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

September 30, 2021 updated by: Augusto Mota, ETICA

A Randomized, Double-blind, Placebo-controlled Safety and Clinical Outcomes Study of Disulfiram in Subjects With Moderate COVID-19

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
140

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • Bahia
      • Salvador, Bahia, Brazil, CEP 41830-492
        • ETICA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

35 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to clinical improvement
Time Frame: 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.
From enrollment to clinical improvement (1 point or more in the WHO score), up to 28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Mean number of days of supplemental oxygen (WHO score ≥4)
Time Frame: Baseline to Day 28
Baseline to Day 28
Time to discharge from the hospital
Time Frame: From baseline to discharge, up to 28 days.
From baseline to discharge, up to 28 days.
Percentage of subjects that are discharged by Day 8
Time Frame: At 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.
Time Frame: Baseline to Day 28
Baseline to 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.
Time Frame: Baseline to Day 28
Baseline to Day 28
Mean number of days subjects were in the Intensive Care Unit (ICU)
Time Frame: Baseline to Day 28
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.
Time Frame: Baseline to Day 28
Baseline to Day 28
28-day mortality
Time Frame: At Day 28
At Day 28

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from baseline to Day 8 and Day 15 for cytokine IL-18
Time Frame: Baseline, Day 8 and Day 15
Mean change and percent change
Baseline, Day 8 and Day 15
Percentage of subjects requiring supplemental oxygen (WHO Score ≥4) by Day 8, 15, and 28.
Time Frame: Baseline, Day 8, Day 15 and Day 28
Baseline, Day 8, Day 15 and Day 28
Percentage of subjects that are discharged by Day 15 and Day 28.
Time Frame: 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.
Time Frame: Baseline to Day 8, 15
Baseline to Day 8, 15
Percentage of subjects admitted to the Intensive Care Unit.
Time Frame: Baseline to Day 28
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.
Time Frame: 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.
Time Frame: Baseline, Day 8 and Day 15
Mean change and percent change
Baseline, Day 8 and Day 15
Percent change in total lymphocyte count from baseline to Day 8 and Day 15
Time Frame: Baseline, 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)
Time Frame: Baseline, Day 8 and Day 15
Mean change and percent change
Baseline, Day 8 and Day 15
Change from baseline to Day 8 and Day 15 for Cytokine TNF-α
Time Frame: Baseline, Day 8 and Day 15
Mean change and percent change
Baseline, Day 8 and Day 15
Change from baseline to Day 8 and Day 15 for cytokine IL-1β
Time Frame: Baseline, Day 8 and Day 15
Mean change and percent change
Baseline, Day 8 and Day 15
Change from baseline to Day 8 and Day 15 for cytokine IL-1RA
Time Frame: Baseline, Day 8 and Day 15
Mean change and percent change
Baseline, Day 8 and Day 15
Change from baseline to Day 8 and Day 15 for cytokine IL-6
Time Frame: Baseline, Day 8 and Day 15
Mean change and percent change
Baseline, Day 8 and Day 15
Change from baseline to Day 8 and Day 15 for cytokine IL-8
Time Frame: Baseline, Day 8 and Day 15
Mean change and percent change
Baseline, Day 8 and Day 15
Change from baseline to Day 8 and Day 15 for cytokine IL-10
Time Frame: Baseline, Day 8 and Day 15
Mean change and percent change
Baseline, Day 8 and Day 15
Change from baseline to Day 8 and Day 15 for Lactate Dehydrogenase (LDH)
Time Frame: Baseline, Day 8 and Day 15
Mean change and percent change
Baseline, Day 8 and Day 15
Change from baseline to Day 8 and Day 15 for D-dimer
Time Frame: Baseline, Day 8 and Day 15
Mean change and percent change
Baseline, Day 8 and Day 15
Association between baseline and worst post-baseline WHO score
Time Frame: Baseline to Day 28
Baseline to Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ETICA

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Spring Research Foundation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Augusto Mota, MD/PhD, ETICA
  • Study Director: Wendy Cousin, PhD, Spring Research Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 20, 2020

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 10, 2021

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 25, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 18, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 19, 2020

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 20, 2020

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 8, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 30, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SPR-001-201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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