Study to AntagOnize Plasminogen Activator Inhibitor-1 in Severe COVID-19 (STOP Severe COVID-19)
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Clinical improvement
研究概览
简要总结
This is a single-center, randomized double blind placebo controlled trial to evaluate the efficacy and safety of novel PAI-1 inhibitor (TM5614) for high-risk patients hospitalized with severe COVID-19 at Northwestern Memorial Hospital. The patients will be randomized in a 1:1 ratio to receive standard of care plus TM5614 or standard of care plus placebo.
详细描述
This project will evaluate the efficacy and safety of a novel small molecule therapy targeting PAI-1 (TM5614) for patients with severe COVID-19. This is a randomized (1:1), double-blinded trial that will enroll adult patients (> 65 years OR <65 years with at least one major cardiometabolic comorbidity [diabetes, hypertension, or cardiovascular disease]) with COVID-19 requiring supplemental oxygen. The study intervention will be a small molecule inhibitor of PAI-1, TM5614, up to 180 mg, compared to matching placebo for up to 7 days.
Research blood samples for PAI-1 and C-reactive protein (CRP) will be collected at time of enrollment, 48 hours after 1st dose of medication and at day 7 or discharge, whichever comes first.
These objectives will allow for the planning of subsequent phase 3 study, 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
- Triple (Participant, Care Provider, Investigator)
盲法说明
double-blind, randomized (1:1)
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
- •Adults ≥65 years old or < 65 years old AND at least one major cardiometabolic comorbidity (diabetes, hypertension, or cardiovascular disease)
- •Established diagnosis of COVID-19 as evidenced by a positive nasopharyngeal or bronchoalveolar lavage viral PCR for SARS-CoV2
- •Requiring supplemental oxygen
排除标准
- •Age <18 years old
- •Pregnancy or breast-feeding
- •Known contraindication to tissue plasminogen activator (tPA), including
- •Active internal bleeding
- •History of cerebrovascular accident
- •Recent intracranial or intraspinal surgery or trauma
- •Intracranial neoplasm, arteriovenous malformation or aneurysm
- •Known bleeding diathesis
- •Severe uncontrolled hypertension (SBP>200 persistently >12 hours)
- •Currently receiving therapeutic dose anticoagulation (specifically will exclude those with potential drug-drug interaction such as heparin, apixaban, warfarin)
- •Platelets <50,000
- •Hematocrit <30%
- •Not hemodynamically stable in the preceding 4 hours (symptomatic hypotension or systolic BP <95 mmHg at 2 out of 3 measurements)
- •Concomitant illness, physical impairment or mental condition which in the opinion of the study team / primary care physician could interfere with the conduct of the study including outcome assessment
- •Other patient characteristics (not thought to be related to COVID-19) that portend a very poor prognosis (e.g., severe liver failure, metastatic malignancy)
- •Participation in a concurrent interventional medical investigation or pharmacologic clinical trial. Patients in observational, natural history or epidemiological studies not involving an intervention are eligible.
- •Participant's responsible attending physician believes it is not appropriate for participant to participate in the study.
- •Inability or unwillingness to provide written informed consent
- •Involvement in the planning and/or conduct of the study
- •Previous randomization in the present study
- •Unable to complete study procedures.
- •Patients with active venothromboembolic disease
- •Patients who are receiving other investigational agents for COVID-19.
研究组 & 干预措施
TM5614
TM5614 30 mg tablets. 6 tablets (180 mg) taken by mouth, once daily for up to 7 days
干预措施: TM5614 (Drug)
Placebo
Placebo tablets. 6 tablets taken by mouth, once daily for up to 7 days
干预措施: Placebo (Other)
结局指标
主要结局
Clinical improvement
时间窗: 7 Days
Change of at least 2 points in the NIAID-defined ordinal scale (higher scores indicate improved outcome),: 1. Death 2. Hospitalized, receiving invasive mechanical ventilation or ECMO 3. Hospitalized, receiving noninvasive ventilation or high-flow oxygen devices 4. Hospitalized, requiring low-flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen but receiving ongoing medical care (related or not related to Covid-19) 6. Hospitalized, requiring neither supplemental oxygen nor ongoing medical care (other than that specified in the protocol) 7. Not hospitalized
次要结局
- Sequential organ failure assessment (SOFA) score change(7 Days)
- PAI-1 Levels(48 hours)
- Ventilator free days(14 days)
研究者
Sanjiv Shah
Director of Research, Bluhm Cardiovascular Institute
Northwestern University