Decitabine for COVID-19 Pneumonia-ARDS Treatment: DART Trial
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Proportion of patients who are alive and free of respiratory failure at day 28
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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)
- •If childbearing age: agree to practice effective birth control from screening until at least 180 days after last dose
排除标准
- •Hematologic cytopenias: Absolute Neutrophil Count (ANC) <1500/mm3, Hgb<7.0 and/or platelets <100,000/mm3
- •Subjects receiving or enrolled in clinical trial for other investigational treatment for SARS- 2-CoV.
- •Active malignancy, solid tumors, and current or recent chemotherapy
- •Concomitant use of nonbiologic immunosuppressants (e.g. Janus Kinase (JAK) inhibitors, Bruton's Tyrosine Kinase (BTK) inhibitors)
- •Active HIV viremia, or any other uncontrolled secondary infection.
- •Concurrent immunomodulating biologics or use of Palifermin, Dipyrone, Deferiprone
- •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
- •Pregnant women or women who are breastfeeding
- •Any Condition, per opinion of PI that would affect subject safety and/or compliance
- •Prior hypersensitivity to decitabine
研究组 & 干预措施
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)
干预措施: Decitabine (Drug)
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)
干预措施: Placebo Saline (Other)
结局指标
主要结局
Proportion of patients who are alive and free of respiratory failure at day 28
时间窗: 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.
次要结局
- Safety as assessed by adverse events(Up to 6 weeks)
- Change in oxygenation index(Daily, up to 6 weeks)
- All-cause mortality at 28 days since randomization(Daily upto day 28)
- Percentage of change of clinical score based on World Health Organization 9-point scale at day 10 from randomization(Daily from randomization to day 10)
- Percentage of change of clinical score based on World Health Organization (WHO 9) COVID progression scale(Weekly while patient is in hospital, up to 6 weeks)
- Change in fraction of inspired oxygen(Up to day 29)
- Overall survival(Up to 6 weeks)
- Length of stay in hospital(Till hospital discharge, up to 6 weeks)
- Ventilator free days(Up to 6 weeks)
- Time to Polymerase chain reaction (PCR) negativity(Up to 6 weeks)
- Percentage of patients with National Early Warning Score 2 of 3 or more(Weekly while patient is in hospital, up to 6 weeks)