Decitabine for Coronavirus (COVID-19) Pneumonia- Acute Respiratory Distress Syndrome (ARDS) Treatment: DART Trial (DART)

March 27, 2024 updated by: Johns Hopkins University

Decitabine for COVID-19 Pneumonia-ARDS Treatment: DART Trial

This is a a randomized double blind placebo controlled Phase 2 trial with a 12 patient lead-in to evaluate safety, prior to full enrollment to an additional 28 patients (for a total of 40 patients) to assess efficacy of decitabine in the treatment of critically ill patients with COVID-ARDS. The patients will be randomized in a 1:1 ratio to receive standard of care plus Decitabine or standard of care plus saline based placebo. The primary objective is to determine safety and efficacy of decitabine for COVID-19 ARDS based on clinical improvement on a 6-point clinical scale.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a randomized double blind placebo controlled Phase 2 trial with a 12 patient lead-in to evaluate safety, prior to full enrollment to an additional 28 patients (for a total of 40 patients) to assess efficacy of decitabine in the treatment of critically ill patients with COVID-ARDS. The patients will be randomized in a 1:1 ratio to receive standard of care plus Decitabine or standard of care plus saline based placebo.

Eligible patients will receive decitabine 10 mg/m2 daily for 5 days, 1 cycle only. This is a dose that is half the FDA approved dose for myelodysplastic syndrome (MDS), and using a single cycle.

If less than 2 of the first 6 (treatment arm) patients experience an unacceptable toxicity, defined as any treatment related grade III or higher adverse events, as per section 5.7, within 15 days of initiation of treatment, the drug is safe to continue. If the investigators observe more than 33% patients with unacceptable toxicity, the investigators will pause the accrual pending safety evaluation. After validating safety, the investigators will enroll additional 28 patients towards the primary efficacy endpoint. The investigators will monitor safety throughout the trial by monitoring clinical hematologic, chemistry, vital signs, respiratory parameters, medications, and clinical changes daily as per the schedule of procedures.

Bio samples from peripheral blood mononuclear cell (PBMC) and Mini Bronchoalveolar lavage (BAL) will be collected and stored for secondary analysis and mini BAL will only be collected as an optional sub-study for patient consented to a separate study protocol either at time-point of for-cause clinically indicated bronchoscopy, or for subjects consented to a separate Bronchoalveolar lavage (BAL) interventional study, under the auspices of that protocol. For research bio specimens required after study drug initiation, a window period of +/-24 hours while inpatient, and +/- 4 days for outpatient monitoring will be permitted.

These objectives will allow for the planning of subsequent phase 3 studies, and strengthen implementation of a multi-center randomized trial should this study confirm safety, and suggest efficacy of therapy.

Study Type

Interventional

Enrollment (Actual)

33

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. ≥18 years
  2. Use of Intermittent Mechanical Ventilation, non-invasive mechanical ventilation (NIMV) or High Flow Nasal Cannula.
  3. Have ARDS or Acute Lung Injury physiology confirmed by Pao2/Fio2 ratio of < 300
  4. Severe Acute Respiratory Distress Syndrome (SARS) - Coronavirus (CoV-2) determined by lab polymerase chain reaction assay in either upper or lower respiratory tract sampling (e.g. bronchoalveolar lavage or nasopharyngeal swab)
  5. If childbearing age: agree to practice effective birth control from screening until at least 180 days after last dose

Exclusion Criteria:

  1. Hematologic cytopenias: Absolute Neutrophil Count (ANC) <1500/mm3, Hgb<7.0 and/or platelets <100,000/mm3
  2. Subjects receiving or enrolled in clinical trial for other investigational treatment for SARS- 2-CoV.
  3. Active malignancy, solid tumors, and current or recent chemotherapy
  4. Concomitant use of nonbiologic immunosuppressants (e.g. Janus Kinase (JAK) inhibitors, Bruton's Tyrosine Kinase (BTK) inhibitors)
  5. Active HIV viremia, or any other uncontrolled secondary infection.
  6. Concurrent immunomodulating biologics or use of Palifermin, Dipyrone, Deferiprone
  7. Subjects with severe sepsis with vasopressors or extrapulmonary organ failure:
  8. 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
  9. Pregnant women or women who are breastfeeding
  10. Any Condition, per opinion of PI that would affect subject safety and/or compliance
  11. Prior hypersensitivity to decitabine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Decitabine + Standard of Care (SOC)
Study drug Decitabine will be administered via Intravenous injection. Dosage Regimen: 10mg/m^2/day IV day x 5 days (1 cycle only)
Drug: Decitabine

Study duration is 6 weeks after the last dose of study drug. Number of study visits is dependent on Length of hospitalization of study participant. Study visits are scheduled on days 0-7, 11, 15, 29, and may occur via telemedicine or inpatient assessment or outpatient assessment in COVID recovered participants.

