Covid19Phase 2NCT04594343
Clinical Study to Evaluate the Effects of Disulfiram in Patients With Moderate COVID-19
A Phase 2 study testing Disulfiram in people with Covid19, run by ETICA at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Disulfiram
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 1 siteBrazil
- Study dates
- 20 Nov 2020to 25 Sep 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects may be enrolled in the study only if all the inclusion criteria are met.
- Male and female subjects, age 35 or older.
- Female subjects of childbearing potential must have a negative hCG (in urine or blood) pregnancy test.
- An International Ethics Committee (IEC) approved informed consent is signed and dated prior to any study-related activities.
- 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.
- Have the ability to understand the requirements of the study and is willing to comply with all study procedures and visits.
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- Respiratory rate: ≤ 30 per minute.
- Use supplemental O2 via nasal cannula or equivalent.
- Currently hospitalized ≤ 5 days.
- PCR test or rapid antigen test confirming SARS-CoV-2.
- In the opinion of the investigator, able to participate in the study.
Who cannot join
- Subjects may not be enrolled in the study if any of the exclusion criteria apply.
- Admission into the Intensive Care Unit (ICU) at screening and baseline.
- Clinically active Hepatitis.
- ALT or AST > 3 times the upper limit of normal.
- Need for invasive or non-invasive ventilation at screening and baseline.
- Stage 4 severe chronic kidney disease or requiring dialysis or estimated GFR < 30.
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- Known allergy to disulfiram.
- 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.
- Participation in any other interventional trial within 30 days prior to enrollment.
- 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).
- 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.
- Fully vaccinated for COVID-19 (number of doses as per manufacturer recommendation.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Covid19
- Being tested
- Disulfiram, Placebo
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DisulfiramDrug
Also called Antabuse
The subject will receive 500 mg of disulfiram orally or enterally through NG tube if in mechanical ventilation once daily for 14 days
PlaceboDrug
The subject will receive a matching placebo orally or enterally through NG tube if in mechanical ventilation once daily for 14 days
| Study group | Role | What they receive |
|---|---|---|
| Disulfiram | Experimental | Not described Receives: Drug: Disulfiram |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to clinical improvement
Defined as the time from baseline to the first post-baseline assessment with an improvement in WHO score of ≥1 point.
Measured: From enrollment to clinical improvement (1 point or more in the WHO score), up to 28 days
Secondary outcomes (8)
Mean number of days of supplemental oxygen (WHO score ≥4)
Measured: Baseline to Day 28
Time to discharge from the hospital
Measured: From baseline to discharge, up to 28 days.
Percentage of subjects that are discharged by Day 8
Measured: 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.
Measured: 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.
Measured: Baseline to Day 28
Mean number of days subjects were in the Intensive Care Unit (ICU)
Measured: 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.
Measured: Baseline to Day 28
28-day mortality
Measured: At Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2020
- Study start20 Nov 2020
- Primary completion10 Sep 2021
- Study completion25 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- ETICA
- Sponsor type
- University, hospital or other
- Collaborators
- Spring Research Foundation
- Responsible party
- Principal investigator, Augusto Mota, ETICA
- Investigators
- Augusto Mota, MD/PhD, Principal investigator, ETICAWendy Cousin, PhD, Study director, Spring Research Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04594343
- Sponsor's protocol ID
- SPR-001-201
- Status last verified
- Sep 2021
- First submitted
- 18 Oct 2020
- Last updated
- 8 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Saifi MA, Shaikh AS, Kaki VR, Godugu C. Disulfiram prevents collagen crosslinking and inhibits renal fibrosis by inhibiting lysyl oxidase enzymes. J Cell Physiol. 2022 May;237(5):2516-2527. doi: 10.1002/jcp.30717. Epub 2022 Mar 13.
PubMed 35285015
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Safety and Clinical Outcomes Study of Disulfiram in Subjects With Moderate COVID-19
- ClinicalTrials.gov ID
- NCT04594343
- Acronym / sponsor ID
- SPR-001-201
- Conditions
- Covid19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- ETICAUniversity, hospital or other
- Collaborators
- Spring Research Foundation
- Study start
- 20 Nov 2020 (actual)
- Primary completion
- 10 Sep 2021 (actual)
- Study completion
- 25 Sep 2021 (actual)
- First posted
- 20 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Disulfiram | Experimental | Drug: Disulfiram |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Subjects may be enrolled in the study only if all the inclusion criteria are met.
- Male and female subjects, age 35 or older.
- Female subjects of childbearing potential must have a negative hCG (in urine or blood) pregnancy test.
- An International Ethics Committee (IEC) approved informed consent is signed and dated prior to any study-related activities.
- 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.
Key exclusion criteria (12 listed)
- Subjects may not be enrolled in the study if any of the exclusion criteria apply.
- Admission into the Intensive Care Unit (ICU) at screening and baseline.
- Clinically active Hepatitis.
- ALT or AST > 3 times the upper limit of normal.
- Need for invasive or non-invasive ventilation at screening and baseline.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DisulfiramAlso: AntabuseThe subject will receive 500 mg of disulfiram orally or enterally through NG tube if in mechanical ventilation once daily for 14 days | Drug | Disulfiram |
| PlaceboThe subject will receive a matching placebo orally or enterally through NG tube if in mechanical ventilation once daily for 14 days | Drug | Placebo |
Primary outcome
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.
8 secondary outcomes
Mean number of days of supplemental oxygen (WHO score ≥4)
Time frame: Baseline to Day 28
Time to discharge from the hospital
Time frame: From baseline to discharge, up to 28 days.
Percentage of subjects that are discharged by Day 8
Time frame: 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
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
Mean number of days subjects were in the Intensive Care Unit (ICU)
Time frame: 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
28-day mortality
Time frame: At Day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2021.
- Derived from this study: PubMed 35285015Saifi MA, Shaikh AS, Kaki VR, Godugu C. Disulfiram prevents collagen crosslinking and inhibits renal fibrosis by inhibiting lysyl oxidase enzymes. J Cell Physiol. 2022 May;237(5):2516-2527. doi: 10.1002/jcp.30717. Epub 2022 Mar 13.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Augusto Mota, MD/PhD principal investigator
ETICA
Wendy Cousin, PhD study director
Spring Research Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Disulfiram in people with Covid19, run by ETICA at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to clinical improvement (time frame: From enrollment to clinical improvement (1 point or more in the WHO score), up to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04594343, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2021.