Prospective, Randomized Phase 2 Clinical Trial of Mesenchymal Stem Cells(MSCs) for the Treatment of Coronavirus Disease 2019(COVID-19)
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
Since the outbreak of coronavirusdisease2019(COVID-19), many researchers in China have carried out/published clinical trials on treatment based on Western medicine, traditional Chinese medicine or a combination of the two. Trials on treatment modalities have mainly used antivirals, interferon, glucocorticoids in addition to traditional Chinese medicine. There are also clinical trials exploring hydroxyquinoline/chloroquine sulphate, immunoglobulins, Vitamin-C, washed microbiota, nebulized interferon, teicoplanin as well as Mesenchymal stem cells. However, most of these trials were small (median sample size 100) and the bulk of potential therapeutic strategies remain in the experimental phase and currently there is no effective specific antiviral with high-level evidence.The aim of this study is assess the efficacy of MSCs as an add-on therapy to standard supportive treatment for patients with moderate/severe COVID-19.
详细描述
All patients will receive 2x10^6 cells/kg on days 1 and day 7 (if needed). The study will be divided in 2 phases. In the first phase, 10 patients will be included and randomized to 2 groups (5 Treatment arm; 5 Control Arm) and receive 2 x10^6 cells/kg MSCs on days 1 and 7 in addition to standard care. Thereafter, the trial committee will meet and evaluate all collected safety and efficacy information to decide about crossover of Control arm to treatment arm if patient deteriorates clinically while in Control arm. Then, 10 new subjects will be included in the study and treated according to protocol.
Preparation of MSCs doses MSCs will be isolated from bone marrow harvested cells. About 50ml bone marrow will be collected from iliac crest using aseptic technique in syringes primed with anticoagulant. The collected sample will be diluted with Phosphate Buffer Saline (PBS) and MSCs will be separated using density gradient centrifugation. After resuspension the cells will be seeded at a fixed concentration of 100,000 cells/cm2 in specially designed flasks and incubated at 37oC in 5% carbondioxide (CO2). Medium will be changed after every third day till harvesting of MSCs from the flasks. Once confluent (approximately day 20) the cells will be harvested with sterile techniques using Trypsin- Ethylenediaminetetraacetic acid ( EDTA ) solution. The prepared cells can either be stored in 50ml cryogenic vials for future use or infused immediately.
Patient Selection and MSCs demand Patient for MSCs and Control arm will be selected by multidisciplinary team (MDT) comprising Critical Care Specialist, Pulmonologist, Infectious Disease Specialist, Clinical Hematologist.
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Demand for MSCs will be initiated on pre-designated forms , signed by Critical care Specialist Clearly indicating indication of MSCs.
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Request form will be sent Stem Cell Lab.
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Incharge stem Cell Lab will authorize issuance of the MSCs dose.
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Stem Cell Lab will issue the dose Administration of MSCs
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Experimental arm: Frozen MSCs will be resuspended in 100ml normal saline for immediate use and given intravenously. The patients should be pre-medicated to avoid allergic reactions to third party MSCs. Each patient in Experimental arm will be given 2 x 106 cells/kg will be administered on day 1,7 in addition to supportive care 2. Control Arm: Will be Continued on supportive care
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
- None
入排标准
- 年龄范围
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged ≥ 10years
- •Laboratory confirmation of COVID19 infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source; and
- •Moderate illness: In compliance with the 2019-coronavirus pneumonia diagnosis standard [according to the novel coronavirus infection pneumonia diagnosis and treatment program (Trial Implementation Version 6) issued by the National Health and Medical Commission, and world health organization (WHO) 2019 new coronavirus guidelines standards]: (A) increased breathing rate (≥30 beats / min), difficulty breathing, cyanosis of the lips; (B) in resting state, means oxygen saturation ≤93%; (C) partial pressure of arterial oxygen (PaO2) / Fraction of inspired oxygen (FiO2) ≤300 mmHg (1mmHg = 0.133kPa);
- •Critically ill : Respiratory failure, Septic Shock, muti-organ dysfunction syndrome (MODS)
排除标准
- •Patients with systemic autoimmune diseases
- •Not consenting for clinical trial
- •Those declared not for resuscitation due to underlying comorbid or current critical condition
研究组 & 干预措施
Placebo
Only supportive care will be given to 10 patients
干预措施: Placebo (Other)
Mesenchymal stem cells
10 patients will be given mesenchymal stem cells at dose 2x10^6 cells/kg MSCs on days 1 and day 7 (if needed) in addition to standard care
干预措施: Mesenchymal stem cells (Drug)
结局指标
主要结局
Overall survival
时间窗: 30 days post intervention
Assessment of Overall survival at 30 days post intervention
次要结局
- Clinical improvement(30 days)
- days required to discharge from hospital(30 days post admission)
- Radiological improvement (day 15 and day 30 assessment)(day 15 and day30)
- Time of COVID19 PCR negativity(day 1,3,7,10, 14)
研究者
Dr. Zaineb Akram
Research officer
National Institute of Blood and Marrow Transplant (NIBMT), Pakistan