The safety evaluation of placenta-derived mesenchymal stem cell transplantation after in vitro culture in patients with COVID-19 related acute respiratory distress syndrome
Design
The study is a single arm, non randomized, non-blinded Phase 1 clinical trial in 10 patients with COVID-19-induced early ARDS
Settings and conduct
PLMSCs are manufactured according to GMP rules in a cleanroom facility. After passing QC tests, 1 million/kg of PLMSCs are packed in a bag and injected intravenously (during 15 minutes). The injections are done in university hospitals which located in Tehran.
Participants/Inclusion and exclusion criteria
Inclusion Criteria:
The confirmed positive result of RT-PCR test for SARS-COV2 acute infection
Bilateral opacity of the lungs on CT scan
PaO2 / FiO2 ratio <200
Exclusion Criteria:
Presence of severe and irreversible disease with a life expectancy of fewer than 6 months
Moderate to severe liver failure (Childs-Pugh score>12)
History of chronic lung disease with PaCO2> 50 mmHg or history of oxygen consumption at home
Intervention groups
Patients with COVID-19-induced early ARDS will receive a single dose of approximately 1 million/kg human-derived placental mesenchymal stem cells intravenously in addition to routine treatments.
Main outcome variables
1. Acute complications of cell transplantation in the first 24 hours after transplantation and up to 28 days after treatment
2- Change in the severity of pneumonia during hospitalization up to 28 days after treatment
3- Changing the oxygen supply (PaO2 / FiO2) up to 28 days after treatment
4- Number of days of connection to the mechanical ventilation device and number of days of hospitalization in the ICU
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20200621047859N4
Registration date:2021-01-03, 1399/10/14
Registration timing:registered_while_recruiting
Last update:2021-01-03, 1399/10/14
Update count:0
Registration date
2021-01-03, 1399/10/14
Registrant information
Name
Ramin Sarrami Forooshani
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 8879 6003
Email address
rsf1351@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-10-28, 1399/08/07
Expected recruitment end date
2021-03-10, 1399/12/20
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Human Placenta-Derived Mesenchymal Stem Cell Transplantation in Acute Respiratory Distress Syndrome (ARDS) Caused by COVID-19: Phase I Clinical Trial)
Public title
The effects of mesenchymal stem cells in COVID-19
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
COVID-19 infection confirmed with positive PCR test results with clinical signs including respiratory distress, cough, fever, decreased blood oxygen saturation, and imaging results in favor of ARDS
Over 18 years of age
Bilateral opacity of lungs on CT scan
PaO2/FiO2 ratio < 200
Requires mechanical ventilation to increase oxygen saturation
Written informed consent (according to the patient's condition, in case of unconscious consent, the consent will be obtained from the patient's guardian).
Exclusion criteria:
Less than 18 years of age
More than 96 hours passed from the diagnosis of ARDS (Based on the Berlin definition of ARDS)
Pregnancy or breastfeeding
Presence of active malignancy which has been treated in the past two years
Presence of severe and irreversible disease with a life expectancy of less than 6 months
Moderate to severe liver failure (Childs-Pugh Score> 12)
History of chronic lung disease with PaCO2>50 mm Hg or history of oxygen consumption at home
Extensive trauma in the past 5 days
History of lung transplantation
Inability to provide informed consent or meet test conditions
Class 3 or 4 pulmonary hypertension (WHO classification)
History of pulmonary embolism or deep vein thrombosis (DVT) in the past three months
Age
From 18 years old
Gender
Both
Phase
1
Groups that have been masked
No information
Sample size
Target sample size:
20
Randomization (investigator's opinion)
Not randomized
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Single
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Research Ethics Committee of Motamed Cancer Institute Academic Center for Education Culture and Rese
Street address
No 146, South Ghandi, Vanaq Square, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1517964311
Approval date
2020-05-06, 1399/02/17
Ethics committee reference number
IR.ACECR.IBCRC.REC.1399.009
Health conditions studied
1
Description of health condition studied
Acute Respiratory Distress Syndrome
ICD-10 code
J80
ICD-10 code description
Acute respiratory distress syndrome
Primary outcomes
1
Description
Safety of PLMSCs intravenous injection
Timepoint
During hospitalization up to 28 days after treatment
Method of measurement
Physical examinations and blood tests
2
Description
Change the amount of oxygen supply
Timepoint
Up to 28 days after treatment
Method of measurement
Measurement of PaO2 / FiO2
3
Description
mortality
Timepoint
Up to 28 days after intervention
Method of measurement
The patients follow up
4
Description
Change in the severity of pneumonia
Timepoint
During hospitalization up to 28 days after treatment
Method of measurement
Physical examination - percentage of oxygen in the ventilator
Secondary outcomes
1
Description
Investigation of visceral insufficiency
Timepoint
Up to 28 days after transplantation
Method of measurement
Perform liver and kidney function tests on days 0, 7, 14 and 28
2
Description
C-reactive protein changes
Timepoint
Daily to +28
Method of measurement
Measurement of blood C-reactive protein
3
Description
Change in the number of lymphocytes
Timepoint
Day zero to week 12
Method of measurement
blood test
4
Description
Lung CT scan changes
Timepoint
Within 28 days after treatment
Method of measurement
Perform a CT scan of the lungs
5
Description
Duration of ICU admission
Timepoint
at the time of ICU discharge
Method of measurement
Number of admission days
Intervention groups
1
Description
Intervention group: Patients with resistant pneumonia caused by COVID-19 infection with acute symptoms of ARDS who have not responded to routine treatments. This group will receive about 10^6 cells/Kg Good manufacturing practices (GMP)-grade mesenchymal stem cells infusion over 10 minutes. The common treatments of patients will not be stopped.