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| Name | Class |
|---|---|
| United States Department of Defense | FED |
| Harborview Injury Prevention and Research Center | OTHER |
| Oregon Health and Science University | OTHER |
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This is a Phase 2b, randomized, double-blind, placebo-controlled, multi-center study to assess the safety and efficacy of a single dose of Allogeneic Bone Marrow-derived Human Mesenchymal Stromal Cells (hMSCs) infusion in patients with Acute Respiratory Distress Syndrome (ARDS). This study is the extension of the Phase 1 pilot study (NCT01775774) and Phase 2a study (NCT02097641).
This clinical study design is a randomized, double-blinded, placebo-controlled Phase 2b clinical trial using a 10 million cell/kg dose of human Mesenchymal Stromal Cells (hMSCs). Subjects will be randomized in a 1:1 randomization scheme to receive hMSCs or cell reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40) as the placebo; the study will enroll 120 patients who achieve a stable clinical baseline and receive study product (either hMSCs or the placebo).
The Data and Safety Monitoring Board (DSMB) will review adverse outcomes and protocol compliance. A pre-specified interim review will occur after 60 subjects have been enrolled and received study product; enrollment will continue during the DSMB review. All pre-specified clinically important events and unexpected serious adverse events including death during hospitalization up to 60 days will be reported to the DSMB on an ongoing basis; the study will be stopped for a safety evaluation by the DSMB if they have any concerns or if three subjects have pre-specified clinically important events or unexpected serious adverse events except death since death will be common in this critically ill population due the nature of the underlying illness (e.g., ARDS).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Human Mesenchymal Stromal Cells | Experimental | A single dose of 10 million cells/kg predicted body weight (PBW) Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells will administered intravenously over approximately 60-80 minutes. |
|
| Cell Reconstitution Media | Experimental | A single dose of cell reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40) will administered intravenously over approximately 60-80 minutes. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Human Mesenchymal Stromal Cells | Biological | Immediately prior to administration, the study product will be thawed and diluted 1:1 with reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40). Additional reconstitution media is added to a final product volume of 300 mL. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Oxygenation Index (OI) | Change in OI from baseline over the 36 hours (6, 12, 18, 24, 30, 36 hours) following the initiation of the study product infusion. Lower values are considered better. | 36 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Acute Lung Injury Score (LIS) | Changes in the 4-point acute lung injury (LIS) score from the baseline to days 1, 2, 3 and 7, or on the last day of positive pressure ventilation prior to day 7. The LIS is a composite 4-point scoring system including the PaO2/FiO2, PEEP, lung compliance, and the extent of infiltrates on the chest X-ray. Each of the four components is categorized from 0 to 4, where a higher number is worse. The total Lung Injury Score is obtained by dividing the aggregate sum by the number of components used. |
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Inclusion Criteria:
Patients will be eligible for inclusion if they meet all of the below criteria within 14 days of initial ICU admission. Criteria 1-3 must all be present within a 24-hour time period and at the time of enrollment:
Acute onset (defined below) of:
A need for positive pressure ventilation by an endotracheal or tracheal tube with a PaO2/FiO2 ratio <250 mmHg and ≥5 cm H2O positive end-expiratory airway pressure (PEEP), as per the Berlin Criteria.
Bilateral infiltrates consistent with pulmonary edema (defined below) on the frontal chest radiograph, or bilateral ground glass opacities on a chest CT scan.
No clinical evidence of left atrial hypertension as a primary explanation for the bilateral pulmonary infiltrates.
If the cause of ARDS is trauma, additional inclusion criteria will include ONE of the following relevant risk factors for developing ARDS:
Exclusion Criteria:
Age less than 18 years
Greater than 72 hours since first meeting ARDS criteria per the Berlin definition of ARDS
Greater than 14 days since initial ICU admission
Inability to administer study product within 14 days of ICU admission
PaO2/FiO2 ≥ 250 mmHg after consent obtained and before study product is administered
Unable to obtain informed consent/no surrogate available
Pregnant or lactating
In custody of law enforcement officials
Burns > 20% of total body surface area
WHO Class III or IV pulmonary hypertension
History of cancer treatment in the last 2 years except for non-melanotic skin cancers
Underlying medical condition for which 6-month mortality is estimated to be > 50%
Moribund patient not expected to survive 24 hours
Advanced chronic liver disease (Child-Pugh Score > 12)
Severe chronic respiratory disease with the use of home oxygen
Severe traumatic brain injury - defined as:
Evidence of anoxic brain injury
History of stroke within the last 3 years
No intent/unwillingness to follow lung protective ventilation strategy
Currently receiving extracorporeal life support (ECLS) or high-frequency oscillatory ventilation (HFOV)
Anticipated extubation within 24 hours of enrollment
Clinical evidence of left atrial hypertension as measured by a pulmonary arterial wedge pressure > 18mmHg or left ventricular failure measured by an echocardiogram with a left ventricular ejection fraction less than 40%. Clinical judgement will determine if either of these measurements needs to be carried out.
