Coronavirus Infection, Sepsis
Conditions
Brief summary
Randomized, double-blind, placebo-controlled trial comparing 2 doses of SY-005 (recombinant human Annexin A5) to placebo in patients with severe coronavirus 2019 disease in a single hospital centre with 2 intensive care units
Interventions
DRUGrecombinant human annexin A5
recombinant human annexin A5, manufactured as SY-005
DRUGPlacebo
Normal saline 50 ml
Sponsors
Ontario Ministry of Colleges and Universities
London Health Sciences Foundation
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 19 years 2. Positive test for SARS-CoV-2 virus (anytime during current illness episode) 3. Admitted to intensive care for organ failure support (at least one of vasopressor, non-invasive or invasive ventilation)
Exclusion criteria
1. Known allergy to any of the ingredients or components of the investigational product 2. Known pregnancy 3. Moribund and not expected to survive beyond 24 hours 4. Known or suspected risk for serious bleeding complications (note that Disseminated Intravascular Coagulopathy (DIC) is an expected finding in patient with sepsis and COVID-19 disease and is not an exclusion criterion on its own) 5. Acute or chronic renal failure (dialysis dependent)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Enrollment | 12 months | Participants enrolled per site per month with success defined as enrollment \>= 50% of screened eligible patients |
| Protocol adherence | 7 days | Delivery of investigational product within 1 hour of scheduled dose; success defined as \>= 90% |
| Data completeness | 12 months | Case Report Forms completed with \<10% missing data after verification and monitoring |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with anti-annexin A5 antibodies | 21 days | Anti-annexin A5 antibodies |
| Organ failure | 30 days | Sequential Organ Failure Assessment (SOFA) at 30 days; range 0 (normal) to 24 |
| Organ function at end of treatment measured with SOFA | 7 days | SOFA at end of treatment (EOT) |
| Organ function at end of treatment measured with Multiple Organ Dysfunction Score (MODS) | 7 days | MODS at end of treatment (EOT); range 0 (normal) to 24 |
| Individual organ function scores at EOT measured with SOFA | 30 days | SOFA for individual organ systems |
| Individual organ function scores at 30 days measured with SOFA | 30 days | SOFA for individual organ systems |
| Individual organ function scores at EOT measured with MODS | 30 days | MODS for individual organ systems |
| Number of serious adverse events (SAE) | 60 days | SAE |
| Plasma annexin A5 levels daily days 1-8 (treatment period) and on day 14 | 14 days | Annexin A5 will be measured daily during treatment and on day 14 |
| Mortality at 60 days | 60 days | All cause mortality |
| Hospital mortality | 60 days | Hospital mortality censored at 60 days |
| Ventilator-free days | 30 days | Days alive and off ventilator at 30 days |
| ICU-free days | 30 days | Days alive and not in ICU at 30 days |
| Number of participants with persistent organ dysfunction | 30 days | MODS score greater or equal to 2 in any organ system at day 30 |
| Individual organ function scores at 30 days measured with MODS | 30 days | MODS for individual organ systems |
| Maximum plasma concentration (Cmax) of annexin A5 (SY-005) | 1 day | Pharmacokinetic profile on day 1 |
| Elimination half-life of annexin A5 (SY-005) | 1 day | Pharmacokinetic profile on day 1 |
Countries
Canada
Outcome results
None listed