COVID-19 ARDS - Medical / Health Care - Clinical Services
Phase 3 study assessing the Efficacy and Safety of Stempeucel® in Patients with Moderate to Severe ARDS due to COVID 19
Disease Overview
Lungs perform the critical function of supplying oxygen to every cell of the body, and consist of a combined structure of a basic architecture of terminal airways termed terminal bronchioles. The terminal structures are composed of several respiratory cell types including respiratory epithelial cells, endothelial cells, other stromal cells, and alveolar macrophages, as well as other organ-specific cells that commonly occur in the terminal structures of each organ. Therefore, the pathogenesis of ARDS is most simply described as extensive acute injury of a specific kind of respiratory cell directly by various insults, including infectious agents and/or host immune responses, or secondarily by ischemic insults, such as pulmonary thromboembolism or near-drowning. Mortality in COVID-19 infected patients with the inflammatory lung condition ARDS is reported to approach 50% and is associated with older age, co-morbidities such as diabetes, underlying lung disease/cardiovascular disease, higher disease severity and elevated markers of inflammation. In the absence of a proven effective therapy, current management consists of supportive care, including invasive and non-invasive oxygen support and treatment with antibiotics.
Management of ARDS
- While there are many medicines available to treat mild to moderate cases of COVID-19 patients, for treating Covid-19 ARDS patients, only limited options are available which includes ICU admission, high flow nasal canula oxygen therapy/ invasive or noninvasive ventilation and treatment which includes steroids, anti-coagulants and supportive measures to maintain euvolemia and to manage any complications.
- Patients with ARDS that are ventilated for an extended period of time and survive frequently experience long term pulmonary damage due to ventilator induced fibrosis and scarring, and also experience compromised quality of life.
- The current therapeutic interventions do not appear to be improving in-hospital survival. The mortality rate is high (>39%).Hence, there is a large unmet need for a safe and effective treatment for COVID-19 infected patients, especially the severe cases complicated with ARDS.
Mechanism of Action of Stempeucel
It is envisaged, Stempeucel® will reduce the fatal symptoms of COVID-19 induced pneumonia and progressing to ARDS
- Paracrine factors that modulate tissue repairs
- Anti - inflammatory effects on host cells
- Reduction of alveolar epithelium permeability in the lung
- Increased rate of alveolar fluid clearance
- Enhancement of host mononuclear cell phagocytic activity
- MSCs directly transfer mitochondrial DNA to host cells
- MSCs secrete micro vesicles
- MSCs resistant to viral infection by IFN stimulated genes
Clinical Trial Design
- Percent mortality 28 days after administration of BMMSCs
To assess the change from baseline to one year and two years follow-up as compared to the placebo arm in
- ICU free days 28 days after administration of BMMSCs
- Number of days alive and off ventilatory support at 28 days after administration of BMMSCs
- Oxygen index (OI) changes (from day 0 to day 14) (Oxygen index = FiO2 x MAP x 100 / PaO2)
- Acute Physiology And Chronic Health Evaluation (APACHE) II score (from Day 0 to Day 14)
- Sequential organ failure assessment score (SOFA score) (at day 0, 1, 3,7,14,and 28)
- Sequential organ failure assessment score (SOFA score) (at day 0, 1, 3,7,14,and 28)
- The type of adverse events AE(s), number of AE(s) and proportion of patients with AE(s).
- Assessment of clinical laboratory parameters.
- Physical examination findings and assessment of vital signs.
- Assessment of electrocardiogram (ECG) parameters.
- Plasma cytokines – IL -6, IL-8 and IL-10 (at day 0, day 4, 7, 14 and 28)
- Other markers in plasma – TNFα, D-dimer, LDH, hs-troponin, Pro-calcitonin, CRP (at day 0, 4, 7, 14 and 28)