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

NCT ID: NCT04594343

Last Updated: 2021-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-20
• Study Completion Date: 2021-09-25

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.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Disulfiram

Group Type: EXPERIMENTAL

Disulfiram

Intervention Type: DRUG

The subject will receive 500 mg of disulfiram orally or enterally through NG tube if in mechanical ventilation once daily for 14 days

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Disulfiram

The subject will receive 500 mg of disulfiram orally or enterally through NG tube if in mechanical ventilation once daily for 14 days

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Antabuse

Eligibility Criteria

Inclusion Criteria

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

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.

• Minimum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spring Research Foundation

NETWORK

Sponsor Role: collaborator

ETICA

OTHER

Sponsor Role: lead

Responsible Party

Augusto Mota

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Augusto Mota, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

ETICA

Wendy Cousin, PhD

Role: STUDY_DIRECTOR

Spring Research Foundation

Locations

ETICA

Salvador, Estado de Bahia, Brazil

Countries

Brazil

References

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.

Reference Type: DERIVED

PMID: 35285015 (View on PubMed)

Other Identifiers

SPR-001-201

Identifier Type: -

Identifier Source: org_study_id