Double Blind, Placebo-controlled, Phase I/II Clinical Trial to Evaluate Safety and Efficacy of Allogeneic Mesenchymal Stem/Stromal Cells MSV-allo for Treatment of Acute Respiratory Failure in Patients With COVID-19 Pneumonia (MSV-COVID)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Proportion of patients in whom removal of invasive mechanical ventilation (IMV) has been achieved
研究概览
简要总结
Novel coronavirus disease COVID-19, produced by SARS-CoV-2, has become a health emergency around the world. Since first patients were detected in Wuhan (China), in December 2019, COVID-19 has spread quickly worldwide, being a severe threat to public health. Fever, dry cough, shortness of breath and breathing distress are the main characteristics of COVID-19 infection. Some patients develop overwhelming lung inflammation and acute respiratory failure, for which there is no specific therapy. Therefore, safe and effective treatment for COVID-19 pneumonia is utterly necessary, mainly in critical cases. Mesenchymal stem/stromal cells (MSCs) have been widely used in the immune-mediated inflammatory diseases. MSCs can regulate both innate and adaptive immunity by suppressing the proliferation, differentiation and activation of different cells. These immunomodulatory properties of MSCs support performance of the double-blind, placebo-controlled, randomized, phase I/II clinical trial to evaluate safety and efficacy of allogeneic MSCs for treatment of severe COVID-19 pneumonia.
详细描述
Novel coronavirus disease COVID-19, produced by SARS-CoV-2, has spread quickly from Wuhan (China) to worldwide. On April 15, 2020, the World Health Organization (WHO) has reported 1.914.916 confirmed cases and 123.010 deaths globally, being a severe threat to public health.
Some patients develop overwhelming lung inflammation and acute respiratory failure. Several reports demonstrated that SARS-CoV-2 specifically recognize the angiotensin I converting ezyme 2 receptor (ACE2) and ACE2-positive cells are infected by the virus. ACE2 receptor is widely present on the human cells surface such as alveolar type II cells and capillary endothelium, among others. SARS-CoV-2 infects cells and stimulates a terrible cytokine storm in the lung followed by edema, dysfunction of the air exchange and acute respiratory distress which may lead to death. Further, once SARS-CoV-2 enters in blood circulation, it can easily spread to some systems and organs, causing significant damage. Under these circumstances, it is reasonable to believe that the inhibition of inflammatory response is the key to treat COVID-19 pneumonia.
Mesenchymal stem/stromal cells (MSCs) have been widely used in the immune-mediated inflammatory diseases. MSCs can regulate both innate and adaptive immunity by suppressing the proliferation, differentiation and activation of different cells. Some studies have shown that MSCs can significantly reduce acute lung injury in mice caused by H9N2 and H5N1 viruses, reducing proinflammatory cytokines and inflammatory cells into the lungs.
These immunomodulatory properties of MSCs support performance of the placebo-controlled, double-blind (neither the participant nor the investigator will know if active drug or placebo is assigned), randomized (assigned by chance), phase I/II clinical trial in which subjects with severe COVID-19 pneumonia will receive either MSCs (1 million cells/kg) or placebo by intravenous injection. The administration of cells will be done only once.
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
Both experimental and placebo groups will receive a similar endovenous injection with either cells or placebo, respectively. Blind to participant, investigator and care providers.
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
- •Women or men of ≥ 18 years of age
- •SARS-CoV-2 infection confirmed by molecular testing.
- •Admitted to the Intensive Care Unit with pneumonia by COVID-19 infection and intubated in the last 48 hours, that meet at least one of these criteria:
- •Respiratory distress.
- •Respiratory rate (RR) ≥ 30 rpm.
- •Basal oxygen saturation at rest ≤ 93%.
- •Arterial partial pressure of oxygen (PaO2) / inspiratory fraction of oxygen (FiO2) ≤ 300 mmHg.
- •Consent of the patient or his/her legal representative for participation in the study.
排除标准
- •Active tumor disease.
- •Participation in another active clinical trial.
- •Any circumstance that in the researcher's opinion justifies the patient's non-participation in the trial.
- •Not consent to participation.
结局指标
主要结局
Proportion of patients in whom removal of invasive mechanical ventilation (IMV) has been achieved
时间窗: 0-7 days
Index of therapy success to preserve Intensive Care Unit (ICU) space.
Overall survival
时间窗: 0-28 days
To measure global success
次要结局
- Complete clinical response(0-Event/Loss to follow-up)
- Complete radiological response(0-28 days)
- Radiological improvement of pulmonary images(0-5 days)
- Removal of invasive mechanical ventilation (IMV)(0-28 days)