ARDS, HumanPhase 1/2LESSCOVIDNCT04375735
London's Exogenous Surfactant Study for COVID19
A Phase 1/2 study testing Bovine Lipid Extract Surfactant in people with ARDS, Human and COVID-19, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 2 sites in Canada.
Trial summary
The research team is investigating administering exogenous surfactant in COVID-19 patients with ARDS. The overall goal is to improve the outcome (mortality) of mechanically ventilated COVID-19 patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ARDS, Human, COVID-19
- What is being tested?
- Bovine Lipid Extract Surfactant
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesCanada
- Study dates
- 23 Nov 2020to 6 Oct 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age over 18 years
- definitive proof of COVID-19 infection within 48 hours of intubation
- acute respiratory failure with PaO2/FiO2 < 300 requiring intubation
Who cannot join
- known or high suspicion of pre-existing heart failure, unstable angina
- presence of severe shock with hemodynamic instability despite escalating vasopressors
- severe, underlying lung disease (COPD, pulmonary fibrosis, lung cancer. etc.)
- Concurrent treatments are delivered directly into the lung (ie anesthetics etc)
- Diagnosis of pulmonary hemorrhage
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
London Health Sciences Centre - University Hospital
London, Ontario, N6A 5A5
Victoria Hospital
London, Ontario
About this study
Official title: Phase I/II Trial: Exogenous Surfactant Administration for Patients With COVID-19
The research team is investigating administering exogenous surfactant in COVID-19 patients with ARDS. The overall goal is to improve the outcome (mortality) of mechanically ventilated COVID-19 patients. Although the investigators anticipate that clinical outcomes may improve in the small group of patients receiving exogenous surfactant therapy in this small, single center study, the primary goal is to first determine feasibility and safety.
Read the detailed description
The most severe patients infected by the virus that causes COVID-19 develop severe respiratory failure (called ARDS) and require mechanical ventilation in the intensive care unit to help maintain oxygen delivery to the blood. Often these patients further deteriorate while on mechanical ventilation. This trial will determine the feasibility and safety of a therapy that can potentially improve lung function, reduce the need for mechanical ventilation and hopefully impact mortality.
Adult patients with COVID-19 induced respiratory failure will be randomly assigned to receive either standard treatment or standard treatment plus exogenous surfactant. If enrolled in the latter, exogenous surfactant will be instilled into the lungs within 48 hours of intubation.
The study is founded on extensive research on ARDS for over 30 years, leading to evidence suggesting that exogenous surfactant administration may be beneficial in this disease. Importantly, exogenous surfactant is already utilized all over the world to reduce mortality in preterm infants. When tested in adults with ARDS, it was shown to be well tolerated and safe. Furthermore, clinical and laboratory evidence suggests that this therapy may be most effective in patients with a direct lung infection, and when administered shortly after the patient is intubated. In this study, twenty patients who are proven COVID-19 positive and require MV due to progressive respiratory failure will be randomized to receive either 1) exogenous surfactant (BLES) as soon as possible and within 48 hours of intubation and stabilization, or 2) treatment as usual (will not be treated with surfactant). The overall goal is to improve the outcome (mortality) of mechanically ventilated COVID-19 patients. Although the investigators anticipate that clinical outcomes may improve in the small group of patients receiving exogenous surfactant therapy in this small, single center study, the primary goal is to first determine feasibility and safety. Should the investigators obtain promising results, the data obtained from this study will be used to develop a large trial to test the impact of this therapy on the clinical outcomes, including mortality, associated with COVID-19.
- Conditions
- ARDS, Human, COVID-19
- Being tested
- Bovine Lipid Extract Surfactant
- Medical subject headings
- Respiratory Distress Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bovine Lipid Extract SurfactantDrug
Also called BLES, Lung Surfactant, Bovine
BLES will be administered in doses of 50mg/kg ideal bodyweight, at a concentration of 27mg/ml so a total volume of approximately 2ml/kg will be administered. The material will be instilled via the suction catheter through the ET tube so that the ventilation circuit is not broken. Half of the material will be instilled with the patient positioned on their left and right sides, with a pause to allow 5 min of MV between. The procedure will be repeated at, 24 and 48 hours while intubated, so the patient will receive up to 3 doses. To minimize aerosol generation, all patients will be paralyzed during surfactant administration and the ventilator will be paused. The proposed administration technique, surfactant concentration, volume and dosing schedule is based on previous studies, and has shown to be safe in patients with ARDS.
