Two Phases Clinical Trial to Evaluate Safety and Efficacy of Methotrexate Associated to LDL Like Nanoparticles (LDE-MTX) in the Treatment of Patients With Mild Coronavirus-19 (COVID-19) Disease.
试验速览
- 阶段
- 1 期
- 入组人数
- 100
- 试验地点
- 3
- 主要终点
- Duration of hospital stay
研究概览
简要总结
The investigators propose a prospective, randomized, double-blind, placebo-controlled study, conducted in two phases. The purpose of the study is to evaluate the safety and efficacy of methotrexate in a cholesterol-rich non-protein nanoparticle (MTX -LDE) in adults diagnosed with mild Coronavirus-19(COVID-19) disease.
A total of 100 patients will be randomized to receive MTX-LDE or placebo each 7 days, up to 3 times, during in hospital treatment.
详细描述
The objective of the study is to evaluate the safety and efficacy of (MTX -LDE) in patients with mild Coronavirus-19 (COVID-19) disease.
In phase 1, firstly 3 patients with moderate COVID-19 disease will receive MTX-LDE IV 15mg each 7 days, up to 3 times, during hospitalization. After that, 9 patients with moderate COVID-19 disease will receive MTX-LDE IV 30mg each 7 days, up to 3 times, during hospitalization. Follow-up assessments will occur daily following randomization during in hospital treatment and 2 weeks after discharge for evaluation of the occurrence of adverse events.The purpose of this phase will be evaluate safety and pharmacokinetics.
If no objection by data and safety monitoring board (DSMB), will be authorized to start the second phase.
In phase 2, 88 patients with moderate COVID-19 disease will be randomized to receive MTX-LDE IV 30mg or placebo-LDE IV each 7 days, up to 3 times, during hospitalization. Follow-up assessments will occur daily following randomization during in hospital treatment and 2 weeks after discharge for evaluation of the occurrence of any trial endpoints or other adverse events.The primary endpoint of this phase will be reduction in duration of hospitalization stay between groups.
Patients will undergo clinical and laboratory safety evaluations daily. An algorithm for drug suspension based on clinical and laboratory finding will be followed.
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, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who were hospitalized with confirmed COVID-19
- •Mild Coronavirus-19 disease (WHO Coronavirus-19 scale < 5)
- •Fewer than 14 days since symptom onset.
- •Female patient is not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile.
- •Female patient is of childbearing potential must has a negative pregnancy test.
- •Signing the study informed consent.
排除标准
- •Need for oxygen supplementation >4 L/min via nasal cannula or ≥40% via Venturi mask.
- •Need for oxygen supplementation via high-flow nasal cannula.
- •Need for invasive mechanical ventilation.
- •Extent of pulmonary involvement > 50% by CT scan.
- •Chronic renal failure (estimated glomerular filtration rate <30 mL/min/1.73 m2)
- •History of liver cirrhosis (Bilirubins levels > 3mg/dl)
- •History of heart failure ( Ejection fraction <40%)
- •History of Steven-Johnson disease
- •History of stroke in the last 6 months
- •History of sickle cell disease
- •Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers.
- •Prior history of chronic hepatitis B or C infection and known HIV positive.
- •Patient undergoing chemotherapy for cancer
- •Sepsis caused by fungal or multidrug resistant gram-negative bacteria
- •Known allergy to methotrexate.
- •Body mass index(BMI) > 40 or <18.5
- •Pregnancy or breastfeeding.
- •Patients enrolled in other clinical trials in the last 12 months
- •Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
研究组 & 干预措施
MTX-LDE phase 1
Methotrexate carried by a lipid nanoparticle (MTX-LDE)
干预措施: Methotrexate-LDE phase 1 (Drug)
MTX-LDE phase 2
Methotrexate carried by a lipid nanoparticle (MTX-LDE)
干预措施: Methotrexate-LDE phase 2 (Drug)
Placebo-LDE phase 2
Lipid nanoparticle (LDE)
干预措施: Placebo-LDE phase 2 (Drug)
结局指标
主要结局
Duration of hospital stay
时间窗: 30 days after randomization
Compare the duration of hospital stay between groups
次要结局
- Other adverse events(30 days after randomization)
- Sequential Organ Failure Assessment (SOFA) score(Baseline and change from baseline to 15 days after randomization)
- Number of participants requiring mechanical ventilation(15 days after randomization)
- Chest CT scan(Baseline and change from baseline to 15 days after randomization)
- Interleukin 6 (IL-6)(Baseline and change from baseline to 15 days after randomization)
- Number of participants requiring renal replacement therapy(15 days after randomization)
- World Health Organization (WHO) COVID-19 score(Baseline and change from baseline to 15 days after randomization)
- Dimer-D(Baseline and change from baseline to 15 days after randomization)
- Clinical side effects(30 days after randomization)
- Incidence of secondary infection(15 days after randomization)
- Number of participants requiring vasoactive drugs(15 days after randomization)
- Incidence and severity of laboratory alterations(30 days after randomization)
研究者
Raul Cavalcante Maranhão
MD; PHD. Director Lipid Metabolism Laboratory, Heart Institute
University of Sao Paulo General Hospital