MSCs in COVID-19 ARDS

• Status: Active, not recruiting
• Trial end date: 2022-02-01
• Target enrollment: 0
• Participant gender: All

Summary

The mortality rate in SARS-CoV-2-related severe ARDS is high despite treatment with antivirals, glucocorticoids, immunoglobulins, and ventilation. Preclinical and clinical evidence indicate that MSCs migrate to the lung and respond to the pro-inflammatory lung environment by releasing anti-inflammatory factors reducing the proliferation of pro-inflammatory cytokines while modulating regulatory T cells and macrophages to promote resolution of inflammation. Therefore, MSCs may have the potential to increase survival in management of COVID-19 induced ARDS.

The primary objective of this phase 3 trial is to evaluate the efficacy and safety of the addition of the mesenchymal stromal cell (MSC) remestemcel-L plus standard of care compared to placebo plus standard of care in patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2. The secondary objective is to assess the impact of MSCs on inflammatory biomarkers.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Mesoblast, Inc.; National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Remestemcel-l

Criteria

Inclusion Criteria

• 18 years or older

• Patient has SARS-CoV-2 (COVID-19) confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR) assay or other diagnostic test

• Patient requiring mechanical ventilatory support with moderate to severe ARDS as determined by the following criteria (adapted from the Berlin criteria)

• Bilateral opacities must be present on a chest radiograph or computerized tomographic (CT) scan. These opacities are not fully explained by pleural effusions, lobar collapse, lung collapse, or pulmonary nodules.

• Respiratory failure not fully explained by cardiac failure or fluid overload.

• Moderate to severe impairment of oxygenation must be present, as defined by the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2). The severity of the hypoxemia defines the severity of the ARDS:

• Moderate ARDS: PaO2/FiO2 >100 mmHg and ≤200 mmHg, on ventilator settings that include PEEP ≥5 cm H2O OR

• Severe ARDS: PaO2/FiO2 ≤100 mmHg on ventilator settings that include PEEP ≥5 cm H2O

• High sensitivity C-Reactive Protein (hs-CRP) or CRP serum level >4.0 mg/dL

• Acute Physiologic and Chronic Health Evaluation (APACHE IV) score >5

• Creatinine clearance of ≥ 30 mL/minute OR a creatinine clearance of 20-29 mL/minute with urine output of ≥0.3 mLs/kg/hour over the last 8 hours or ≥500 mLs over the last 24 hours

• The patient or his/her legally authorized representative (LAR) is able to provide informed consent

Exclusion Criteria

• Currently receiving extracorporeal membrane oxygenation (ECMO) or high frequency oscillatory ventilation (HFOV)

• Females who are pregnant or lactating

• Patients with established positive bacterial blood cultures prior to enrollment or suspicion of superimposed bacterial pneumonia

• Patients with BMI >55

• Patients with untreated HIV infection

• Patients with malignancy who are within 12 months of active treatment with any chemotherapy, radiation or immunotherapy.

• Patients who have been intubated for more than 72 hours in total at the time of randomization

• Creatinine clearance less than 20 mL/minute or receiving renal replacement therapy

• LFTs (isolated ALT or AST) > 8x upper limit of normal or > 5x upper limit of normal in the setting of other liver function abnormalities (i.e., total bilirubin ≥ 2x upper limit of normal)

• Known hypersensitivity to DMSO or to porcine or bovine proteins

• History of prior respiratory disease with requirement for supplemental oxygen

• Any end-stage organ disease which in the opinion of the investigator may possibly affect the safety of remestemcel-L treatment

• Receiving an investigational cellular therapy agent