| Study group | Role | What they receive |
|---|---|---|
| BLES treatment | Experimental | For patients randomized to the treatment arm, exogenous BLES will be administered as soon as possible and within 48 hours of intubation. BLES will be administered daily for up to 3 doses, or until the patient is liberated from the ventilator. Receives: Drug: Bovine Lipid Extract Surfactant |
| Control | No intervention | Patients will receive standard treatment and will not receive surfactant. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events (patient) - Decrease in oxygenation
Count of any decreases in oxygenation, expressed as PaO2 (mmHg) / FiO2 (% oxygen as a decimal), of greater than 20% during the BLES treatment and up to 30 minutes post-treatment. Change will be calculated relative to pre-treatment values.
Measured: 3 days post-randomization
Adverse events (patient) - Decrease in hemodynamics
Count of any decrease in mean arterial blood pressure >10 mmHg or requirement for >20% increase in vasopressor dose during the BLES procedure and up to 30 minutes post-treatment. Change will be calculated relative to the pre-treatment values.
Measured: 3 days post-randomization
Adverse event (healthcare worker) - Circuit breach
Number of circuit breaches. Count of any circuit breach immediately prior to and during each BLES treatment procedure will be recorded.
Measured: 3 days post-randomization
Adverse event (healthcare worker) - COVID-19 symptoms
Count of healthcare personnel involved in the BLES procedure developing symptoms and testing positive for COVID-19.
Measured: 2 weeks post-randomization
Secondary outcomes (16)
Change in oxygenation
PaO2 (in mmHg) / FiO2 (percentage oxygen expressed as a decimal) ratios captured from clinical chart
Measured: Every 12 hours post-randomization until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days.
Change in Lung compliance
Lung compliance captured from the ventilators, expressed in mL/cm H2O.
Measured: Every 12 hours post-randomization until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days.
Ventilated days
The number of days the patient is receiving mechanical ventilation.
Measured: From ICU admission until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days
Length of ICU stay
The number of days the patient is admitted to the ICU
Measured: From ICU admission until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days
Length of hospital stay
The number of days the patient is admitted to the hospital
Measured: From hospital admission until hospital discharge or death, whichever comes first, assessed up to 60 days
Mortality
Number of patients who die within 30 days of ICU admission
Measured: 30 days
G-CSF levels (serum inflammatory biomarker)
G-CSF, in pg/mL, from multiplex cytokine arrays
Measured: ICU day 0, 1, 3 and 7 (7 days)
GM-CSF levels (serum inflammatory biomarker)
GM-CSF, in pg/mL, from multiplex cytokine arrays
Measured: ICU day 0, 1, 3 and 7 (7 days)
IFN gamma levels (serum inflammatory biomarker)
IFN gamma, in pg/mL, from multiplex cytokine arrays
Measured: ICU day 0, 1, 3 and 7 (7 days)
IL-1 beta levels (serum inflammatory biomarker)
IL-1 beta, in pg/mL, from multiplex cytokine arrays
Measured: ICU day 0, 1, 3 and 7 (7 days)
IL-4 levels (serum inflammatory biomarker)
IL-4, in pg/mL, from multiplex cytokine arrays
Measured: ICU day 0, 1, 3 and 7 (7 days)
IL-6 levels (serum inflammatory biomarker)
IL-6, in pg/mL, from multiplex cytokine arrays
Measured: ICU day 0, 1, 3 and 7 (7 days)
IL-10 levels (serum inflammatory biomarker)
IL-10, in pg/mL, from multiplex cytokine arrays
Measured: ICU day 0, 1, 3 and 7 (7 days)
I levels (serum inflammatory biomarker)
I, in pg/mL, from multiplex cytokine arrays
Measured: ICU day 0, 1, 3 and 7 (7 days)
MCP-1 levels (serum inflammatory biomarker)
MCP-1, in pg/mL, from multiplex cytokine arrays
Measured: ICU day 0, 1, 3 and 7 (7 days)
TNF alpha levels (serum inflammatory biomarker)
TNF alpha, in pg/mL, from multiplex cytokine arrays
Measured: ICU day 0, 1, 3 and 7 (7 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2020
- Study start23 Nov 2020
- Primary completion1 Sep 2021
- Study completion6 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ARDS, HumanStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomly assigned to either receive exogenous surfactant daily for 3 days, or receive standard treatment.
