Clinical trial NCT04389671: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
Lead sponsor: Windtree Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-05-15
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, single treatment of reconstituted Lucinactant, delivered as an intratracheal liquid.
Primary purpose: TREATMENT

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.

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:

  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.

Primary outcomes:
measure: Oxygen Index (OI)
timeFrame: Baseline through 12 hours post initiation of dosing
Secondary outcomes:
measure: Fraction of Inspired Oxygen (FiO2)
timeFrame: Baseline through 24 hours post initiation of dosing
measure: Partial Pressure of Oxygen (PaO2)
timeFrame: Baseline through 24 hours post initiation of dosing
measure: Oxygenation From Pulse Oximetry (SpO2)
timeFrame: Baseline through 24 hours post initiation of dosing
measure: Oxygen Index (OI)
timeFrame: Baseline through 24 hours post initiation of dosing
measure: Partial Pressure of Carbon Dioxide (PaCO2)
timeFrame: Baseline through 24 hours post initiation of dosing
measure: End Tidal Carbon Dioxide (ETCO2)
timeFrame: Baseline through 24 hours post initiation of dosing
measure: PaO2 to FiO2 (P/F) Ratio
timeFrame: Baseline through 24 hours post initiation of dosing
measure: SpO2 to FiO2 (S/F) Ratio
timeFrame: Through 24 hours
measure: Plateau Pressure (PPLAT)
timeFrame: Through 24 Hours
measure: Peak Inspiratory Pressure (PIP)
timeFrame: Baseline through 24 hours post initiation of dosing
measure: Peak Expiratory End Pressure (PEEP)
timeFrame: Through 24 hours
measure: Ventilation Index (VI)
timeFrame: Baseline through 24 hours post initiation of dosing
measure: Lung Compliance (CL)
timeFrame: Baseline through 24 hours post initiation of dosing
measure: Daily Lung Compliance (Static) on Ventilator
timeFrame: Baseline through 24 hours post initiation of dosing
measure: Ventilator Free Days
timeFrame: Baseline through 30 days post initiation of dosing
measure: Days in the Intensive Care Unit (ICU)
timeFrame: Baseline through 30 days post initiation of dosing
measure: Days in the Hospital
timeFrame: Baseline through 30 days post initiation of dosing
measure: All-cause Mortality
timeFrame: Baseline through 30 days post initiation of dosing
measure: Organ Failure Free Days
timeFrame: Baseline through 30 days post initiation of dosing
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University California San Diego - Jacobs Medical Center
state: California
city: San Diego
country: United States
facility: University of California San Diego - Medical Center, Hillcrest
state: California
city: Augusta
country: United States
facility: Augusta University Health
state: Georgia
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Buenos Aires
country: Argentina
facility: Fundacion Sanatorio Güemes
city: Buenos Aires
country: Argentina
facility: Hospital Alemán
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Bueno Aires
city: Buenos Aires
country: Argentina
facility: CEMIC - Centro de Educacion Medica e Investigaciones Clinicals
Study officials:
affiliation: Duke University
name: Yuh-Chin T Huang, MD, MHS
role: PRINCIPAL_INVESTIGATOR
affiliation: Windtree Therapeutics
name: Steve G Simonson, MD
role: STUDY_DIRECTOR
References:
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.
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.