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| Name | Affiliation | Role |
|---|---|---|
| Michael Matthay, MD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California Davis Medical Center | Sacramento | California | 95817 | United States | ||
| Zuckerberg San Francisco General Hospital and Trauma Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40728562 | Derived | Matthay MA, Zhuo H, Sarma A, Alipanah-Lechner N, Hendrickson C, Kornblith LZ, Schreiber M, Zonies D, Khan A, Robinson B, Johnson NJ, Ware LB, Guillamondegui O, Casey J, Moore L, Patel B, Kao L, Wade CE, Fox E, Cox C, Khawanja F, Aguillon Prada R, Hossri S, Callcut R, Albertson T, Delucchi KL, McMillan M, Langelier CR, Pati S, McKenna DH, Leroux C, Calfee CS, Liu KD. Treatment with Allogeneic Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome: A Double-Blind, Placebo-controlled, Multicenter Phase 2b Clinical Trial (STAT). Am J Respir Crit Care Med. 2026 Feb 1;212(3):428-439. doi: 10.1164/rccm.202411-2254OC. |
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We do not have plan to share IPD data to other researchers.
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| ID | Title | Description |
|---|---|---|
| FG000 | Human Mesenchymal Stromal Cells | A single dose of 10 million cells/kg predicted body weight (PBW) Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells will administered intravenously over approximately 60-80 minutes. Human Mesenchymal Stromal Cells: Immediately prior to administration, the study product will be thawed and diluted 1:1 with reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40). Additional reconstitution media is added to a final product volume of 300 mL. |
| FG001 | Cell Reconstitution Media | A single dose of cell reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40) will administered intravenously over approximately 60-80 minutes. Cell Reconstitution Media: 300 mL of reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Human Mesenchymal Stromal Cells | A single dose of 10 million cells/kg predicted body weight (PBW) Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells will administered intravenously over approximately 60-80 minutes. Human Mesenchymal Stromal Cells: Immediately prior to administration, the study product will be thawed and diluted 1:1 with reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40). Additional reconstitution media is added to a final product volume of 300 mL. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Oxygenation Index (OI) | Change in OI from baseline over the 36 hours (6, 12, 18, 24, 30, 36 hours) following the initiation of the study product infusion. Lower values are considered better. | Missing data are due to various causes: ventilated by PSV mode, not recorded, or expired. | Posted | Median | Inter-Quartile Range | cmH20/mmHg | 36 hours |
|
Adverse event data was collected through 28 days from study product infusion. Death data was collected up to 6 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Human Mesenchymal Stromal Cells | A single dose of 10 million cells/kg predicted body weight (PBW) Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells will administered intravenously over approximately 60-80 minutes. Human Mesenchymal Stromal Cells: Immediately prior to administration, the study product will be thawed and diluted 1:1 with reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40). Additional reconstitution media is added to a final product volume of 300 mL. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ECMO | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Deep Vein Thrombosis | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Michael Matthay | University of California San Francisco | 415-476-1079 | michael.matthay@ucsf.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 19, 2022 | Dec 5, 2024 | Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 28, 2022 | Dec 5, 2024 | SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 24, 2022 | Feb 17, 2023 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D012128 | Respiratory Distress Syndrome |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
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| Vanderbilt University Medical Center |
| OTHER |
| The University of Texas Health Science Center, Houston | OTHER |
| University of Minnesota | OTHER |
For this Phase 2b trial, after informed consent is given, an assignment will be made by computer-generated randomization to administer either hMSCs therapy or placebo with a 1:1 allocation to the hMSCs:placebo arms.