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Collaborators
- London Health Sciences Centre
- Responsible party
- Sponsor
- Investigators
- Jim Lewis, MD, Principal investigator, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04375735
- Sponsor's protocol ID
- 9890
- Acronym
- LESSCOVID
- Status last verified
- Nov 2021
- First submitted
- 22 Apr 2020
- Last updated
- 11 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial: Exogenous Surfactant Administration for Patients With COVID-19
- ClinicalTrials.gov ID
- NCT04375735
- Acronym / sponsor ID
- LESSCOVID / 9890
- Conditions
- ARDS, Human, COVID-19
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Collaborators
- London Health Sciences Centre
- Study start
- 23 Nov 2020 (actual)
- Primary completion
- 1 Sep 2021 (actual)
- Study completion
- 6 Oct 2021 (actual)
- First posted
- 5 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The research team is investigating administering exogenous surfactant in COVID-19 patients with ARDS. The overall goal is to improve the outcome (mortality) of mechanically ventilated COVID-19 patients. Although the investigators anticipate that clinical outcomes may improve in the small group of patients receiving exogenous surfactant therapy in this small, single center study, the primary goal is to first determine feasibility and safety.
Detailed description
The most severe patients infected by the virus that causes COVID-19 develop severe respiratory failure (called ARDS) and require mechanical ventilation in the intensive care unit to help maintain oxygen delivery to the blood. Often these patients further deteriorate while on mechanical ventilation. This trial will determine the feasibility and safety of a therapy that can potentially improve lung function, reduce the need for mechanical ventilation and hopefully impact mortality.
Adult patients with COVID-19 induced respiratory failure will be randomly assigned to receive either standard treatment or standard treatment plus exogenous surfactant. If enrolled in the latter, exogenous surfactant will be instilled into the lungs within 48 hours of intubation.
The study is founded on extensive research on ARDS for over 30 years, leading to evidence suggesting that exogenous surfactant administration may be beneficial in this disease. Importantly, exogenous surfactant is already utilized all over the world to reduce mortality in preterm infants. When tested in adults with ARDS, it was shown to be well tolerated and safe. Furthermore, clinical and laboratory evidence suggests that this therapy may be most effective in patients with a direct lung infection, and when administered shortly after the patient is intubated. In this study, twenty patients who are proven COVID-19 positive and require MV due to progressive respiratory failure will be randomized to receive either 1) exogenous surfactant (BLES) as soon as possible and within 48 hours of intubation and stabilization, or 2) treatment as usual (will not be treated with surfactant). The overall goal is to improve the outcome (mortality) of mechanically ventilated COVID-19 patients. Although the investigators anticipate that clinical outcomes may improve in the small group of patients receiving exogenous surfactant therapy in this small, single center study, the primary goal is to first determine feasibility and safety. Should the investigators obtain promising results, the data obtained from this study will be used to develop a large trial to test the impact of this therapy on the clinical outcomes, including mortality, associated with COVID-19.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients will be randomly assigned to either receive exogenous surfactant daily for 3 days, or receive standard treatment.
| Arm | Type | Receives |
|---|---|---|
| BLES treatment | Experimental | Drug: Bovine Lipid Extract SurfactantFor patients randomized to the treatment arm, exogenous BLES will be administered as soon as possible and within 48 hours of intubation. BLES will be administered daily for up to 3 doses, or until the patient is liberated from the ventilator. |
| Control | No intervention | –Patients will receive standard treatment and will not receive surfactant. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- age over 18 years
- definitive proof of COVID-19 infection within 48 hours of intubation
- acute respiratory failure with PaO2/FiO2 < 300 requiring intubation
Key exclusion criteria (5 listed)
- known or high suspicion of pre-existing heart failure, unstable angina
- presence of severe shock with hemodynamic instability despite escalating vasopressors
- severe, underlying lung disease (COPD, pulmonary fibrosis, lung cancer. etc.)
