Ann: EAP for Remestemcel-L in Children with MIS-C due to COVID-19, page-255

Agree @Opfan17 very comprehensive study. 90 days is the greatest time length for a secondary endpoint. Does this mean we will be waiting till September??? clarification appreciated.

Primary Outcome Measures :

1. Number of all-cause mortality [ Time Frame: 30 days ]
   Number of all-cause mortality within 30 days of randomization.

Secondary Outcome Measures :

1. Number of days alive off mechanical ventilatory support [ Time Frame: 60 days ]
   Number of days alive off mechanical ventilatory support calculated as the number of days, within the 60 days window, that patients were alive and free of mechanical ventilatory support.
2. Number of adverse events [ Time Frame: 30 days ]
   Safety analyses will be assessed by adverse event rates calculated as the ratio of the total number of events over 30 days divided by total patient-time at risk for the specific event from randomization.
3. Number of participants alive at day 7 [ Time Frame: 7 days ]
4. Number of participants alive at day 14 [ Time Frame: 14 days ]
5. Number of participants alive at day 60 [ Time Frame: 60 days ]
6. Number of participants alive at day 90[ Time Frame: 90 days ]
7. Number of participants with resolution and/or improvement of ARDS [ Time Frame: 7 days ]
   The number and percent of patients with resolution and/or improvement of ARDS at day 7
8. Number of participants with resolution and/or improvement of ARDS [ Time Frame: 14 days ]
   The number and percent of patients with resolution and/or improvement of ARDS at day 14
9. Number of participants with resolution and/or improvement of ARDS [ Time Frame: 21 days ]
   The number and percent of patients with resolution and/or improvement of ARDS at day 21
10. Number of participants with resolution and/or improvement of ARDS [ Time Frame: 30 days ]
    The number and percent of patients with resolution and/or improvement of ARDS at day 30
11. Change from baseline of the severity of ARDS [ Time Frame: baseline and 7 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 7 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
12. Change from baseline of the severity of ARDS [ Time Frame: baseline and 14 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 14 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
13. Change from baseline of the severity of ARDS [ Time Frame: baseline and 21 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 21 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
14. Change from baseline of the severity of ARDS [ Time Frame: baseline and 30 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 30 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
15. Length of stay [ Time Frame: 12 months ]
    Hospital length of stay
16. Clinical Improvement Scale [ Time Frame: 7 days ]
    Change from baseline in Clinical Improvement Scale at day 7. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
17. Clinical Improvement Scale [ Time Frame: 14 days ]
    Change from baseline in Clinical Improvement Scale at day 14. Full scale from 1 to 7, with higher score indicating more clinical improvement.
18. Clinical Improvement Scale [ Time Frame: 21 days ]
    Change from baseline in Clinical Improvement Scale at day 21. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
19. Clinical Improvement Scale [ Time Frame: 30 days ]
    Change from baseline in Clinical Improvement Scale at day 30. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
20. Change in serum hs-CRP concentration [ Time Frame: baseline and 7 days ]
    Changes from baseline in serum hs-CRP concentration at days 7
21. Change in serum hs-CRP concentration [ Time Frame: baseline and 14 days ]
    Changes from baseline in serum hs-CRP concentration at days 14
22. Change in serum hs-CRP concentration [ Time Frame: baseline and 21 days ]
    Changes from baseline in serum hs-CRP concentration at days 21
23. Change in serum hs-CRP concentration [ Time Frame: baseline and 30 days ]
    Changes from baseline in serum hs-CRP concentration at days 30
24. Change in IL-6 inflammatory marker level [ Time Frame: baseline and 7 days ]
    Changes from baseline in IL-6 inflammatory marker level at 7 days
25. Change in IL-6 inflammatory marker level [ Time Frame: baseline and 14 days ]
    Changes from baseline in IL-6 inflammatory marker level at 14 days
26. Change in IL-6 inflammatory marker level [ Time Frame: baseline and 21 days ]
    Changes from baseline in IL-6 inflammatory marker level at 21 days
27. Change in IL-6 inflammatory marker level [ Time Frame: baseline and 30 days ]
    Changes from baseline in IL-6 inflammatory marker level at 30 days
28. Change in IL-8 inflammatory marker level [ Time Frame: baseline and 7 days ]
    Changes from baseline in IL-6 inflammatory marker level at 7 days
29. Change in IL-8 inflammatory marker level [ Time Frame: baseline and 14 days ]
    Changes from baseline in IL-6 inflammatory marker level at 14 days
30. Change in IL-8 inflammatory marker level [ Time Frame: baseline and 21 days ]
    Changes from baseline in IL-6 inflammatory marker level at 21 days
31. Change in IL-8 inflammatory marker level [ Time Frame: baseline and 30 days ]
    Changes from baseline in IL-6 inflammatory marker level at 30 days
32. Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 7 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 7 days
33. Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 14 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 14 days
34. Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 21 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 21 days
35. Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 30 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 30 days
    
    while Im pasting walls of text, here are the inclusion criteria for revision:
    
    

    Criteria

    Inclusion Criteria

    • 18 years or older
    • Patient has coronavirus disease 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 computed 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) serum level >4.0 mg/dL
    • Acute Physiologic and Chronic Health Evaluation (APACHE IV) score >5
    • 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 untreated HIV infection
    • Patients who have been intubated for more than 72 hours
    • Creatinine clearance less than 30 mL/minute
    • LFTs (ALT or AST) > 5x 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