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

NCT04594343 | Completed Phase 2 DMC

• 1 other identifier: SPR-001-201
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

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.

Conditions

Covid19

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  Baseline to Day 28

• 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 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 Outcomes (18)

• Change from baseline to Day 8 and Day 15 for cytokine IL-18

  Baseline, Day 8 and Day 15

• 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

Study Arms (2)

Disulfiram

EXPERIMENTAL

Drug: Disulfiram

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Disulfiram DRUG

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

Also known as: Antabuse

Disulfiram

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• ETICA: lead
• Spring Research Foundation: collaborator

Study Sites (1)

ETICA

Salvador, Estado de Bahia, CEP 41830-492, Brazil

Location

Related Publications (1)

• 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.

  PMID: 35285015 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Disulfiram

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds

Study Officials

• Augusto Mota, MD/PhD

  ETICA

  PRINCIPAL INVESTIGATOR

• Wendy Cousin, PhD

  Spring Research Foundation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: October 18, 2020
• First Posted: October 20, 2020
• Study Start: November 20, 2020
• Primary Completion: September 10, 2021
• Study Completion: September 25, 2021
• Last Updated: October 8, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share

Locations

BR (1)