The Safety and Preliminary Tolerability of Lyophilized Lucinactant in Adults With Coronavirus Disease 2019 (COVID-19)

Phase 2

Completed

• Conditions: Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS); COVID-19
• Interventions: Drug: Lucinactant

• Registration Number: NCT04389671
• Lead Sponsor: Windtree Therapeutics

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.

Study Timeline

• Study First Submitted: 2020-05-13
• Study First Submitted QC: 2020-05-13
• Study First Posted: 2020-05-15
• Study Start: 2021-01-05
• Primary Completion: 2022-02-20
• Study Completion: 2022-02-20
• Results First Submitted: 2023-02-01
• Status Verified: 2023-06
• Results First Submitted QC: 2023-06-22
• Last Update Submitted: 2023-06-22
• Results First Posted: 2023-06-23
• Last Update Posted: 2023-06-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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:

  1. Acute coronary syndromes or active ischemic heart disease (as assessed by the PI using troponin and ECG)
  2. Cardiac ejection fraction < 40% (if known);
  3. Need for multiple-dose vasopressors to support blood pressure (single dose vasopressors, such as Levophed™ ≤ 0.1 mcg/kg/min are allowed);
  4. Cardiogenic pulmonary edema as the etiology of the current respiratory distress;
  5. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lyophilized Lucinactant	Lucinactant	Lyophilized Lucinactant reconstituted with sterile water for injection

Primary Outcome Measures

Name	Time	Method
Oxygen Index (OI)	Baseline through 12 hours post initiation of dosing	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

Name	Time	Method
Fraction of Inspired Oxygen (FiO2)	Baseline through 24 hours post initiation of dosing	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%)
Peak Expiratory End Pressure (PEEP)	Through 24 hours	Change from baseline in PEEP, measured using mean and standard deviation.
Daily Lung Compliance (Static) on Ventilator	Baseline through 24 hours post initiation of dosing	Change from baseline in daily lung compliance (static) on ventilator using measured using mean and standard deviation.
Oxygenation From Pulse Oximetry (SpO2)	Baseline through 24 hours post initiation of dosing	Change from baseline in SpO2 measured using mean and standard deviation
End Tidal Carbon Dioxide (ETCO2)	Baseline through 24 hours post initiation of dosing	Change from baseline in ETCO2 measured using mean and standard deviation
Days in the Hospital	Baseline through 30 days post initiation of dosing	Days in the hospital measured using mean and standard deviation.
Oxygen Index (OI)	Baseline through 24 hours post initiation of dosing	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)	Baseline through 24 hours post initiation of dosing	Change from baseline in PaCO2 measured using mean and standard deviation
Partial Pressure of Oxygen (PaO2)	Baseline through 24 hours post initiation of dosing	Change from baseline in PaO2 measured using mean and standard deviation
PaO2 to FiO2 (P/F) Ratio	Baseline through 24 hours post initiation of dosing	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	Through 24 hours	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)	Through 24 Hours	Change from baseline in PPLAT, as measured on the ventilator, measured using mean and standard deviation.
Ventilator Free Days	Baseline through 30 days post initiation of dosing	Ventilator free days measured using mean and standard deviation.
Days in the Intensive Care Unit (ICU)	Baseline through 30 days post initiation of dosing	Days in the intensive care unit (ICU) measured using mean and standard deviation.
All-cause Mortality	Baseline through 30 days post initiation of dosing	Number of participant deaths.
Peak Inspiratory Pressure (PIP)	Baseline through 24 hours post initiation of dosing	Change from baseline in PIP, as measured on the ventilator, measured using mean and standard deviation.
Ventilation Index (VI)	Baseline through 24 hours post initiation of dosing	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)	Baseline through 24 hours post initiation of dosing	Change from baseline in lung compliance measured using measured using mean and standard deviation.
Organ Failure Free Days	Baseline through 30 days post initiation of dosing	Organ failure free days measured using mean and standard deviation.

Trial Locations

Locations (11)

Augusta University Health; 🇺🇸 Augusta, Georgia, United States

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States

Hospital Alemán; 🇦🇷 Buenos Aires, Argentina

Fundacion Sanatorio Güemes; 🇦🇷 Buenos Aires, Argentina

University of California San Diego - Medical Center, Hillcrest; 🇺🇸 San Diego, California, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

University California San Diego - Jacobs Medical Center; 🇺🇸 La Jolla, California, United States

Hospital Italiano de Bueno Aires; 🇦🇷 Buenos Aires, Argentina

CEMIC - Centro de Educacion Medica e Investigaciones Clinicals; 🇦🇷 Buenos Aires, Argentina

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States