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|
|
| Cell Reconstitution Media | Biological | 300 mL of reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40) |
|
|
| 7 days |
| Pulmonary Dead Space Fraction | Pulmonary Dead Space at day 1, 2, 3 and 7. The dead-space fraction is calculated as: (PaCO2 - PeCO2) ÷ PaCO2 | 7 days |
| Change of Chest Radiograph Assessment of Pulmonary Edema (RALE Score) | Changes of RALE score at day 1, 2, 3 and 7 from baseline RALE score. To calculate RALE, each radiographic quadrant is scored for extent of consolidation (0-4) and density of opacification (1-3). The product of the consolidation and density scores for each of the four quadrants is summed. The RALE score ranges from 0 (best) to 48 (worst). | 7 days |
| Ventilator Free-days (VFD) Over 14 Days | Ventilator free-days over 14 days. Defined as the number of days from the time of initiating unassisted breathing to day 14 after study product administration, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 14. If a patient returns to assisted breathing and subsequently achieves unassisted breathing to day 14, VFDs will be counted from the end of the last period of assisted breathing to day 14. | 14 days |
| Ventilator Free-days (VFD) Over 28 Days. | Defined as the number of days from the time of initiating unassisted breathing to day 28 after study product administration, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 28. If a patient returns to assisted breathing and subsequently achieves unassisted breathing to day 28, VFDs will be counted from the end of the last period of assisted breathing to day 28. | 28 days |
| Duration of Assisted Ventilation Over 28 Days | Duration of assisted ventilation over 28 days in the survivors | 28 days |
| Percentage of Patients Achieving Pressure Support Ventilation for 2 Hours | Percentage of patients achieving pressure support ventilation equal to 5 cm H2O with positive end-expiratory pressure (PEEP) equal to 5 cm H2O for 2 hours | 28 days |
| Occurrence of Infection | Superficial incisional/wound infections, deep incisional wound infections, and organ/space infections, and ventilator associated pneumonia (all during the 14 days after enrollment) | 14 days |
| Occurrence of Thromboembolic Events | Thromboembolic events are measured by ultrasound of the deep venous system or CT-angiography of the chest ordered for clinical purposes/by treating clinicians | 60 days |
| Sequential Organ Failure Assessment (SOFA) Over 7 Days | SOFA score at 3 and 7 days. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems which are added up. Each score ranges from 0 to 4. SOFA score ranges from 0 (best) to 24 (worst). | 7 days |
| Non-pulmonary Sequential Organ Failure Assessment (SOFA) Over 7 Days | Non-pulmonary SOFA score at 3 and 7 days. The score is based on 5 different scores, one each for the cardiovascular, hepatic, coagulation, renal and neurological systems which are added up. Each score ranges from 0 to 4. SOFA score ranges from 0 (best) to 20 (worst). | 7 days |
| All-cause Mortality | All-cause mortality at 14, 28 and 60 days | 60 days |
| Glasgow Outcome Score (GCS) | Glasgow Outcome Score at hospital discharge. The GCS is a scale to evaluate level of consciousness in patients with acute brain injury. The scale assesses 3 functions: Eye Opening, Verbal Response, and Motor Response. GCS scores range from 15 (best) to 3 (worst) | 60 days |
| Plasma Angiopoietin-2 | Change in levels of plasma angiopoietin-2 from baseline at 6, 24, 48 and 72 hours since the initiation of the study product infusion. | 72 hours |
| Plasma Receptor for Advanced Glycation Endproducts (RAGE) | Change in levels of plasma RAGE from baseline at 6, 24, 48 and 72 hours since the initiation of the study product infusion. | 72 hours |
| Plasma Interleukin-6 (IL-6) | Change in levels of plasma interleukin-6 from baseline compared to 6, 24, 48 and 72 hours | 72 hours |
| Plasma Interleukin-8 (IL-8) | Change in levels of plasma interleukin-8 from baseline at 6, 24, 48 and 72 hours since the initiation of study product infusion. | 72 hours |
| Plasma Tumor Necrosis Factor Receptor 1 (TNFR-1) | Change in levels of plasma TNFR-1 from baseline at 6, 24, 48 and 72 hours since the initiation of study product infusion. | 72 hours |
| Plasma Protein C | Change in levels of plasma protein C from baseline at 6, 24, 48 and 72 hours since the initiation of study product infusion. | 72 hours |
| Plasma Angiopoietin-1 (ANG-1) | Change in levels of plasma angiopoietin-1 from the baseline to 6, 24, 48 and 72 hours since the initiation of study product infusion. | 72 hours |
| Plasma Lipoxin A4 | Change in levels of plasma lipoxin A4 from baseline compared to 6, 24, 48 and 72 hours | 72 hours |
