DISulfiram for COvid-19 (DISCO) Trial
关键词
抽象
描述
The identification of a safe, effective treatment for individuals with early mild-to-moderate symptomatic COVID-19 that prevent progression to more severe disease would have immediate public health implications. A hallmark of severe COVID-19 disease is immune system dysregulation called cytokine storm. Multiple studies have reported that patients with severe disease demonstrate elevated levels of pro-inflammatory cytokines early in disease, and elevated IL-6 plasma concentrations are predictive of poor clinical outcomes in COVID-19. Disulfiram, an FDA-approved drug for the treatment of alcohol dependence disorder is an appealing therapeutic option for COVID-19. It has a good safety profile, easy dosing schedule, and recent data suggesting multiple mechanisms by which disulfiram may act on COVID-19 (both as a direct antiviral agent as well as indirect effects on reducing inflammation). In addition disulfiram has been studied extensively with detailed available pharmacokinetic data; disulfiram has a short half-life ~7.5 hours with >90% of drug eliminated within 3 days post-dose, allowing quick reversal of any potential adverse effects. This is a randomized, placebo-controlled assessment of disulfiram in people with early mild-to-moderate symptomatic COVID-19. Disulfiram 2 grams or a placebo will be administered orally once daily for 3 consecutive days. Sixty (N=30 mild, N= moderate/severe) symptomatic COVID PCR+ participants will be randomized (1:1) to receive active drug versus placebo. Subsequent stratified analyses will be performed based on upper limit of normal hs-CRP, ferritin, D-dimer levels. Drug/placebo will be administered using strict infection control protocols designed to support the study of people with acute COVID-19 infection per the Center for Diseases Control (CDC) guidelines (https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-in-home-patients.html).
日期
| 最后验证: | 06/30/2020 |
| 首次提交: | 07/21/2020 |
| 提交的预估入学人数: | 07/21/2020 |
| 首次发布: | 07/23/2020 |
| 上次提交的更新: | 07/21/2020 |
| 最近更新发布: | 07/23/2020 |
| 实际学习开始日期: | 08/31/2020 |
| 预计主要完成日期: | 05/31/2021 |
| 预计完成日期: | 08/31/2021 |
状况或疾病
干预/治疗
Drug: Disulfiram
Drug: Placebo
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Experimental: Disulfiram This study will provide open label disulfiram. Participants will take 2 grams (4 x 500mg tablets) of disulfiram per day for a total of 3 days. | Drug: Disulfiram This study will provide open label disulfiram. Participants will take 2 grams (4 x 500mg tablets) of disulfiram per day for a total of 3 days. |
| Placebo Comparator: Placebo This study will provide placebo comparator for disulfiram. Participants receiving placebo will take 4 tablets of placebo per day for a total of 3 days. | Drug: Placebo This study will provide placebo. Participants will take 4 tablets of placebo per day for a total of 3 days. |
资格标准
| 有资格学习的年龄 | 18 Years 至 18 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria: - Willing and able to provide written informed consent, and - Age >= 18 years, and - SARS-CoV-2 positive PCR (nucleic acid) test within the preceding 7 days, and - Not currently hospitalized, and - Willing to abstain from any alcohol during the two week period in which disulfiram will be administered and during the two week period immediately after disulfiram administration. - Both male and female subjects are eligible. Females of childbearing potential must have a negative pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period. Exclusion Criteria: - Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study - Active malignancy requiring systemic chemotherapy or surgery in the preceding 3 months or for whom such therapies are expected in the subsequent 6 months - Decompensated liver disease as defined by the presence of ascites, encephalopathy, esophageal or gastric varices, or persistent jaundice - Serious illness requiring systemic treatment and/or hospitalization in the 3 months prior to study enrollment - Concurrent treatment with immunomodulatory drugs, and/or exposure to any immunomodulatory drug in the 4 weeks prior to study enrollment (e.g. corticosteroid therapy equal to or exceeding a dose of 15 mg/day of prednisone for more than 10 days, IL-2, interferon-alpha, methotrexate, cancer chemotherapy). NOTE: use of inhaled or nasal steroid is not exclusionary. - Serious medical or psychiatric illness that, in the opinion of the site investigator, would interfere with the ability to adhere to study requirements or to give informed consent. - Current alcohol use disorder or hazardous alcohol use (>7 drinks per week for women or > 14 drinks per week for men) as determined by clinical evaluation. - Current use of any drug formulation that contains alcohol or that might contain alcohol - Current use of warfarin. - Clinically active hepatitis determined by the study physician; ALT or AST > 3 x the upper limit of normal or total bilirubin outside the normal range. - Allergy to rubber or thiuram derivatives |
结果
主要结果指标
1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [31 days]
2. Change in COVID-19 symptom severity score as assessed by a 5-point adapted somatic symptom severity score (SSS-8) [31 days]
次要成果指标
1. Virologic impact of 3 days of disulfiram, as measured by the fold-change in copies of SARS-CoV-2 virus per million cells between Baseline and Day 31. [31 days]
2. Immunologic impact of 3 days of disulfiram, as measured by the fold-change in plasma levels of pro-inflammatory cytokines (e.g, interleukin 6, interleukin 1-beta, etc.). [31 days]
