Since the outbreak of coronavirusdisease2019(COVID-19), many researchers in China have carried out/published clinical trials on treatment based on Western medicine, traditional Chinese medicine or a combination of the two. Trials on treatment modalities have mainly used antivirals, interferon, glucocorticoids in addition to traditional Chinese medicine. There are also clinical trials exploring hydroxyquinoline/chloroquine sulphate, immunoglobulins, Vitamin-C, washed microbiota, nebulized interferon, teicoplanin as well as Mesenchymal stem cells. However, most of these trials were small (median sample size 100) and the bulk of potential therapeutic strategies remain in the experimental phase and currently there is no effective specific antiviral with high-level evidence.The aim of this study is assess the efficacy of MSCs as an add-on therapy to standard supportive treatment for patients with moderate/severe COVID-19.
All patients will receive 2x10^6 cells/kg on days 1 and day 7 (if needed). The study will be
divided in 2 phases. In the first phase, 10 patients will be included and randomized to 2
groups (5 Treatment arm; 5 Control Arm) and receive 2 x10^6 cells/kg MSCs on days 1 and 7 in
addition to standard care. Thereafter, the trial committee will meet and evaluate all
collected safety and efficacy information to decide about crossover of Control arm to
treatment arm if patient deteriorates clinically while in Control arm. Then, 10 new subjects
will be included in the study and treated according to protocol.
Preparation of MSCs doses MSCs will be isolated from bone marrow harvested cells. About 50ml
bone marrow will be collected from iliac crest using aseptic technique in syringes primed
with anticoagulant. The collected sample will be diluted with Phosphate Buffer Saline (PBS)
and MSCs will be separated using density gradient centrifugation. After resuspension the
cells will be seeded at a fixed concentration of 100,000 cells/cm2 in specially designed
flasks and incubated at 37oC in 5% carbondioxide (CO2). Medium will be changed after every
third day till harvesting of MSCs from the flasks. Once confluent (approximately day 20) the
cells will be harvested with sterile techniques using Trypsin- Ethylenediaminetetraacetic
acid ( EDTA ) solution. The prepared cells can either be stored in 50ml cryogenic vials for
future use or infused immediately.
Patient Selection and MSCs demand Patient for MSCs and Control arm will be selected by
multidisciplinary team (MDT) comprising Critical Care Specialist, Pulmonologist, Infectious
Disease Specialist, Clinical Hematologist.
1. Demand for MSCs will be initiated on pre-designated forms , signed by Critical care
Specialist Clearly indicating indication of MSCs.
2. Request form will be sent Stem Cell Lab.
3. Incharge stem Cell Lab will authorize issuance of the MSCs dose.
4. Stem Cell Lab will issue the dose Administration of MSCs
1. Experimental arm: Frozen MSCs will be resuspended in 100ml normal saline for immediate use
and given intravenously. The patients should be pre-medicated to avoid allergic reactions to
third party MSCs. Each patient in Experimental arm will be given 2 x 106 cells/kg will be
administered on day 1,7 in addition to supportive care 2. Control Arm: Will be Continued on
supportive care
Proposed usage:
Because of the very limited availability of MSCs, their usage has to be rationalized by MDT
comprising of pulmonologist, critical care specialist and clinical haematologist and
Infectious disease specialist.There is not enough evidence to put forth therapeutic
recommendations however, treatment decisions can be made on case to case basis after MDT.
Drug: Mesenchymal stem cells
1. Frozen MSCs will be resuspended in 100ml normal saline for immediate use and given intravenously. The patients should be pre-medicated to avoid allergic reactions to third party MSCs. Each patient in Experimental arm will be given 2 x 106 cells/kg will be administered on day 1,7 in addition to supportive care
Other Name: MSCs
Other: Placebo
100 ml of normal saline will be given intravenously to control arm
Inclusion Criteria:
1. Male or female, aged ≥ 10years
2. Laboratory confirmation of COVID19 infection by reverse-transcription polymerase chain
reaction (RT-PCR) from any diagnostic sampling source; and
3. Moderate illness: In compliance with the 2019-coronavirus pneumonia diagnosis standard
[according to the novel coronavirus infection pneumonia diagnosis and treatment
program (Trial Implementation Version 6) issued by the National Health and Medical
Commission, and world health organization (WHO) 2019 new coronavirus guidelines
standards]: (A) increased breathing rate (≥30 beats / min), difficulty breathing,
cyanosis of the lips; (B) in resting state, means oxygen saturation ≤93%; (C) partial
pressure of arterial oxygen (PaO2) / Fraction of inspired oxygen (FiO2) ≤300 mmHg
(1mmHg = 0.133kPa);
4. Critically ill : Respiratory failure, Septic Shock, muti-organ dysfunction syndrome
(MODS)
Exclusion Criteria:
1. Patients with systemic autoimmune diseases
2. Not consenting for clinical trial
3. Those declared not for resuscitation due to underlying comorbid or current critical
condition
NIBMT
Rawalpindi, Punjab, Pakistan
Investigator: Xanab Akram
Contact: 03325346564
xanab akram
03325346564
xanab.akram@gmail.com
xanab akram, Study Chair
NIBMT