- Concurrent treatments are delivered directly into the lung (ie anesthetics etc)
- Diagnosis of pulmonary hemorrhage
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bovine Lipid Extract SurfactantAlso: BLES, Lung Surfactant, BovineBLES will be administered in doses of 50mg/kg ideal bodyweight, at a concentration of 27mg/ml so a total volume of approximately 2ml/kg will be administered. The material will be instilled via the suction catheter through the ET tube so that the ventilation circuit is not broken. Half of the material will be instilled with the patient positioned on their left and right sides, with a pause to allow 5 min of MV between. The procedure will be repeated at, 24 and 48 hours while intubated, so the patient will receive up to 3 doses. To minimize aerosol generation, all patients will be paralyzed during surfactant administration and the ventilator will be paused. The proposed administration technique, surfactant concentration, volume and dosing schedule is based on previous studies, and has shown to be safe in patients with ARDS. | Drug | BLES treatment |
Primary outcome
Adverse events (patient) - Decrease in oxygenation
Time frame: 3 days post-randomization
Count of any decreases in oxygenation, expressed as PaO2 (mmHg) / FiO2 (% oxygen as a decimal), of greater than 20% during the BLES treatment and up to 30 minutes post-treatment. Change will be calculated relative to pre-treatment values.
Adverse events (patient) - Decrease in hemodynamics
Time frame: 3 days post-randomization
Count of any decrease in mean arterial blood pressure >10 mmHg or requirement for >20% increase in vasopressor dose during the BLES procedure and up to 30 minutes post-treatment. Change will be calculated relative to the pre-treatment values.
Adverse event (healthcare worker) - Circuit breach
Time frame: 3 days post-randomization
Number of circuit breaches. Count of any circuit breach immediately prior to and during each BLES treatment procedure will be recorded.
Adverse event (healthcare worker) - COVID-19 symptoms
Time frame: 2 weeks post-randomization
Count of healthcare personnel involved in the BLES procedure developing symptoms and testing positive for COVID-19.
16 secondary outcomes
Change in oxygenation
Time frame: Every 12 hours post-randomization until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days.
Change in Lung compliance
Time frame: Every 12 hours post-randomization until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days.
Ventilated days
Time frame: From ICU admission until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days
Length of ICU stay
Time frame: From ICU admission until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days
Length of hospital stay
Time frame: From hospital admission until hospital discharge or death, whichever comes first, assessed up to 60 days
Mortality
Time frame: 30 days
G-CSF levels (serum inflammatory biomarker)
Time frame: ICU day 0, 1, 3 and 7 (7 days)
GM-CSF levels (serum inflammatory biomarker)
Time frame: ICU day 0, 1, 3 and 7 (7 days)
IFN gamma levels (serum inflammatory biomarker)
Time frame: ICU day 0, 1, 3 and 7 (7 days)
IL-1 beta levels (serum inflammatory biomarker)
Time frame: ICU day 0, 1, 3 and 7 (7 days)
IL-4 levels (serum inflammatory biomarker)
Time frame: ICU day 0, 1, 3 and 7 (7 days)
IL-6 levels (serum inflammatory biomarker)
Time frame: ICU day 0, 1, 3 and 7 (7 days)
IL-10 levels (serum inflammatory biomarker)
Time frame: ICU day 0, 1, 3 and 7 (7 days)
I levels (serum inflammatory biomarker)
Time frame: ICU day 0, 1, 3 and 7 (7 days)
MCP-1 levels (serum inflammatory biomarker)
Time frame: ICU day 0, 1, 3 and 7 (7 days)
TNF alpha levels (serum inflammatory biomarker)
Time frame: ICU day 0, 1, 3 and 7 (7 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jim Lewis, MD principal investigator
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bovine Lipid Extract Surfactant in people with ARDS, Human and COVID-19, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (patient) - Decrease in oxygenation (time frame: 3 days post-randomization). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2021.