Safety and Efficacy of Intravenous Infusion of Wharton's Jelly Derived Mesenchymal Stem Cell Plus Standard Therapy for the Treatment of Patients With Acute Respiratory Distress Syndrome Diagnosis Due to COVID 19: A Randomized Controlled Trial
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Intergroup mortality difference with treatment
研究概览
简要总结
Recent COVID 19 pandemic has overwhelmed health services all around the world, and humanity has yet to find a cure or a vaccine for the treatment of patients, mainly the severe ones, who pose a therapeutic challenge to healthcare professionals given the paucity of information we have regarding SARS-CoV-2 pathogenesis.
Recently, reports mainly from China from patients treated with mesenchymal stem cells have shown promise in accelerating recovery, even in the critically ill and the therapy has sustained an increase in research because of it's powerful immunomodulatory effects, making it and interesting alternative in patients with lung and systemic inflammation.
These effects could help treat a lot of patients and improve their outcomes, reason why phase I/II studies are needed to show their safety and experimental efficacy.
详细描述
SARS-CoV-2, virus culprit of the COVID 19 that emerged in China, has become now a worldwide problem, with more than three million cases al around the world as reported by the World Health Organization. This situation has put health systems under extreme pressure, being overwhelmed be the amount of patients requiring attention.
Around 5% of patients will require ICU internation, due to severe lung inflammation giving rise to Acute Respiratory Distress Syndrome (ARDS) and a cytokine storm that ultimately affects other organs. In this group, mortality can be as high as 40%.
Mesenchymal stem cells (MSC) have shown great immunomodulatory effects, and are used in other inflammatory conditions as autoimmune diseases, being safe and preliminary effective in improving patients health status. They exert their effect via paracrine and autocrine pathways and have been shown to reduce IL-1, IL-6, Tumor necrosis factor alpha and increase IL-10 in COVID 19 patients. One of the greater advantages of the MSC is that they express no Major Histocompatibility Complex, reducing the risk of host immune reaction.
Given their immunomodulatory effects, research in this topic showing their safety and experimental efficacy are needed, as therapies for severe patients are lacking. Patients, researchers and data analysts will be blinded, and ARDS patients will be randomly allocated in standard therapy plus MSC arm or standard therapy alone to answer these questions.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Patient code will be stored in sealed, opaque envelops with their respective codification. These envelops will be stored in Clinica Somer's Research Unit and the only person with access permission will be the pharmaceutical chemist in charge. Treatment delivery (MSC or placebo) will also be in charge of the chemist, guaranteeing blinding of patient and healthcare professionals. Data analysis will be done by people blind to the treatment received by each patient.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •SARS-CoV-2 positive Real Time - Polymerase Chain Reaction
- •Moderate to severe Acute respiratory distress syndrome according to Murray classification.
- •PaO2/FiO2 less than 200 mmHg.
- •Within 36 hours of orotracheal intubation.
- •Absence of response with previous standard therapy.
- •Willing to participate in the study expressed by patient or responsible caregiver.
- •Not being in other clinical trial.
排除标准
- •Current pregnancy.
- •Cardiac rhythm abnormalities with instability.
- •Acute congestive heart failure/cardiogenic shock.
- •Severe comorbidities affecting mortality as defined by research group.
- •Cancer history in the past 5 years.
- •HIV, syphilis, hepatitis B or C.
- •Concomitant use of immunosuppressive therapy with contraindication to MSC.
- •Fivefold elevation of liver enzymes (ALT, AST).
- •Chronic kidney disease with glomerular filtration rate below 30ml/min or dialytic needs.
研究组 & 干预措施
Mesenchymal stem cell
WJ MSC 50*10e6, two doses plus standard treatment with hydroxychloroquine + Lopinavir/Ritonavir or Azithromycin and ventilation support.
干预措施: Wharton's jelly derived Mesenchymal stem cells. (Drug)
Control group
Hydroxychloroquine, lopinavir/ritonavir and ventilation support plus placebo
干预措施: Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy) (Drug)
结局指标
主要结局
Intergroup mortality difference with treatment
时间窗: 28 days.
Evaluation of efficacy of WJ-MSC defined by mortality at 28 days of application.
次要结局
- Median reduction of days of hospitalization(From hospital admission to 180 days.)
- Number of patients with treatment related adverse events(6 months.)
- Difference in days of mechanical ventilation between groups(From ICU admission to 180 days.)
- Median reduction of days of oxygen needs(From hospital admission to 180 days.)
- Difference between "Sequential Organ Failure Assessment" score between groups(Baseline to 7 days)
- Difference in lymphocyte count between groups(baseline and 21 days or discharge)
- Difference between median Murray score between groups(Baseline and 7 days)
- Difference in APACHE II score between groups(Baseline and 7 days)
- Impact on interleukin 6 concentrations between groups.(Baseline and 7 days)
- Impact on interleukin 10 concentrations between groups.(Baseline and 7 days)
- Changes in C reactive protein concentration between groups(baseline and 21 days or discharge)
- Changes in D dimer concentration(baseline and 21 days or discharge)
- Changes in ferritin concentration(baseline and 21 days or discharge)
- Changes in lactate dehydrogenase concentration(baseline and 21 days or discharge)
- Impact on interleukin 8 concentrations between groups.(Baseline and 7 days)
- Impact on tumor necrosis factor alpha concentrations between groups.(Baseline to 7 days.)