Clinical trial NCT04444271: Mesenchymal Stem Cell Infusion for COVID-19 Infection
Official title: Prospective, Randomized Phase 2 Clinical Trial of Mesenchymal Stem Cells(MSCs) for the Treatment of Coronavirus Disease 2019(COVID-19)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID-19
Keywords: Coronavirus
Mesenchymal Stem Cells
Survival
Lead sponsor: National Institute of Blood and Marrow Transplant (NIBMT), Pakistan
Sponsor class: OTHER_GOV
First posted: 2020-06-23
Enrollment: 20
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: 30 days post intervention
Secondary outcomes:
measure: Clinical improvement
timeFrame: 30 days
measure: Time of COVID19 PCR negativity
timeFrame: day 1,3,7,10, 14
measure: Radiological improvement (day 15 and day 30 assessment)
timeFrame: day 15 and day30
measure: days required to discharge from hospital
timeFrame: 30 days post admission
Other outcomes:
Locations:
city: Rawalpindi
country: Pakistan
facility: NIBMT
state: Punjab
Study officials:
affiliation: NIBMT
name: xanab akram
role: STUDY_CHAIR
References: