Covid19
Conditions
Brief summary
This clinical trial evaluates the safety, efficacy, and biomarker levels of FDA-approved drug disulfiram in the treatment of adult subjects hospitalized with moderate COVID-19. Disulfiram may limit the hyperinflammatory response associated with COVID-19 and reduce the risk of progression to severe illness. Subjects will be screened and randomized to receive either daily administration of oral disulfiram or placebo for 14 days. Subjects will be followed up on Day 28.
Detailed description
COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent COVID-19 or infection with SARS-CoV-2 or therapeutic agent to treat COVID-19. The ongoing COVID-19 pandemic has demonstrated increased risk to those with an aging immune system. The elderly and those with comorbidities are reported as being the most susceptible to COVID-19, which may be due to a higher basal state of inflammation (inflammaging) and a primed inflammasome pathway. Disulfiram, an FDA-approved drug for the treatment of alcohol dependence, has a potential for limiting the hyperinflammatory response associated with COVID-19. Specifically, the drug inhibits gasdermin D pore formation, reducing pyroptosis and netosis and could target the root cause of hyperinflammation, weakening the cytokine storm and therefore reducing the risk of progression to severe illness. This is a stratified, randomized, double-blind, placebo-controlled study of disulfiram in hospitalized subjects over the age of 50 diagnosed with moderate COVID-19. Up to 200 subjects are planned to be enrolled and randomized (1:1) to either receive 500 mg of disulfiram (active product) or placebo, orally (po) or enterally (only in patients that require mechanical ventilation) once daily for fourteen (14) days in addition to standard of care. Stratification will be done at randomization based on age and comorbidities.
Interventions
DRUGDisulfiram
The subject will receive 500 mg of disulfiram orally or enterally through NG tube if in mechanical ventilation once daily for 14 days
DRUGPlacebo
The subject will receive a matching placebo orally or enterally through NG tube if in mechanical ventilation once daily for 14 days
Sponsors
Spring Research Foundation
ETICA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
In order to minimize bias due to key baseline characteristics that can impact clinical outcomes, the randomization will be stratified 1:1 to placebo or active product based on age and comorbidities.
Intervention model description
Subjects will be randomized to receive either the active product (disulfiram) or placebo. Disulfiram will be dosed 500 mg daily for a total of 14 days of treatment. A matching placebo will be given using the same dosing schedule.
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects may be enrolled in the study only if all the inclusion criteria are met. 1. Male and female subjects, age 35 or older. 2. Female subjects of childbearing potential must have a negative hCG (in urine or blood) pregnancy test. 3. An International Ethics Committee (IEC) approved informed consent is signed and dated prior to any study-related activities. 4. Willing to abstain from any alcohol or substances containing alcohol (including medications, personal hygiene products, salad dressing) within 24 hours prior to treatment and for 14 days after treatment concludes. 5. Have the ability to understand the requirements of the study and is willing to comply with all study procedures and visits. 6. Respiratory rate: ≤ 30 per minute. 7. Use supplemental O2 via nasal cannula or equivalent. 8. Currently hospitalized ≤ 5 days. 9. PCR test or rapid antigen test confirming SARS-CoV-2. 10. In the opinion of the investigator, able to participate in the study.
Exclusion criteria
Subjects may not be enrolled in the study if any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to clinical improvement | From enrollment to clinical improvement (1 point or more in the WHO score), up to 28 days | Defined as the time from baseline to the first post-baseline assessment with an improvement in WHO score of ≥1 point. |
Secondary
| Measure | Time frame |
|---|---|
| Time to discharge from the hospital | From baseline to discharge, up to 28 days. |
| Percentage of subjects that are discharged by Day 8 | At Day 8 |
| Percentage of subjects that worsened 1 or more points on the WHO Ordinal Scale, from baseline to any post baseline assessment through Day 28. | Baseline to Day 28 |
| Mean number of days of supplemental oxygen (WHO score ≥4) | Baseline to Day 28 |
| Mean number of days subjects were in the Intensive Care Unit (ICU) | Baseline to Day 28 |
| Percentage of subjects that were on non-invasive ventilation or high flow oxygen devices or invasive mechanical ventilation (WHO Score 5 or 6) over the 28-day period. | Baseline to Day 28 |
| 28-day mortality | At Day 28 |
| Mean number of days of non-invasive ventilation or high flow oxygen devices or invasive mechanical ventilation (WHO Score 5 or 6) over the 28-day period. | Baseline to Day 28 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to Day 8 and Day 15 for Cytokine TNF-α | Baseline, Day 8 and Day 15 | Mean change and percent change |
| Change from baseline to Day 8 and Day 15 for cytokine IL-1β | Baseline, Day 8 and Day 15 | Mean change and percent change |
| Change from baseline to Day 8 and Day 15 for cytokine IL-1RA | Baseline, Day 8 and Day 15 | Mean change and percent change |
| Change from baseline to Day 8 and Day 15 for cytokine IL-6 | Baseline, Day 8 and Day 15 | Mean change and percent change |
| Change from baseline to Day 8 and Day 15 for cytokine IL-18 | Baseline, Day 8 and Day 15 | Mean change and percent change |
| Change from baseline to Day 8 and Day 15 for cytokine IL-10 | Baseline, Day 8 and Day 15 | Mean change and percent change |
| Change from baseline to Day 8 and Day 15 for Lactate Dehydrogenase (LDH) | Baseline, Day 8 and Day 15 | Mean change and percent change |
| Change from baseline to Day 8 and Day 15 for D-dimer | Baseline, Day 8 and Day 15 | Mean change and percent change |
| Association between baseline and worst post-baseline WHO score | Baseline to Day 28 | — |
| Change from baseline to Day 8 and Day 15 for cytokine IL-8 | Baseline, Day 8 and Day 15 | Mean change and percent change |
| Percentage of subjects requiring supplemental oxygen (WHO Score ≥4) by Day 8, 15, and 28. | Baseline, Day 8, Day 15 and Day 28 | — |
| Percentage of subjects that are discharged by Day 15 and Day 28. | Day 15 and Day 28 | — |
| Percentage of subjects that worsened 1 or more points on the WHO Ordinal Scale from baseline through Day 8 and Day 15. | Baseline to Day 8, 15 | — |
| Percentage of subjects admitted to the Intensive Care Unit. | Baseline to Day 28 | — |
| Percentage of subjects that improved 1 or more points on the WHO Ordinal Scale from baseline to Day 8, 15, and 28. | Baseline to Day 8, 15, and 28 | — |
| Change in total neutrophil count from baseline to Day 8 and 15. | Baseline, Day 8 and Day 15 | Mean change and percent change |
| Percent change in total lymphocyte count from baseline to Day 8 and Day 15 | Baseline, Day 8 and Day 15 | — |
| Change from baseline to Day 8 and Day 15 for neutrophil-derived circulating free DNA (cf-DNA/NETs) | Baseline, Day 8 and Day 15 | Mean change and percent change |
Countries
Brazil
Outcome results
None listed