What is the mechanism of action of this treatment?

Decitabine, a DNA hypomethylating agent, is being studied for its potential to treat COVID-19-related acute respiratory distress syndrome (ARDS). DNA hypomethylation can reactivate suppressed genes that may help in modulating the immune response and reducing inflammation, which is crucial in managing severe COVID-19 cases. This matters for COVID-19 patients because controlling the hyperinflammatory response can prevent complications and improve outcomes. Broadly, common COVID-19 treatments include antiviral drugs that inhibit viral replication, immunomodulators that adjust the immune response, and supportive therapies to manage symptoms and prevent organ failure.

What side effects are associated with this type of intervention?

Common treatments for COVID-19, such as hydroxychloroquine, remdesivir, and interleukin-6 inhibitors, have been associated with various side effects. Hydroxychloroquine can cause cardiac arrhythmias, gastrointestinal disturbances, and retinal toxicity. Remdesivir may lead to liver enzyme elevations and gastrointestinal symptoms. Interleukin-6 inhibitors can result in increased risk of infections and liver enzyme abnormalities. Decitabine, a DNA hypomethylating agent being studied for COVID-19 ARDS, may cause myelosuppression, leading to anemia, neutropenia, and thrombocytopenia, as well as gastrointestinal symptoms like nausea and vomiting.

What prior FDA approvals exist?

The FDA has approved several treatments for COVID-19, including antiviral drugs like remdesivir and monoclonal antibodies such as bamlanivimab and casirivimab/imdevimab. While decitabine, a DNA hypomethylating agent, is being studied for its potential in treating COVID-19-related ARDS, there are no current FDA approvals for COVID-19 treatments specifically targeting DNA hypomethylation. The focus has primarily been on antivirals, monoclonal antibodies, and supportive care measures.

What other types of research exist?

Promising novel alternatives to Decitabine for COVID-19 patients include high-dose methotrexate with leucovorin rescue (HDMTX-LR) for immune stabilization and other agents under investigation such as antiviral drugs, monoclonal antibodies, and immunomodulators. These alternatives are being evaluated for their efficacy in preventing the progression of COVID-19 and improving clinical outcomes.

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Anti-metabolites

Decitabine for COVID-19 (DART Trial)

Phase 2

Waitlist Available

Led By Pali Shah, M.D

Research Sponsored by Johns Hopkins University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Use of Intermittent Mechanical Ventilation, non-invasive mechanical ventilation (NIMV) or High Flow Nasal Cannula

Have ARDS or Acute Lung Injury physiology confirmed by Pao2/Fio2 ratio of < 300

Must not have

Subjects with severe sepsis with vasopressors or extrapulmonary organ failure: Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) /alkaline phosphatase (ALK) Phos ≥3x upper limit of normal (ULN) and Total Bilirubin (TBILI) ≥2x ULN; or Creatinine clearance <30 mL/min

Concurrent immunomodulating biologics or use of Palifermin, Dipyrone, Deferiprone

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to day 29

Summary

This trial tests if the drug decitabine can safely and effectively treat severe lung issues in critically ill COVID-19 patients. Patients will receive either decitabine or standard care. The goal is to see if decitabine helps improve their condition by reducing lung damage.

Who is the study for?

This trial is for adults over 18 with severe COVID-19 and ARDS, using mechanical ventilation or high-flow oxygen. They must have a lab-confirmed SARS-CoV-2 infection and agree to use birth control if of childbearing age. Excluded are those with certain organ failures, active cancers, blood disorders, other experimental treatments for COVID-19, uncontrolled infections like HIV, pregnant or breastfeeding women.

What is being tested?

The DART Trial is testing the safety and effectiveness of Decitabine in treating critically ill COVID-ARDS patients. It's a Phase 2 study where participants get either Decitabine plus standard care or a saline placebo plus standard care. The main goal is to see if they improve on a clinical scale.

What are the potential side effects?

Decitabine can cause side effects such as low blood cell counts leading to increased infection risk, bleeding problems, fatigue; it may also affect liver function tests and could potentially cause allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I use a machine to help with my breathing.

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My lung function is severely impaired, as shown by a specific oxygen test.

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I have tested positive for COVID-19 through a lab test.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My liver enzymes or bilirubin levels are very high, or my kidneys are not working well.

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I am not currently taking any immune system modifying drugs or specific medications like Palifermin, Dipyrone, or Deferiprone.

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I am currently receiving or have recently received chemotherapy for my solid tumor cancer.

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I am not taking any nonbiologic immunosuppressants like JAK or BTK inhibitors.

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I do not have active HIV or any uncontrolled infections.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to day 29

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to day 29

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to day 29 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Proportion of patients who are alive and free of respiratory failure at day 28

Secondary study objectives

All-cause mortality at 28 days since randomization

Change in fraction of inspired oxygen

Change in oxygenation index

+8 more

Trial Design

2Treatment groups

Active Control

Placebo Group

Group I: Decitabine + Standard of Care (SOC)Active Control1 Intervention

Study drug Decitabine will be administered via Intravenous injection. Dosage Regimen: 10mg/m\^2/day IV day x 5 days (1 cycle only)

Group II: Standard of Care (SOC) + PlaceboPlacebo Group1 Intervention

Saline based placebo will be administered via Intravenous injection. Dosage Regimen: 10mg/m\^2/day IV day x 5 days (1 cycle only)

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Decitabine, a DNA hypomethylating agent, is being studied for its potential to treat COVID-19-related acute respiratory distress syndrome (ARDS). DNA hypomethylation can reactivate suppressed genes that may help in modulating the immune response and reducing inflammation, which is crucial in managing severe COVID-19 cases. This matters for COVID-19 patients because controlling the hyperinflammatory response can prevent complications and improve outcomes. Broadly, common COVID-19 treatments include antiviral drugs that inhibit viral replication, immunomodulators that adjust the immune response, and supportive therapies to manage symptoms and prevent organ failure.

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