Administration of Allogenic UC-MSCs as Adjuvant Therapy for Critically-Ill COVID-19 Patients
Ключевые слова
абстрактный
Описание
This study is a double blind, randomized control trial (RCT). This study will be concluded in 2 months, from May to July 2020, from subject selection to the end of follow up. Research subjects are obtained consecutively from Covid-19 patients who receive care in the intensive care unit (ICU) across four Covid-19 referral hospitals, including Persahabatan Hospital, Sulianti Saroso Center for Infectious Disease, Cipto Mangunkusumo General Hospital, and Universitas Indonesia Hospital, with 10 subjects obtained from each hospital and total 40 subjects for this RCT. Subjects from each hospitals are divided into control and experimental groups. Subject belongs to the control group will receive standardized therapy (consisting of oseltamivir and azithromycin), whereas subjects in the experimental group will receive MSCs infusion, in addition to standardized therapy.
Subject Criteria Inclusion Criteria for MSC Donor from Umbilical Cord:
Umbilical cord is collected from elective caesarean section from a fullterm pregnancies without any complication and free from HIV, Hepatitis B, C, D virus, Cytomegalovirus, Rubella Virus, and free from fungal and bacterial contamination.
Informed consent all of the subjects must be filled and signed up before ruled in this study.
As soon as after delivery, the umbilical cord is collected and processed in sterile specimen 0,9% NaCl at 4oC for 8 hours. The umbilical cord transported to the laboratory and cultured in GMP lab, at Stem Cells Medical Technology Integrated Service Unit Cipto Mangunkusumo Hospital. Cellular viability and proliferation are evaluated after cell characterization test by flow cytometer.
Sterility tests are done three times to ensure cellular sterility. Subjects will receive MSCs through infusion through intravenous for 1 hour, following the administration of diphenhydramine and anticoagulant to prevent clotting.
Following the MSCs administration, monitoring at the patients is carried out every day, whereas laboratory testing for basic parameters (complete blood count, differential count, blood gas analysis, C-reactive protein, SGOT/SGPT (AST/ALT), Ureum/Creatinine, eGFR, electrolyte, procalcitonin, albumin, total bilirubin, D-Dimer, fibrinogen, troponin I and proBNP) are carried out every three days. Cytokine levels are measured before the administration and 7th day after the administration. Chest radiography is carried out every three days.
Даты
Последняя проверка: | 06/30/2020 |
Первый отправленный: | 05/26/2020 |
Предполагаемая регистрация отправлена: | 07/01/2020 |
Первое сообщение: | 07/06/2020 |
Последнее обновление отправлено: | 07/01/2020 |
Последнее обновление опубликовано: | 07/06/2020 |
Фактическая дата начала исследования: | 06/30/2020 |
Предполагаемая дата завершения начальной школы: | 07/31/2020 |
Предполагаемая дата завершения исследования: | 08/31/2020 |
Состояние или болезнь
Вмешательство / лечение
Drug: Oseltamivir
Drug: Azithromycin
Biological: Experiment Group
Фаза
Группы рук
Рука | Вмешательство / лечение |
---|---|
Placebo Comparator: Control Group Patients receive standardized treatment, consisting of Oseltamivir and Azithromycin | |
Experimental: Experiment Group Patients receive intravenous infusion of 1x10^6 unit of umbilical-cord derived mesenchymal stem cells (UC-MSCs)/kgBW in 100 cc of 0.9% NaCl for 1 hour, in addition to standardized treatment | Biological: Experiment Group Adjuvant therapy on top of current standardized treatment (Oseltamivir + Azithromycin) |
Критерии приемлемости
Возраст, имеющий право на обучение | 18 Years Чтобы 18 Years |
Полы, имеющие право на обучение | All |
Принимает здоровых добровольцев | да |
Критерии | Inclusion Criteria: - Patients aged 18-95 years old - Confirmed for diagnosis of Covid-19 through RT-PCR from nasopharyngeal swab and/or bronchoalveolar lavage for patients under intubation - Laboratory results showed leukopenia and lymphopenic - Chest radiography shows pneumonia appearance and/or ground-glass opacity on chest CT-Scan - Patients/their families are willing to sign the informed consent Exclusion Criteria: - History of malignancy - Pregnant, or show positive result on pregnancy test - Patients was/are currently participating in other clinical trials within the last 3 months |
Результат
Основные показатели результатов
1. Clinical improvement: Presence of dyspnea [15 days]
2. Clinical improvement: presence of sputum [15 days]
3. Clinical improvement: fever [15 days]
4. Clinical improvement: ventilation status [15 days]
5. Clinical improvement: blood pressure [15 days]
6. Clinical improvement: heart rate [15 days]
7. Clinical improvement: respiratory rate [15 days]
8. Clinical improvement: oxygen saturation [15 days]
Меры вторичного результата
1. General laboratory outcome from leukocyte level [15 days]
2. General laboratory outcome from lymphocytes level [15 days]
3. General laboratory outcome from blood pH [15 days]
4. General laboratory outcome from blood level of CO2 [15 days]
5. General laboratory outcome from blood base excess level [15 days]
6. General laboratory outcome from blood oxygen partial pressure [15 days]
7. General laboratory outcome from blood level of HCO3 [15 days]
8. General laboratory outcome from blood level of O2 saturation [15 days]
9. General laboratory outcome from level of CRP [15 days]
10. General laboratory outcome from level of SGOT/SGPT (AST/ALT) [15 days]
11. General laboratory outcome from the level of ureum/creatinine level [15 days]
12. General laboratory outcome from the level of eGFR [15 days]
13. General laboratory outcome from the level of sodium [15 days]
14. General laboratory outcome from the level of potassium [15 days]
15. General laboratory outcome from the level of chloride [15 days]
16. Changes in procalcitonin level [15 days]
17. General laboratory outcome from albumin level [15 days]
18. General laboratory outcome from total bilirubin level [15 days]
19. Changes in D-Dimer level [15 days]
20. Changes in fibrinogen level [15 days]
21. Cardiac changes from troponin level [15 days]
22. Cardiac changes from NT proBNP level [15 days]
23. Changes in Leukemia Inhibiting Factor [7 days]
24. Changes in level of IL-6 [7 days]
25. Changes in level of IL-10 [7 days]
26. Changes in level of vascular endothelial growth factor (VEGF) [7 days]
27. Changes in level of ferritin [7 days]
28. Changes in level of CXCR3 [7 days]
29. Changes in level of CD4 [7 days]
30. Changes in level of CD8 [7 days]
31. Changes in level of CD56 [7 days]
32. Radiologic Improvement from Chest X-Ray/CT Scan [15 days]