Corona Virus Infection, COVID, COVID-19
Conditions
Brief summary
Studying the efficacy of IL-6 inhibition utilizing single or double dose subcutaneous administration of Sarilumab in patients with severe respiratory distress caused by COVID19 regarding improvement in oxygen demands and other clinical outcomes.
Detailed description
At the time of writing this protocol, there does not exist any strategy to treat acute respiratory distress syndrome associated with COVID-19. Due to the overwhelming health crisis facing a large portion of the population, and due to lack of standardization or clinical approach to management of severe respiratory failure short of standard of care with oxygenation and supportive measures, we elected to embark on this study to evaluate the role of IL-6 stimulating the immune system and the effect of inhibiting signal propagation on clinical outcome. For this study, Sarilumab, an FDA approved IL-6 receptor antagonist, currently used for severe rheumatoid arthritis, has been selected. The dose and administration of therapy used for the study conforms to the current FDA recommendation for the primary use of Sarilumab.
Interventions
DRUGSarilumab 200 MG/1.14 ML Subcutaneous Solution
At the time of enrollment, the intervention arm subjects are administered single or double dose of study drug while the placebo arm subjects are administered the placebo drug (normal saline). Subjects will be assigned to the intervention or placebo arm in random order.
DRUGPlacebo
Normal saline 0.9% 1.14 mL Subcutaneous x 1 or 2 dose(s)
Sponsors
BayCare Health System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Confirmed COVID-19 via centralized RT-PCR testing for SARS-CoV2 infection performed at BayCare Health System Laboratory or associated and accredited laboratory. 2. Subjects must be hospitalized. 3. Document fever of 100.4 F or more during hospitalization and prior to enrollment. 4. Evidence of abnormal chest imaging chest x-ray or CT. 5. Moderate to severe respiratory distress requiring oxygen supplementation as defined by criteria listed below. Oxygen saturation (Sao2) of 92% or less on room air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 200 mm Hg, on ventilator settings that include PEEP ≥5 cm H2O. 6. Subjects may have active co-infection with other respiratory pathogens. 7. Males and non-pregnant females at least 18 years of age.
Exclusion criteria
1. The subject or Legally Authorized Representative is unable to provide consent in person or by phone. 2. The subject is participating in any other clinical trial for treatment of COVID 19 or any other treatment related clinical trial for a concurrent disease. No plans for additional COVID trials. 3. The subject does not meet criteria for moderate to severe respiratory distress. 4. The presence of any of the following lab abnormalities. ANC \<2000/mm3, Platelet count \<50,000/mm3, ALT/AST \>6x ULN 5. Prior utilization of any IL-6 inhibitors or receptor antagonists at any time in patient's life, JAK inhibitors, DMARDS(Except Hydroxychloroquine), long term, chronic steroid use (more than 6 months) or mTOR inhibitors. 6. The subject has history of organ or bone marrow transplant. 7. History of active or incompletely treated Tuberculosis (TB).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to clinical outcome improvement | Time to improvement up to 28 days | Time from randomization to improvement in oxygenation. Improvement in oxygenation is defined as SpO2/FiO2 improvement by 100 or greater. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The number of patients with a need for intubation | Up to 28 days | — |
| Time on ventilator | Up to 28 days | — |
| Fever resolution | Up to 28 days | A continuous period at least 48 hours without a recorded temperature equal or more than 100.4 F. |
| Hemodynamic improvement to normal range | Up to 28 days | Heart rate |
| Improvement or normalization in CBC | At 48 hours post intervention up to 28 days | CBC with differential |
| Time to objective improvement noted on chest imaging | Up to 28 days | — |
| Time from randomization to hospital discharge | Up to 28 days | — |
| Death | Up to 28 days | — |
| Time to improvement in oxygenation | Time to improvement up to 28 days | Time from randomization to no requirement of any oxygen supplementation with Oxygen saturation of \> =92% at rest. |
| Improvement or normalization in LDH | At 48 hours post intervention up to 28 days | LDH |
| Improvement or normalization in Lactic Acid | At 48 hours post intervention up to 28 days | Lactic Acid |
| Improvement or normalization in Procalcitonin | At 48 hours post intervention up to 28 days | Procalcitonin |
| Improvement or normalization in Ferritin | At 48 hours post intervention up to 28 days | Ferritin |
| Improvement or normalization in CRP | At 48 hours post intervention up to 28 days | CRP |
| Improvement or normalization in D-Dimer | At 48 hours post intervention up to 28 days | D-Dimer |
| Improvement or normalization in IL-6 | At 48 hours post intervention up to 28 days | IL-6 |
| Improvement or normalization in CMP | At 48 hours post intervention up to 28 days | Comprehensive Metabolic Panel |
Countries
United States
Outcome results
None listed