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

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ClinicalTrials.gov Identifier: NCT04594343
Recruitment Status : Recruiting
First Posted : October 20, 2020
Last Update Posted : November 30, 2020
Sponsor:
Collaborator:
Spring Research Foundation
Information provided by (Responsible Party):
Augusto Mota, ETICA

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 disease Intervention/treatment Phase
Covid19 Drug: Disulfiram Drug: Placebo 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. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 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.

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 : November 20, 2020
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Disulfiram

Arm Intervention/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 Name: 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




Primary Outcome Measures :
  1. Change from baseline to day 7 for cytokine IL-18 [ Time Frame: Baseline to Day 7 ]

Secondary Outcome Measures :
  1. Percentage of subjects that do not require invasive mechanical ventilation [ Time Frame: 14 Days ]
  2. Mean number of days of invasive mechanical ventilation for those subjects requiring invasive mechanical ventilation [ Time Frame: 14 Days ]
  3. Mean number of days of non-invasive ventilation for those subjects requiring non-invasive ventilation [ Time Frame: 14 Days ]
  4. Mean number of days of supplemental oxygen [ Time Frame: 14 Days ]
  5. Percentage of subjects that deteriorate 1 or more points in the 7-point WHO Ordinal Scale from baseline to Day 14 [ Time Frame: Baseline to Day 14 ]
  6. Percentage of subjects that are not admitted to the Intensive Care Unit (ICU) [ Time Frame: 14 Days ]
  7. 28-day mortality [ Time Frame: At Day 28 ]

Other Outcome Measures:
  1. Percent change in neutrophil count from baseline to Day 7 and 14 [ Time Frame: Baseline to Day 7 and baseline to Day 14 ]
  2. Percent change in total lymphocyte count from baseline to Day 7 and 14 [ Time Frame: Baseline to Day 7 and baseline to Day 14 ]
  3. Change from baseline to Day 7 and 14 for neutrophil-derived circulating free DNA (cf-DNA/NETs) [ Time Frame: Baseline to Day 7 and baseline to Day 14 ]
  4. Change from baseline to Day 7 and 14 for Cytokine TNF-α [ Time Frame: Baseline to Day 7 and baseline to Day 14 ]
  5. Change from baseline to Day 7 and 14 for cytokine IL-1β [ Time Frame: Baseline to Day 7 and baseline to Day 14 ]
  6. Change from baseline to Day 7 and 14 for cytokine IL-1RA [ Time Frame: Baseline to Day 7 and baseline to Day 14 ]
  7. Change from baseline to Day 7 and 14 for cytokine IL-6 [ Time Frame: Baseline to Day 7 and baseline to Day 14 ]
  8. Change from baseline to Day 7 and 14 for cytokine IL-8 [ Time Frame: Baseline to Day 7 and baseline to Day 14 ]
  9. Change from baseline to Day 7 and 14 for cytokine IL-10 [ Time Frame: Baseline to Day 7 and baseline to Day 14 ]
  10. Change from baseline to Day 7 and 14 for Lactate Dehydrogenase (LDH) [ Time Frame: Baseline to Day 7 and baseline to Day 14 ]
  11. Change from baseline to Day 7 and 14 for D-dimer [ Time Frame: Baseline to Day 7 and baseline to Day 14 ]
  12. Change from baseline to Day 14 for cytokine IL-18 [ Time Frame: Baseline to Day 14 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects may be enrolled in the study only if all the inclusion criteria are met.

  1. Male and female subjects, age 60 and older, or age 50 to < 60 with BMI ≥ 35.
  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. SpO2 ≥ 93% on room air at screening and baseline.
  8. Currently hospitalized ≤ 3 days at screening.
  9. PCR 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04594343


Contacts
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Contact: Augusto Mota, MD/PhD (55) 75 98123-6212 augustomota@clinicaamo.com.br
Contact: Wendy Cousin, PhD 510-224-4422 wendy@springresearch.foundation

Locations
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Brazil
ETICA Recruiting
Salvador, Bahia, Brazil, CEP 41830-492
Contact: Augusto Mota, MD/PhD    (55) 75 98123-6212    augustomota@clinicaamo.com.br   
Sponsors and Collaborators
ETICA
Spring Research Foundation
Investigators
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Principal Investigator: Augusto Mota, MD/PhD ETICA
Study Director: Wendy Cousin, PhD Spring Research Foundation
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Responsible Party: Augusto Mota, Principal Investigator, ETICA
ClinicalTrials.gov Identifier: NCT04594343    
Other Study ID Numbers: SPR-001-201
First Posted: October 20, 2020    Key Record Dates
Last Update Posted: November 30, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Disulfiram
Alcohol Deterrents
Acetaldehyde Dehydrogenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action