Single Donor Banked Bone Marrow Mesenchymal Stromal Cells for the Treatment of COVID-19 Induced ARDS: A Non-Blinded Randomized, Controlled Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Proportion of Participants With Treatment-related Serious Adverse Events (tSAEs)
研究概览
简要总结
***At this time, we are only enrolling at Houston Methodist Hospital (HMH)/Baylor College of Medicine (BCM) and are not shipping cells outside of BCM/HMH.***
This is a study for patients who have respiratory infection caused by SARS-CoV-2 that have not gotten better. Because there is no standard treatment for this infection, patients are being asked to volunteer for a gene transfer research study using mesenchymal stem cells (MSCs).
Stem cells are cells that do not yet have a specific function in the body. Mesenchymal stem cells (MSCs) are a type of stem cell that can be grown from bone marrow (the spongy tissue inside of bones). Stem cells can develop into other types of more mature (specific) cells, such as blood and muscle cells.
The purpose of this study is to see if MSCs versus controls can help to treat respiratory infections caused by SARS-CoV-2.
详细描述
Earlier, a healthy donor provided blood cells to generate MSCs. These cells were grown and frozen for later use.
Before being treated, the patient will receive a series of standard medical tests: These tests are done to assess the patient's eligibility to receive the cells.
- Physical exam and history
- SARS-CoV-2 test
- Blood tests
- Chest X-ray or chest CT Scan
- A urine pregnancy test, when applicable
The patient will be randomly assigned to a study group. We'll use a computer to put the patient into study group A (study drug) or group B (control) by chance (randomized). Patients randomized to the control group, will receive the standard treatment for their respiratory infection.
On the day that the patient is scheduled to receive the cells they will be pre-medicated with Benadryl and Tylenol. The patient will then receive an intravenous (into the vein) infusion of 1 x 10^8 cells/kg of MSCs. The patient will be monitored closely for two hours after the infusion. The patient will receive a second infusion at the same dose within 3-5 days of the initial infusion (at the discretion of the investigator) if there is no improvement in respiratory parameters or if there is a worsening of Acute respiratory distress syndrome (ARDS).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years or older
- •Confirmed SARS-CoV2 infection real-time reverse transcription polymerase chain reaction (RT-PCR) assay
- •Moderate OR severe ARDS, based on the degree of impairment of oxygenation as defined by the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2):
- •Moderate ARDS: PaO2/FiO2 100-200 mmHg OR
- •Severe ARDS: PaO2/FiO2 ≤100 mmHg
- •If on invasive or noninvasive (BiPAP) mechanical ventilator, PEEP ≥5 cm H2O
- •Bilateral opacities present on chest radiograph or computed tomographic (CT) scan, that are not fully explained by pleural effusions, lung collapse, or lung nodules.
排除标准
- •Currently receiving extracorporeal membrane oxygenation (ECMO)
- •Severe chronic respiratory disease requiring use of home oxygen
- •Pregnant or lactating
- •Known hypersensitivity to dimethyl sulfoxide (DMSO)
- •Unstable hemodynamics as deemed by the treating physician/investigator including but not limited to unstable, ventricular tachycardia or new cardiac arrythmia requiring cardioversion.
- •Uncontrolled bacterial or fungal co-infection
- •Any end-stage organ disease or condition, which in the opinion of the Investigator, makes the patient an unsuitable candidate for treatment
- •Inability to obtain informed consent (from patient or legally appropriate proxy)
- •Presence of any contraindication to receiving prophylactic low dose unfractionated or low molecular weight heparin.
- •Respiratory failure not fully explained by cardiac failure or fluid overload.
研究组 & 干预措施
Safety Run In
The study will first enroll and treat six patients with MSCs for safety run in. If no more than 2 treatment-related severe adverse events (tSAEs) are observed, the study will enroll and randomize additional patients in a ratio of 1:1 to receive either MSCs or routine/supportive care.
干预措施: Mesenchymal Stromal Cells (Biological)
Mesenchymal stromal cells
Patients randomized to the MSC arm will be administered an intravenous infusion of MSCs at a dose of 1 x 10^8. A second infusion will be allowed if the patient does not have improvement in respiratory parameters per discretion of the investigator, or ARDS clinically worsens, within 3-5 days following the initial infusion.
干预措施: Mesenchymal Stromal Cells (Biological)
Control Group
Patients randomized to the control arm will receive supportive care or treatment designated by their treating physicians.
干预措施: Supportive Care (Other)
结局指标
主要结局
Proportion of Participants With Treatment-related Serious Adverse Events (tSAEs)
时间窗: 28 days post cell infusion
Treatment-related serious adverse events (tSAE) are those directly related to the investigational infusion product. Adverse event grading will be per NCI Common Terminology Criteria for Adverse Events(CTCAE), vs 5. Rate of tSAEs in patients treated with MSCs will be reported as proportion and its 95% confidence interval.
Number of Participants With Improvement by at Least Two Categories on a Six Category Ordinal Scale at Day 14
时间窗: 14 days post cell infusion
Change by at least two categories on a six-category ordinal scale as improvement at day 14 post-randomization per protocol defined criteria. The six-category ordinal scale ranges from 6 to 1 with a higher score indicating a worse clinical outcome as follows: 6 ꞊ death; 5 ꞊ hospitalization, requiring extracorporeal membrane oxygenation (ECMO) and/or invasive mechanical ventilation (IMV); 4 ꞊ hospitalization, requiring non-invasive mechanical ventilation (NIV) and/or High-flow nasal cannula (HFNC) therapy; 3 = hospitalization, requiring supplemental oxygen (but not NIV/HFNC); 2 = hospitalization, not requiring supplemental oxygen; 1 = hospital discharge.
次要结局
- Number of Participants With Progression to Mechanical Ventilation or ECMO(28 days post cell infusion)
- Number of Oxygenation Free Days at Day 28(28 days post cell infusion)
- Duration of Hospital Stay(from the date of on study to the time of hospital discharge, death, or last follow-up, whichever occurred first. Up to 35 days.)
- Duration of Mechanical Ventilation and/or ECMO(28 days post cell infusion)
- Overall Survival(28 days post cell infusion)
- Clinical Status Determined by 6-point Ordinal Scale at Day 28(28 days post cell infusion)
- Severity of Acute Respiratory Distress Syndrome (ARDS) at Day 14(14 days post cell infusion)
- Duration of ICU Stay(from the date of admission or data of on study if the patient was admitted to ICU before enrollment to the time of ICU discharge, death, or last follow-up, whichever occurred first. Up to 35 days.)
- All-cause Mortality(28 days post cell infusion)
研究者
LaQuisa Hill
Assistant Professor
Baylor College of Medicine