Decitabine will be administered via Intravenous Administration 10/mg/m^2/day Dosage: 10mg/m^2/day IV day x 5 days (1 cycle only)

Other Names:
  • DACOGEN
  • 5-aza-2'- deoxycytidine
Placebo Comparator: Standard of Care (SOC) + Placebo
Saline based placebo will be administered via Intravenous injection. Dosage Regimen: 10mg/m^2/day IV day x 5 days (1 cycle only)
Other: Placebo Saline
Saline based placebo will be administered via Intravenous injection. Dosage Regimen: 10mg/m^2/day IV day x 5 days (1 cycle only)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients who are alive and free of respiratory failure at day 28
Time Frame: From the day of randomization to day 28
The proportion of patients who are alive and free of respiratory failure at day 28 since start of randomization.
From the day of randomization to day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety as assessed by adverse events
Time Frame: Up to 6 weeks
Safety assessments using adverse events will be monitored daily while inpatient and weekly through end of study at week 6 once discharged from hospital. They will be monitored and graded using Common Terminology Criteria Adverse Events version 5.0.
Up to 6 weeks
Change in oxygenation index
Time Frame: Daily, up to 6 weeks
Oxygenation index is used to assess severity of hypoxic respiratory failure. (OI = mean airway pressure (MAP) × Fraction of inspired oxygen (FiO2) × 100÷ partial pressure of oxygen (PaO2). This will be measured daily while subject is on mechanical ventilation up to 6 weeks.
Daily, up to 6 weeks
Change in fraction of inspired oxygen
Time Frame: Up to day 29
Fraction of inspired oxygen in the oxygen delivery system during hospital stay. Measured at 8 am daily during hospital stay and then weekly until day 29.
Up to day 29
Overall survival
Time Frame: Up to 6 weeks
Patients status of alive versus death at completion of study follow up period, i.e. 6 weeks from start.
Up to 6 weeks
Length of stay in hospital
Time Frame: Till hospital discharge, up to 6 weeks
Duration of days from baseline to hospital discharge.
Till hospital discharge, up to 6 weeks
Ventilator free days
Time Frame: Up to 6 weeks
For subjects who received mechanical ventilation, total number of days from baseline to end of study at 6 weeks that subject was not on mechanical or non invasive mechanical ventilation.
Up to 6 weeks
Time to Polymerase chain reaction (PCR) negativity
Time Frame: Up to 6 weeks
If viremic at starting date of decitabine - time from baseline to 1st recorded negative COVID nucleic acid amplification (NAT) based assay, measured in days.
Up to 6 weeks
Percentage of patients with National Early Warning Score 2 of 3 or more
Time Frame: Weekly while patient is in hospital, up to 6 weeks
Determines the degree of illness of a patient and prompts critical care intervention. This composite score includes Respiratory Rate, Temperature, oxygen Saturation, Blood Pressure, Oxygen inspired and cognitive status. This will be measured at baseline and weekly while patient is in hospital.
Weekly while patient is in hospital, up to 6 weeks
All-cause mortality at 28 days since randomization
Time Frame: Daily upto day 28
Total number of death at 28 days since day of randomization
Daily upto day 28
Percentage of change of clinical score based on WHO 9-point scale
Time Frame: Weekly while patient is in hospital, up to 6 weeks
11. Time from randomization to an at least 2-point decrease in clinical score based on WHO 9-point scale
Weekly while patient is in hospital, up to 6 weeks
Percentage of change of clinical score based on World Health Organization 9-point scale at day 10 from randomization
Time Frame: Daily from randomization to day 10
Determine clinical score from randomization date to day 10
Daily from randomization to day 10

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Investigators

  • Principal Investigator: Franco D'Alessio, M.D, Johns Hopkins UIniversity

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 14, 2020

Primary Completion (Estimated)

September 1, 2024

Study Completion (Estimated)

March 1, 2025

Study Registration Dates

First Submitted

July 21, 2020

First Submitted That Met QC Criteria

July 21, 2020

First Posted (Actual)

July 22, 2020

Study Record Updates

Last Update Posted (Actual)

March 28, 2024

Last Update Submitted That Met QC Criteria

March 27, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00247544

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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