| Plasma Resolvin D1 | Change in levels of plasma Resolvin D1 from baseline compared to 6, 24, 48 and 72 hours | 72 hours |
| Plasma Keratinocyte Growth Factor (KGF) | Change in levels of plasma KGF from baseline at 6, 24, 48 and 72 hours since the initiation of study product infusion. | 72 hours |
| Urine Microalbumin | Change in levels of urine microalbumin from baseline compared to 24 and 48 hours | 48 hours |
| Total Protein in Min-bronchoalveolar Lavage (mBAL) | Change in total protein levels in from baseline to day 2 | 2 days |
| Tolerability of the hMSCs - Incidence of Pre-specified Infusion-associated Events and Unexpected Severe Adverse Events | Tolerability of the hMSCs, defined as the incidence of pre-specified infusion-associated events and unexpected severe adverse events in ARDS patients treated with human MSCs | 24 hours |
| San Francisco |
| California |
| 94110 |
| United States |
| University of California San Francisco | San Francisco | California | 94143 | United States |
| Oregon Health & Science University | Portland | Oregon | 97239 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| Memorial Hermann Hospital - Texas Medical Center | Houston | Texas | 77030 | United States |
| Harborview Medical Center | Seattle | Washington | 98112 | United States |
| BG001 | Cell Reconstitution Media | A single dose of cell reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40) will administered intravenously over approximately 60-80 minutes. Cell Reconstitution Media: 300 mL of reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40) |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| COVID positive | Count of Participants | Participants |
|
| Primary Cause of ARDS | Count of Participants | Participants |
|
| Acute Physiology, Age, Chronic Health Evaluation (APACHE) III | The worst values within 24 hours prior to randomization were calculated for APACHE III score. The range of APACHE III score is from 0 to 299. In APACHE III scoring, the patient's age is worth up to 24, and chronic health history is worth up to 23 points, 17 physiologic variables are measured and may add up to a maximum of an additional 252 points. The higher score, the worse clinical outcome. | Data are missing in 5 patients because patients/surrogates refused to release AIDS data. | Mean | Standard Deviation | units on a scale |
|
| Non-pulmonary Sequential Organ Failure Assessment (SOFA) Score | The SOFA score comprises of the sum of six organ system components (respiratory, cardiovascular, hepatic, coagulation, renal and neurological) and scores range from 0 to 24 (each component ranges from 0 to 4), with higher values representing a worse organ dysfunction and morbidity. | Mean | Standard Deviation | units on a scale |
|
| Minute Ventilation | Mean | Standard Deviation | liter/min |
|
| PaO2:FiO2 | Mean | Standard Deviation | mmHg |
|
| Lung Injury Score | Lung Injury Score (LIS) is a validated 4-point score based on chest radiograph findings, PaO2/FiO2 ratio, PEEP and compliance. Scoring is performed for each individual component, and the score is the average of the 4 components. The scores range from 0 to 4, with higher values representing a worse lung injury. | Data missing in one patient due to no quadrant value available for lung injury score calculation. | Mean | Standard Deviation | units on a scale |
|
| Oxygenation Index | Oxygenation index calculated as: FiO2 (%) x Mean Airway Pressure (mmHg) / PaO2 (mmHg). The higher value, the worse clinical outcome. | Data missing in one patient treated with Cell Reconstitution Media (Placebo) because the patient had pressure support ventilation (PSV), and the oxygenation index was not calculated. | Mean | Standard Deviation | cmH20/mmHg |
|
| Ventilatory Ratio | Ventilatory ratio is a simple bedside measurement of ventilation, which is calculated using the following formula: minute ventilation (ml/min) × PaCO2 (mm Hg)]/(predicted body weight × 100 × 37.5). The higher value, the worse outcome. | Mean | Standard Deviation | ratio |
|
| Angiopoietin 2 (ANG-2) | Some baseline samples were not obtained during the COVID-19 pandemic due to local institutional policies. | Median | Inter-Quartile Range | pg/mL |
|
| Interleukin 6 (IL-6) | Some baseline samples were not obtained during the COVID-19 pandemic due to local institutional policies. | Median | Inter-Quartile Range | pg/mL |
|
| Interleukin 8 (IL-8) | Some baseline samples were not obtained during the COVID-19 pandemic due to local institutional policies. | Median | Inter-Quartile Range | pg/mL |
|
| Receptor for Advanced Glycation Endproducts (RAGE) | Some baseline samples were not obtained during the COVID-19 pandemic due to local institutional policies. | Median | Inter-Quartile Range | pg/mL |
|
| Tumor Necrosis Factor Receptor 1 (TNFR-1) | Some baseline samples were not obtained during the COVID-19 pandemic due to local institutional policies. | Median | Inter-Quartile Range | pg/mL |
|
| Protein C | Some baseline samples were not obtained during the COVID-19 pandemic due to local institutional policies. | Median | Inter-Quartile Range | pg/mL |
|
| OG001 | Cell Reconstitution Media | A single dose of cell reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40) will administered intravenously over approximately 60-80 minutes. Cell Reconstitution Media: 300 mL of reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40) |
|
|
|
| Secondary | Acute Lung Injury Score (LIS) | Changes in the 4-point acute lung injury (LIS) score from the baseline to days 1, 2, 3 and 7, or on the last day of positive pressure ventilation prior to day 7. The LIS is a composite 4-point scoring system including the PaO2/FiO2, PEEP, lung compliance, and the extent of infiltrates on the chest X-ray. Each of the four components is categorized from 0 to 4, where a higher number is worse. The total Lung Injury Score is obtained by dividing the aggregate sum by the number of components used. | LIS were calculated for patients who were intubated. | Posted | Mean | Standard Deviation | score on a scale | 7 days |
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| Secondary | Pulmonary Dead Space Fraction | Pulmonary Dead Space at day 1, 2, 3 and 7. The dead-space fraction is calculated as: (PaCO2 - PeCO2) ÷ PaCO2 | Due to the COVID-19 pandemic, the master majority of the enrolled patients had COVID-19, and it was not feasible to conduct the pulmonary dead space measurement because if would have increased the risk of spreading the COVID-19 virus to the health care workers, especially the respiratory therapists. Thus, this analysis is not available. | Posted | 7 days |
|
|
| Secondary | Change of Chest Radiograph Assessment of Pulmonary Edema (RALE Score) | Changes of RALE score at day 1, 2, 3 and 7 from baseline RALE score. To calculate RALE, each radiographic quadrant is scored for extent of consolidation (0-4) and density of opacification (1-3). The product of the consolidation and density scores for each of the four quadrants is summed. The RALE score ranges from 0 (best) to 48 (worst). | RALE scores are calculated by the available Chest X-ray photographs. | Posted | Median | Inter-Quartile Range | score on a scale | 7 days |
|
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| Secondary | Ventilator Free-days (VFD) Over 14 Days | Ventilator free-days over 14 days. Defined as the number of days from the time of initiating unassisted breathing to day 14 after study product administration, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 14. If a patient returns to assisted breathing and subsequently achieves unassisted breathing to day 14, VFDs will be counted from the end of the last period of assisted breathing to day 14. | Posted | Count of Participants | Participants | 14 days |
|
|
|
|
| Secondary | Ventilator Free-days (VFD) Over 28 Days. | Defined as the number of days from the time of initiating unassisted breathing to day 28 after study product administration, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 28. If a patient returns to assisted breathing and subsequently achieves unassisted breathing to day 28, VFDs will be counted from the end of the last period of assisted breathing to day 28. | Posted | Count of Participants | Participants | 28 days |
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| Secondary | Duration of Assisted Ventilation Over 28 Days | Duration of assisted ventilation over 28 days in the survivors | The analysis was conducted in the subgroup of patients who survived by 6 months. | Posted | Median | Inter-Quartile Range | days | 28 days |
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| Secondary | Percentage of Patients Achieving Pressure Support Ventilation for 2 Hours | Percentage of patients achieving pressure support ventilation equal to 5 cm H2O with positive end-expiratory pressure (PEEP) equal to 5 cm H2O for 2 hours | Posted | Count of Participants | Participants | 28 days |
|
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|
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| Secondary | Occurrence of Infection | Superficial incisional/wound infections, deep incisional wound infections, and organ/space infections, and ventilator associated pneumonia (all during the 14 days after enrollment) | Posted | Count of Participants | Participants | 14 days |
|
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|
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| Secondary | Occurrence of Thromboembolic Events | Thromboembolic events are measured by ultrasound of the deep venous system or CT-angiography of the chest ordered for clinical purposes/by treating clinicians | Posted | Count of Participants | Participants | 60 days |
|
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|
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| Secondary | Sequential Organ Failure Assessment (SOFA) Over 7 Days | SOFA score at 3 and 7 days. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems which are added up. Each score ranges from 0 to 4. SOFA score ranges from 0 (best) to 24 (worst). | Data were collected in the patients who were still in hospital alive. | Posted | Mean | Standard Deviation | score on a scale | 7 days |
|
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| Secondary | Non-pulmonary Sequential Organ Failure Assessment (SOFA) Over 7 Days | Non-pulmonary SOFA score at 3 and 7 days. The score is based on 5 different scores, one each for the cardiovascular, hepatic, coagulation, renal and neurological systems which are added up. Each score ranges from 0 to 4. SOFA score ranges from 0 (best) to 20 (worst). | Data were collected in the patients who were still in hospital alive. | Posted | Mean | Standard Deviation | score on a scale | 7 days |
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| Secondary | All-cause Mortality | All-cause mortality at 14, 28 and 60 days | 4 patients were lost of followup up to 60 days. | Posted | Count of Participants | Participants | 60 days |
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| Secondary | Glasgow Outcome Score (GCS) | Glasgow Outcome Score at hospital discharge. The GCS is a scale to evaluate level of consciousness in patients with acute brain injury. The scale assesses 3 functions: Eye Opening, Verbal Response, and Motor Response. GCS scores range from 15 (best) to 3 (worst) | 11 patients did not have recorded Glasgow Coma Scores at hospital discharge, all of them were expired. | Posted | Mean | Standard Deviation | score on a scale | 60 days |
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| Secondary | Plasma Angiopoietin-2 | Change in levels of plasma angiopoietin-2 from baseline at 6, 24, 48 and 72 hours since the initiation of the study product infusion. | Plasma samples were not collected due to institutional policies during COVID-19 pandemic, or not available at the required timepoints (e.g. discharged from hospital or death). | Posted | Median | Inter-Quartile Range | pg/mL | 72 hours |
|
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|
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| Secondary | Plasma Receptor for Advanced Glycation Endproducts (RAGE) | Change in levels of plasma RAGE from baseline at 6, 24, 48 and 72 hours since the initiation of the study product infusion. | Samples were not collected due to the intuitional policies regarding the biospecimen collection during COVID-19 pandemic, or not available at the required timepoint of collection (e.g. hospital discharge, death). | Posted | Median | Inter-Quartile Range | pg/mL | 72 hours |
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| Secondary | Plasma Interleukin-6 (IL-6) | Change in levels of plasma interleukin-6 from baseline compared to 6, 24, 48 and 72 hours | Samples were not collected due to the intuitional policies regarding the biospecimen collection during COVID-19 pandemic, or not available at the required timepoint of collection (e.g. hospital discharge, death). | Posted | Median | Inter-Quartile Range | pg/mL | 72 hours |
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| Secondary | Plasma Interleukin-8 (IL-8) | Change in levels of plasma interleukin-8 from baseline at 6, 24, 48 and 72 hours since the initiation of study product infusion. | Samples were not collected due to the intuitional policies regarding the biospecimen collection during COVID-19 pandemic, or not available at the required timepoint of collection (e.g. hospital discharge, death). | Posted | Median | Inter-Quartile Range | pg/mL | 72 hours |
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| Secondary | Plasma Tumor Necrosis Factor Receptor 1 (TNFR-1) | Change in levels of plasma TNFR-1 from baseline at 6, 24, 48 and 72 hours since the initiation of study product infusion. | Samples were not collected due to the intuitional policies regarding the biospecimen collection during COVID-19 pandemic, or not available at the required timepoint of collection (e.g. hospital discharge, death). | Posted | Median | Inter-Quartile Range | pg/mL | 72 hours |
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| Secondary | Plasma Protein C | Change in levels of plasma protein C from baseline at 6, 24, 48 and 72 hours since the initiation of study product infusion. | Samples were not collected due to the intuitional policies regarding the biospecimen collection during COVID-19 pandemic, or not available at the required timepoint of collection (e.g. hospital discharge, death). | Posted | Median | Inter-Quartile Range | pg/mL | 72 hours |
