Phase 2
Completed N=8
Multiple Dosing of Mesenchymal Stromal Cells in Patients With ARDS (COVID-19)
Acute Respiratory Distress Syndrome · ARDS (Moderate or Severe) · COVID-19 pneumonia
Source: ClinicalTrials.gov NCT04466098 ↗
Enrolled (actual)
8
Serious AEs
37.5%
Results posted
Oct 2024
Primary outcomePrimary: Incidence of Grade 3-5 Infusional Toxicities and Predefined Hemodynamic or Respiratory Adverse Events Related to the Infusion of MSC — 0; 0 Participants
Summary
This is a multi-center, randomized, placebo controlled, interventional phase 2A trial to evaluate the safety profile and potential efficacy of multi-dosing of mesenchymal stromal cells (MSC) for patients with SARS-CoV-2 associated Acute Respiratory Distress Syndrome (ARDS). After informed consent, treatment assignment will be made by computer-generated randomization to administer either MSC or vehicle placebo control with a 2:1 allocation to the MSC: placebo arm.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Incidence of Grade 3-5 Infusional Toxicities and Predefined Hemodynamic or Respiratory Adverse Events Related to the Infusion of MSC |
0; 0 | — |
| SECONDARY Change in Biomarkers of Inflammation From Day 0 to Day 7 |
0; 0.4; -61; 102; 0; 2 | — |
| SECONDARY Trend Changes in PaO2:FiO2 Ratio |
-7; 8 | — |
| SECONDARY Trend Changes in Mean Airway Pressure |
-2.7; 0.3 | — |
| SECONDARY Trend Changes in Peak Pressure |
-0.28; 0.19 | — |
| SECONDARY Trend Changes in Plateau Pressure |
0.08; 0.38 | — |
| SECONDARY Trend Changes in Positive End-expiratory Airway Pressure (PEEP) |
-0.68; 0.14 | — |
| SECONDARY Incidence of Mortality |
2; 1 | — |
| SECONDARY Number of ICU-free Days |
3; 2; 1; 0; 1; 0 | — |
| SECONDARY Number of Days Alive and Ventilator Free |
3; 1; 0; 1; 1; 0 | — |
| SECONDARY Change in Acute Lung Injury (ALI) Score 2 |
-0.25; -1.5 | — |
| SECONDARY Incidence of Serious Adverse Events |
2; 1 | — |
| SECONDARY Number of Days Alive Off Supplemental Oxygen |
2; 1; 1; 0; 0; 1 | — |
Eligibility Criteria
Inclusion Criteria
- Age 18-80 years
- Meets 'Berlin Criteria' for diagnosis of moderate to severe ARDS for a minimum of 4 hours
- Less than 48 hours on a ventilator after meeting criteria for diagnosis of ARDS
- SARS-CoV-2 (proven by RT-PCR assay) with radiographic infiltrates
- PaO2/FiO2 5 cm H20
- Elevated C-reactive protein (above laboratory upper limit of normal)
- Meets organ function requirements, including left ventricular ejection fraction (LVEF) >35% ( as defined below)
- Off other investigational agents directed against inflammatory cytokines 48 hours prior to enrollment; agents directed against the replication of SARS-CoV-2 [e.g., Remdesivir] are permitted
- Voluntary informed consent in person or virtually by the patient or patient surrogate considering the face to face limitations during the COVID-19 pandemic and, given the nature of the study population, which frequently requires mechanical ventilation with sedation, surrogate consent will likely occur in a substantial proportion of the study population (this will remain a valid consent until the patient is fully alert, and aware, and can provide a second consent to continue participation in the study).
- Adequate organ function is defined as:
- Renal: Calculated estimated glomerular filtration rate >30 mL/min/1.73 m2 (on chemistry panel)
- Hepatic: Bilirubin 35%
Exclusion Criteria
- Ventilator support of FiO2 >0·8 or PEEP >20 cm H2O and ongoing use of more than two vasopressors for 2 or more hours with any agent at doses shown below in the supine position.
- Norepinephrine >12 μg/min or 0.2 μg/kg per min
- Phenylephrine >150 μg/min or 3 μg/kg per min
- Epinephrine >10 ug/min or 0.2 μg/kg per min
- Vasopressin >0.04 units/min
- Concurrent use of other investigational agents specifically for treatment of ARDS or inflammatory cytokines. (Note: Agents established to be efficacious and/or those used outside of formal trials are permitted as supportive data emerge)
- Known ineligibility for use of a ventilator for a minimum of 7 days, as judged by the institution's Triage Team
- Known allergy to MSC components: fetal calf serum, human albumin or DMSO
- Active invasive malignant disease requiring chemotherapy/radiation
- Other concurrent life-threatening disease (life expectancy <6 months) or eligible for hospice care
- Known history of HIV infection on active treatment
- Females who are pregnant or breastfeeding
- Current mean arterial pressure (MAP) <60 mmHg while on 2 or more vasopressors at above doses for more than 2 hours
- History of any significant cardiac (myocardial infarction within 12 months of screening visit or unstable angina), chronic ongoing hepatic, or renal disease (grade 3 or higher); diagnosis of congestive heart failure with hypoxemia primarily due to decompensated heart failure; diagnosis of severe chronic obstructive pulmonary disease (COPD) or interstitial lung disease requiring supplemental oxygen at home
- Concurrent diagnosis of diffuse alveolar hemorrhage
- Requiring continuous dialysis (unable to stop dialysis during study agent infusion)
Data sourced from ClinicalTrials.gov (NCT04466098). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.