Clinical Study to Evaluate the Effects of Disulfiram in Patients With Moderate COVID-19

Sponsor
ETICA (Other)
Overall Status
Completed
CT.gov ID
NCT04594343
Collaborator
Spring Research Foundation (Other)
140
Enrollment
1
Location
2
Arms
10.2
Actual Duration (Months)
13.8
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
140 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
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.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.
Masking:
Quadruple (Participant, Care Provider, 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.
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-controlled Safety and Clinical Outcomes Study of Disulfiram in Subjects With Moderate COVID-19
Actual Study Start Date :
Nov 20, 2020
Actual Primary Completion Date :
Sep 10, 2021
Actual Study Completion Date :
Sep 25, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: Disulfiram

Drug: Disulfiram
The subject will receive 500 mg of disulfiram orally or enterally through NG tube if in mechanical ventilation once daily for 14 days
Other Names:
  • Antabuse
  • Placebo Comparator: Placebo

    Drug: Placebo
    The subject will receive a matching placebo orally or enterally through NG tube if in mechanical ventilation once daily for 14 days

    Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. Mean number of days of supplemental oxygen (WHO score ≥4) [Baseline to Day 28]

    2. Time to discharge from the hospital [From baseline to discharge, up to 28 days.]

    3. Percentage of subjects that are discharged by Day 8 [At Day 8]

    4. 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]

    5. 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]

    6. Mean number of days subjects were in the Intensive Care Unit (ICU) [Baseline to Day 28]

    7. 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]

    8. 28-day mortality [At Day 28]

    Other Outcome Measures

    1. Change from baseline to Day 8 and Day 15 for cytokine IL-18 [Baseline, Day 8 and Day 15]

      Mean change and percent change

    2. Percentage of subjects requiring supplemental oxygen (WHO Score ≥4) by Day 8, 15, and 28. [Baseline, Day 8, Day 15 and Day 28]

    3. Percentage of subjects that are discharged by Day 15 and Day 28. [Day 15 and Day 28]

    4. 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]

    5. Percentage of subjects admitted to the Intensive Care Unit. [Baseline to Day 28]

    6. 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]

    7. Change in total neutrophil count from baseline to Day 8 and 15. [Baseline, Day 8 and Day 15]

      Mean change and percent change

    8. Percent change in total lymphocyte count from baseline to Day 8 and Day 15 [Baseline, Day 8 and Day 15]

    9. 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

    10. Change from baseline to Day 8 and Day 15 for Cytokine TNF-α [Baseline, Day 8 and Day 15]

      Mean change and percent change

    11. Change from baseline to Day 8 and Day 15 for cytokine IL-1β [Baseline, Day 8 and Day 15]

      Mean change and percent change

    12. Change from baseline to Day 8 and Day 15 for cytokine IL-1RA [Baseline, Day 8 and Day 15]

      Mean change and percent change

    13. Change from baseline to Day 8 and Day 15 for cytokine IL-6 [Baseline, Day 8 and Day 15]

      Mean change and percent change

    14. Change from baseline to Day 8 and Day 15 for cytokine IL-8 [Baseline, Day 8 and Day 15]

      Mean change and percent change

    15. Change from baseline to Day 8 and Day 15 for cytokine IL-10 [Baseline, Day 8 and Day 15]

      Mean change and percent change

    16. Change from baseline to Day 8 and Day 15 for Lactate Dehydrogenase (LDH) [Baseline, Day 8 and Day 15]

      Mean change and percent change

    17. Change from baseline to Day 8 and Day 15 for D-dimer [Baseline, Day 8 and Day 15]

      Mean change and percent change

    18. Association between baseline and worst post-baseline WHO score [Baseline to Day 28]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    35 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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 exclusion criteria apply.

    1. Admission into the Intensive Care Unit (ICU) at screening and baseline.

    2. Clinically active Hepatitis.

    3. ALT or AST > 3 times the upper limit of normal.

    4. Need for invasive or non-invasive ventilation at screening and baseline.

    5. Stage 4 severe chronic kidney disease or requiring dialysis or estimated GFR < 30.

    6. Known allergy to disulfiram.

    7. Treatment with any of the medications listed below within 7 days prior to the baseline visit 1: Amprenavir, Dronabinol, Hydantoins, Metronidazole, Ritonavir, Benznidazole, Dyphylline, Idelalisib, Naltrexone, Sertraline, Chloral Hydrate, Ethanol, Immuno-modulatory drugs, Paclitaxel, Tinidazole, Cocaine, Ethotoin, Ixabepilone, Phenytoin, Tipranavir, Cyclosporine, Fosphenytoin, Lithium, Pimozide, Tranylcypromine, Dasabuvir, Guaifenesin, Mesoridazine, Pirfenidone.

    8. Participation in any other interventional trial within 30 days prior to enrollment.

    9. Active malignancy (excluding basal cell carcinoma, squamous cell carcinoma, in situ cervical cancer, or adenocarcinoma of the prostate with low or very low-risk categories by NCCN criteria).

    10. Any surgical or medical condition which in the opinion of the investigator may interfere with participation in the study or which may affect the outcome of the study.

    11. Fully vaccinated for COVID-19 (number of doses as per manufacturer recommendation.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1ETICASalvadorBahiaBrazilCEP 41830-492

    Sponsors and Collaborators

    • ETICA
    • Spring Research Foundation

    Investigators

    • Principal Investigator: Augusto Mota, MD/PhD, ETICA
    • Study Director: Wendy Cousin, PhD, Spring Research Foundation

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Augusto Mota, Principal Investigator, ETICA
    ClinicalTrials.gov Identifier:
    NCT04594343
    Other Study ID Numbers:
    • SPR-001-201
    First Posted:
    Oct 20, 2020
    Last Update Posted:
    Oct 8, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 8, 2021