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|
| Secondary | Plasma Angiopoietin-1 (ANG-1) | Change in levels of plasma angiopoietin-1 from the baseline to 6, 24, 48 and 72 hours since the initiation of study product infusion. | Samples were not collected due to the intuitional policies regarding the biospecimen collection during COVID-19 pandemic, or not available at the required timepoint of collection (e.g. hospital discharge, death). | Posted | Median | Inter-Quartile Range | pg/mL | 72 hours |
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|
|
|
| Secondary | Plasma Lipoxin A4 | Change in levels of plasma lipoxin A4 from baseline compared to 6, 24, 48 and 72 hours | The majority of plasma samples were collected but some were not due to institutional policies on biospecimen collection during COVID-19 pandemic or because patients were no longer available (e.g. discharge, death). Plasma lipoxin A4 levels were not tested because the method depends on a complicated assay that is not validated for human use and is therefore unreliable. As a result, these samples have not been analyzed and will not be analyzed in the future. | Posted | 72 hours |
|
|
| Secondary | Plasma Resolvin D1 | Change in levels of plasma Resolvin D1 from baseline compared to 6, 24, 48 and 72 hours | The majority of plasma samples were collected but some were not due to institutional policies on biospecimen collection during COVID-19 pandemic or because patients were no longer available (e.g. discharge, death). Plasma resolvin D1 levels were not tested because the method depends on a complicated assay that is not validated for human use and is therefore unreliable. As a result, these samples have not been analyzed and will not be analyzed in the future. | Posted | 72 hours |
|
|
| Secondary | Plasma Keratinocyte Growth Factor (KGF) | Change in levels of plasma KGF from baseline at 6, 24, 48 and 72 hours since the initiation of study product infusion. | Most plasma samples were collected but some were not due to institutional restriction during the COVID-19 pandemic or patient unavailable (e.g. discharge, death). KGF doesn't accurately reflect biological activity of the mesenchymal stromal cell (MSC) treatment, and KGF assay is unreliable for determining the quantity released by MSCs (the therapeutic product) versus the release from endogenous cells within the patient. Thus, KGF levels have not been analyzed and will not analyzed in the future. | Posted | 72 hours |
|
|
| Secondary | Urine Microalbumin | Change in levels of urine microalbumin from baseline compared to 24 and 48 hours | The majority of urine samples were collected, but some were not due to institutional policies on biospecimen collection during the COVID-19 pandemic or because patients were no longer available (e.g., discharge, death). However, this measurement isn't reliable, as it doesn't accurately reflect kidney function or correlate intelligently with the effects of MSC therapy on kidney function. As a result, urine microalbumin levels were not analyzed and will not analyzed in the future. | Posted | 48 hours |
|
|
| Secondary | Total Protein in Min-bronchoalveolar Lavage (mBAL) | Change in total protein levels in from baseline to day 2 | The mini-BAL samples were not able to be collected during the COVID-19 pandemic due to local COVID policies and safety concerns. Collecting bronchoalveolar (BAL) samples would have been a major risk for spreading the COVID-19 virus to health care workers. | Posted | 2 days |
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| Secondary | Tolerability of the hMSCs - Incidence of Pre-specified Infusion-associated Events and Unexpected Severe Adverse Events | Tolerability of the hMSCs, defined as the incidence of pre-specified infusion-associated events and unexpected severe adverse events in ARDS patients treated with human MSCs | Posted | Count of Participants | Participants | 24 hours |
|
|
|
|
| 24 |
| 59 |
| 3 |
| 59 |
| 9 |
| 59 |
| EG001 | Cell Reconstitution Media | A single dose of cell reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40) will administered intravenously over approximately 60-80 minutes. Cell Reconstitution Media: 300 mL of reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40) | 21 | 61 | 2 | 61 | 6 | 61 |
| Asymmetric perfusion | Blood and lymphatic system disorders | Systematic Assessment |
|
| Partial hemorrhage | Nervous system disorders | Systematic Assessment |
|
| Tension pneumothorax | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| PEA arrest | Cardiac disorders | Systematic Assessment |
|
| Sepsis | Blood and lymphatic system disorders | Systematic Assessment |
|
