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London's Exogenous Surfactant Study for COVID19 (LESSCOVID)

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ClinicalTrials.gov Identifier: NCT04375735
Recruitment Status : Not yet recruiting
First Posted : May 5, 2020
Last Update Posted : June 11, 2020
Sponsor:
Collaborator:
London Health Sciences Centre
Information provided by (Responsible Party):
Lawson Health Research Institute

Tracking Information
First Submitted Date  ICMJE April 22, 2020
First Posted Date  ICMJE May 5, 2020
Last Update Posted Date June 11, 2020
Estimated Study Start Date  ICMJE July 1, 2020
Estimated Primary Completion Date January 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 4, 2020)
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 4, 2020)
  • 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. ]
    PaO2 (in mmHg) / FiO2 (percentage oxygen expressed as a decimal) ratios captured from clinical chart
  • 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. ]
    Lung compliance captured from the ventilators, expressed in mL/cm H2O.
  • 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 ]
    The number of days the patient is receiving mechanical ventilation.
  • 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 ]
    The number of days the patient is admitted to the ICU
  • Length of hospital stay [ Time Frame: From hospital admission until hospital discharge or death, whichever comes first, assessed up to 60 days ]
    The number of days the patient is admitted to the hospital
  • Mortality [ Time Frame: 30 days ]
    Number of patients who die within 30 days of ICU admission
  • G-CSF levels (serum inflammatory biomarker) [ Time Frame: ICU day 0, 1, 3 and 7 (7 days) ]
    G-CSF, in pg/mL, from multiplex cytokine arrays
  • GM-CSF levels (serum inflammatory biomarker) [ Time Frame: ICU day 0, 1, 3 and 7 (7 days) ]
    GM-CSF, in pg/mL, from multiplex cytokine arrays
  • IFN gamma levels (serum inflammatory biomarker) [ Time Frame: ICU day 0, 1, 3 and 7 (7 days) ]
    IFN gamma, in pg/mL, from multiplex cytokine arrays
  • IL-1 beta levels (serum inflammatory biomarker) [ Time Frame: ICU day 0, 1, 3 and 7 (7 days) ]
    IL-1 beta, in pg/mL, from multiplex cytokine arrays
  • IL-4 levels (serum inflammatory biomarker) [ Time Frame: ICU day 0, 1, 3 and 7 (7 days) ]
    IL-4, in pg/mL, from multiplex cytokine arrays
  • IL-6 levels (serum inflammatory biomarker) [ Time Frame: ICU day 0, 1, 3 and 7 (7 days) ]
    IL-6, in pg/mL, from multiplex cytokine arrays
  • IL-10 levels (serum inflammatory biomarker) [ Time Frame: ICU day 0, 1, 3 and 7 (7 days) ]
    IL-10, in pg/mL, from multiplex cytokine arrays
  • I levels (serum inflammatory biomarker) [ Time Frame: ICU day 0, 1, 3 and 7 (7 days) ]
    I, in pg/mL, from multiplex cytokine arrays
  • MCP-1 levels (serum inflammatory biomarker) [ Time Frame: ICU day 0, 1, 3 and 7 (7 days) ]
    MCP-1, in pg/mL, from multiplex cytokine arrays
  • TNF alpha levels (serum inflammatory biomarker) [ Time Frame: ICU day 0, 1, 3 and 7 (7 days) ]
    TNF alpha, in pg/mL, from multiplex cytokine arrays
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE London's Exogenous Surfactant Study for COVID19
Official Title  ICMJE Phase I/II Trial: Exogenous Surfactant Administration for Patients With COVID-19
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Patients will be randomly assigned to either receive exogenous surfactant daily for 3 days, or receive standard treatment.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • ARDS, Human
  • COVID-19
Intervention  ICMJE Drug: Bovine Lipid Extract Surfactant
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.
Other Names:
  • BLES
  • Lung Surfactant
  • Bovine
Study Arms  ICMJE
  • Experimental: BLES treatment
    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.
    Intervention: Drug: Bovine Lipid Extract Surfactant
  • No Intervention: Control
    Patients will receive standard treatment and will not receive surfactant.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 4, 2020)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2021
Estimated Primary Completion Date January 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. age over 18 years
  2. definitive proof of COVID-19 infection within 48 hours of intubation
  3. acute respiratory failure with PaO2/FiO2 < 300 requiring intubation

Exclusion Criteria:

  1. known or high suspicion of pre-existing heart failure, unstable angina
  2. presence of severe shock with hemodynamic instability despite escalating vasopressors
  3. severe, underlying lung disease (COPD, pulmonary fibrosis, lung cancer. etc.)
  4. Concurrent treatments are delivered directly into the lung (ie anesthetics etc)
  5. Diagnosis of pulmonary hemorrhage
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gordon Barkwell, MSc 519-685-8500 ext 55665 gordon.barkwell@lhsc.on.ca
Contact: Tracey Bentall 519-663-3150 ext 32546 traceyc.bentall@lhsc.on.ca
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04375735
Other Study ID Numbers  ICMJE 9890
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Lawson Health Research Institute
Study Sponsor  ICMJE Lawson Health Research Institute
Collaborators  ICMJE London Health Sciences Centre
Investigators  ICMJE
Principal Investigator: Jim Lewis, MD Lawson Health Research Institute
PRS Account Lawson Health Research Institute
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP