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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04389671
• Other study ID #: 02-CL-2001a
• Status: Completed
• Phase: Phase 2
• Start date: January 5, 2021
• Est. completion date: February 20, 2022

Study information

• Verified date: June 2023
• Source: Windtree Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 20, 2022
• Est. primary completion date: February 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
• COVID-19
• Lung Injury
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn

Intervention

Drug:
• Lucinactant
Lucinactant administered as a liquid at a dose of 80 mg total phospholipids (TPL)/kg lean body weight delivered

Locations

Country	Name	City	State
Argentina	CEMIC - Centro de Educacion Medica e Investigaciones Clinicals	Buenos Aires
Argentina	Fundacion Sanatorio Güemes	Buenos Aires
Argentina	Hospital Alemán	Buenos Aires
Argentina	Hospital Italiano de Bueno Aires	Buenos Aires
United States	Augusta University Health	Augusta	Georgia
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Duke University Medical Center	Durham	North Carolina
United States	University California San Diego - Jacobs Medical Center	La Jolla	California
United States	University of Kentucky	Lexington	Kentucky
United States	University of California San Diego - Medical Center, Hillcrest	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Windtree Therapeutics

Countries where clinical trial is conducted

United States,  Argentina, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline through 12 hours post initiation of dosing
Secondary	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%)	Baseline through 24 hours post initiation of dosing
Secondary	Partial Pressure of Oxygen (PaO2)	Change from baseline in PaO2 measured using mean and standard deviation	Baseline through 24 hours post initiation of dosing
Secondary	Oxygenation From Pulse Oximetry (SpO2)	Change from baseline in SpO2 measured using mean and standard deviation	Baseline through 24 hours post initiation of dosing
Secondary	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.	Baseline through 24 hours post initiation of dosing
Secondary	Partial Pressure of Carbon Dioxide (PaCO2)	Change from baseline in PaCO2 measured using mean and standard deviation	Baseline through 24 hours post initiation of dosing
Secondary	End Tidal Carbon Dioxide (ETCO2)	Change from baseline in ETCO2 measured using mean and standard deviation	Baseline through 24 hours post initiation of dosing
Secondary	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.	Baseline through 24 hours post initiation of dosing
Secondary	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.	Through 24 hours
Secondary	Plateau Pressure (PPLAT)	Change from baseline in PPLAT, as measured on the ventilator, measured using mean and standard deviation.	Through 24 Hours
Secondary	Peak Inspiratory Pressure (PIP)	Change from baseline in PIP, as measured on the ventilator, measured using mean and standard deviation.	Baseline through 24 hours post initiation of dosing
Secondary	Peak Expiratory End Pressure (PEEP)	Change from baseline in PEEP, measured using mean and standard deviation.	Through 24 hours
Secondary	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.	Baseline through 24 hours post initiation of dosing
Secondary	Lung Compliance (CL)	Change from baseline in lung compliance measured using measured using mean and standard deviation.	Baseline through 24 hours post initiation of dosing
Secondary	Daily Lung Compliance (Static) on Ventilator	Change from baseline in daily lung compliance (static) on ventilator using measured using mean and standard deviation.	Baseline through 24 hours post initiation of dosing
Secondary	Ventilator Free Days	Ventilator free days measured using mean and standard deviation.	Baseline through 30 days post initiation of dosing
Secondary	Days in the Intensive Care Unit (ICU)	Days in the intensive care unit (ICU) measured using mean and standard deviation.	Baseline through 30 days post initiation of dosing
Secondary	Days in the Hospital	Days in the hospital measured using mean and standard deviation.	Baseline through 30 days post initiation of dosing
Secondary	All-cause Mortality	Number of participant deaths.	Baseline through 30 days post initiation of dosing
Secondary	Organ Failure Free Days	Organ failure free days measured using mean and standard deviation.	Baseline through 30 days post initiation of dosing