| VAP Sepsis | Blood and lymphatic system disorders | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Aspiration pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Decrease in oxygen saturation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Agitation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Arrhythmia | Cardiac disorders | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | Systematic Assessment |
|
| C, diff infection | Gastrointestinal disorders | Systematic Assessment |
|
| Diplopia | Nervous system disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Day 2 |
|
|
| Day 3 |
|
|
| Day 7 |
|
|
| 0.37 |
| Superiority |
| The analysis is for the change of LIS from the baseline to day 3. | t-test, 2 sided | 0.54 | Superiority |
| The analysis is for the change of LIS from the baseline to day 7. | t-test, 2 sided | 0.19 | Superiority |
| Day 2 |
|
|
| Day 3 |
|
|
| Day 7 |
|
|
| 0.25 |
| Superiority |
| The analysis is for the change in RALE scores from the baseline to day 3. | Wilcoxon (Mann-Whitney) | 0.69 | Superiority |
| The analysis is for the change in RALE scores from the baseline to day 7. | Wilcoxon (Mann-Whitney) | 0.08 | Superiority |
| 5 - 9 days |
|
| 10 - 13 days |
|
| 10-15 days |
|
| 15-19 days |
|
| 20-24 days |
|
| 25-27 days |
|
| Ventilator associated pneumonia |
|
| Fisher Exact |
| 0.50 |
| Superiority |
| The analysis is for the percentages of patients who developed ventilator-associated pneumonia by day 14. | Fisher Exact | 0.20 | Superiority |
| Day 7 |
|
|
| 0.33 |
| Superiority |
| Day 7 |
|
|
| 0.26 |
| Superiority |
| 28-day mortality |
|
|
| 60-day mortality |
|
|
| Chi-squared |
| 0.83 |
| Superiority |
| The analysis is for the mortality between the two arms at Day 60. | Chi-squared | 0.56 | Superiority |
| 24 hour |
|
|
| 48 hour |
|
|
| 72 hour |
|
|
| Wilcoxon (Mann-Whitney) |
| 0.79 |
| Superiority |
| Plasma angiopoietin-2 changes from the baseline between two arms at 48 hours since the initiation of the study product infusion. | Wilcoxon (Mann-Whitney) | 0.62 | Superiority |
| Plasma angiopoietin-2 changes from the baseline between two arms at 72 hours since the initiation of the study product infusion. | Wilcoxon (Mann-Whitney) | 0.67 | Superiority |
| 24 Hour |
|
|
| 48 Hour |
|
|
| 72 Hour |
|
|
| Wilcoxon (Mann-Whitney) |
| 0.04 |
| Superiority |
| Plasma RAGE changes from the baseline between two arms at 48 hours since the initiation of the study product infusion. | Wilcoxon (Mann-Whitney) | 0.09 | Superiority |
| Plasma RAGE changes from the baseline between two arms at 72 hours since the initiation of the study product infusion. | Wilcoxon (Mann-Whitney) | 0.38 | Superiority |
| 24 Hour |
|
|
| 48 Hour |
|
|
| 72 Hour |
|
|
| Wilcoxon (Mann-Whitney) |
| 0.10 |
| Superiority |
| Plasma IL-6 changes from the baseline between two arms at 48 hours since the initiation of the study product infusion. | Wilcoxon (Mann-Whitney) | 0.15 | Superiority |
| Plasma IL-6 changes from the baseline between two arms at 72 hours since the initiation of the study product infusion. | Wilcoxon (Mann-Whitney) | 0.34 | Superiority |
| 24 Hour |
|
|
| 48 Hour |
|
|
| 72 Hour |
|
|
| Wilcoxon (Mann-Whitney) |
| 0.50 |
| Superiority |
| Plasma IL-8 changes from the baseline between two arms at 48 hours since the initiation of the study product infusion. | Wilcoxon (Mann-Whitney) | 0.64 | Superiority |
| Plasma IL-8 changes from the baseline between two arms at 72 hours since the initiation of the study product infusion. | Wilcoxon (Mann-Whitney) | 0.70 | Superiority |
| 24 Hour |
|
|
| 48 Hour |
|
|
| 72 Hour |
|
|
| Wilcoxon (Mann-Whitney) |
| 0.02 |
| Superiority |
| The analysis for the changes of TNFR-1 at 48 hours since the initiation of study product infusion from the baseline. | Wilcoxon (Mann-Whitney) | 0.02 | Superiority |
| The analysis for the changes of TNFR-1 at 72 hours since the initiation of study product infusion from the baseline. | Wilcoxon (Mann-Whitney) | 0.19 | Superiority |
| 24 Hour |
|
|
| 48 Hour |
|
|
| 72 Hour |
|
|
| Wilcoxon (Mann-Whitney) |
| 0.64 |
| Superiority |
| The analysis for the changes of Protein C at 48 hours since the initiation of study product infusion from the baseline. | Wilcoxon (Mann-Whitney) | 0.80 | Superiority |
| The analysis for the changes of Protein C at 72 hours since the initiation of study product infusion from the baseline. | Wilcoxon (Mann-Whitney) | 0.40 | Superiority |
| 24 Hour |
|
|
| 48 Hour |
|
|
| 72 Hour |
|
|
| Wilcoxon (Mann-Whitney) |
| 0.22 |
| Superiority |
| The analysis for the changes of ANG-1 at 48 hours since the initiation of study product infusion from the baseline. | Wilcoxon (Mann-Whitney) | 0.61 | Superiority |
| The analysis for the changes of ANG-1 at 72 hours since the initiation of study product infusion from the baseline. | Wilcoxon (Mann-Whitney) | 0.98 | Superiority |