fraction of inspired oxygen (S/F ratio) measured using mean and standard deviation.
Time Frame
Through 24 hours
Title
Plateau Pressure (PPLAT)
Description
Change from baseline in PPLAT, as measured on the ventilator, measured using mean and standard deviation.
Time Frame
Through 24 Hours
Title
Peak Inspiratory Pressure (PIP)
Description
Change from baseline in PIP, as measured on the ventilator, measured using mean and standard deviation.
Time Frame
Baseline through 24 hours post initiation of dosing
Title
Peak Expiratory End Pressure (PEEP)
Description
Change from baseline in PEEP, measured using mean and standard deviation.
Time Frame
Through 24 hours
Title
Ventilation Index (VI)
Description
Change from baseline in VI, defined as (Respiration Rate [RR]) × (Peak Inspiratory Pressure [PIP] - Positive End Expiratory Pressure [PEEP]) × (Partial Pressure of Arterial Carbon Dioxide (PaCO2)] / (1000), measured using mean and standard deviation. The VI is used to determine the severity of respiratory illness, with higher values indicating worsening respiratory illness.
Time Frame
Baseline through 24 hours post initiation of dosing
Title
Lung Compliance (CL)
Description
Change from baseline in lung compliance measured using measured using mean and standard deviation.
Time Frame
Baseline through 24 hours post initiation of dosing
Title
Daily Lung Compliance (Static) on Ventilator
Description
Change from baseline in daily lung compliance (static) on ventilator using measured using mean and standard deviation.
Time Frame
Baseline through 24 hours post initiation of dosing
Title
Ventilator Free Days
Description
Ventilator free days measured using mean and standard deviation.
Time Frame
Baseline through 30 days post initiation of dosing
Title
Days in the Intensive Care Unit (ICU)
Description
Days in the intensive care unit (ICU) measured using mean and standard deviation.
Time Frame
Baseline through 30 days post initiation of dosing
Title
Days in the Hospital
Description
Days in the hospital measured using mean and standard deviation.
Time Frame
Baseline through 30 days post initiation of dosing
Title
All-cause Mortality
Description
Number of participant deaths.
Time Frame
Baseline through 30 days post initiation of dosing
Title
Organ Failure Free Days
Description
Organ failure free days measured using mean and standard deviation.
Time Frame
Baseline through 30 days post initiation of dosing
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed and dated informed consent form (ICF) by the subject or legally authorized representative;
Age 18-75 (inclusive);
Assay positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus, preferably by polymerase chain reaction (PCR);
Endotracheal intubation and mechanical ventilation (MV), within 7 days of initial intubation;
In-dwelling arterial line;
PaO2/FiO2 (P/F) ratio < 300;
Mean blood pressure ≥ 65 mmHg, immediately before enrollment;
Bilateral infiltrates seen on frontal chest radiograph.
Exclusion Criteria:
Life expectancy < 48 hours or do not resuscitate orders;
Severe lung disease (home O2, forced expiratory volume at one second [FEV1] < 2 liters) not likely to respond to therapy or profound hypoxemia (ie, oxygen index [OI] ≥ 25 or P/F ratio < 100);
Severe renal impairment (creatinine clearance < 30 mL/min);
Within the last 6 months has received, or is currently receiving, immunosuppression therapy (azathioprine, cyclophosphamide or methotrexate) or any transplant recipient;
Clinically significant cardiac disease that adversely effects cardiopulmonary function:
Acute coronary syndromes or active ischemic heart disease (as assessed by the PI using troponin and ECG)
Cardiac ejection fraction < 40% (if known);
Need for multiple-dose vasopressors to support blood pressure (single dose vasopressors, such as Levophed™ ≤ 0.1 mcg/kg/min are allowed);
Cardiogenic pulmonary edema as the etiology of the current respiratory distress;
Evidence of myocarditis or pericarditis;
Neuromuscular disease;
Neutropenia (ANC < 1000);
Active malignancy that impacts treatment decisions or life expectancy related to the trial;
Suspected concomitant bacterial or other viral lung infection. Bacterial infection defined as white blood count (WBC) > 15k and positive blood/urine/sputum culture results within 72 hours.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yuh-Chin T Huang, MD, MHS
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Steve G Simonson, MD
Organizational Affiliation
Windtree Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
University California San Diego - Jacobs Medical Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
University of California San Diego - Medical Center, Hillcrest
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Augusta University Health
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Fundacion Sanatorio Güemes
City
Buenos Aires
ZIP/Postal Code
C1118
Country
Argentina
Facility Name
Hospital Alemán
City
Buenos Aires
ZIP/Postal Code
C1118
Country
Argentina
Facility Name
Hospital Italiano de Bueno Aires
City
Buenos Aires
ZIP/Postal Code
C119ABB
Country
Argentina
Facility Name
CEMIC - Centro de Educacion Medica e Investigaciones Clinicals
City
Buenos Aires
Country
Argentina
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
The preparation and submittal for publication of a manuscript containing the study results shall be in accordance with a process determined by a mutual written agreement among Windtree and participating institutions.
The publication or presentation of any study results shall comply with all applicable privacy laws, including but not limited to HIPAA. This trial will be registered at ClinicalTrials.gov, and results information from this trial will be submitted. In addition, every attempt will be made to publish results in peer-reviewed journals.
Citations:
PubMed Identifier
35474746
Citation
Lee CK, Merriam LT, Pearson JC, Lipnick MS, McKleroy W, Kim EY. Treating COVID-19: Evolving approaches to evidence in a pandemic. Cell Rep Med. 2022 Feb 9;3(3):100533. doi: 10.1016/j.xcrm.2022.100533. eCollection 2022 Mar 15.
Results Reference
derived
PubMed Identifier
34337553
Citation
Cohen CL, Walker KH, Hsiang M, Sonenthal PD, Riviello ED, Rouhani SA, Lipnick MS, Merriam LT, Kim EY. Combating information chaos: a case for collaborative clinical guidelines in a pandemic. Cell Rep Med. 2021 Aug 17;2(8):100375. doi: 10.1016/j.xcrm.2021.100375. Epub 2021 Jul 27.
Results Reference
derived
Learn more about this trial
The Safety and Preliminary Tolerability of Lyophilized Lucinactant in Adults With Coronavirus Disease 2019 (COVID-19)
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