Plain English Summary
Background and study aims
Many acutely ill patients are killed by severe acute respiratory distress syndrome (ARDS) and septic shock complicated with multiple organ failure. ARDS is a condition where the lungs can't provide the body's vital organs with enough oxygen. The causes of ARDS include infection, severe shock, trauma, aspiration injury, or severe systemic inflammation. Septic shock is when blood pressure drops to a dangerously low level after an infection. Many people eventually die of loss of multiple organ function. Even with prompt and proper antibiotic treatment, the death rate is quite high. It is important to find a new method to improve survival rates. Stem cells are able to regulate the immune system, are anti-inflammation and have the ability to repair tissues. The aim of this study to test the safety of human umbilical cord-derived mesenchymal stem cells in patients with ARDS and multiple organ failure complicating severe septic shock.
Who can participate?
Patients aged 20-80 with ARDS or severe septic shock, whose symptoms do not improve 5 days after traditional or standard treatment
What does the study involve?
Participants are randomly allocated to be treated with one of three doses of stem cells administered into their veins. The injected number of stem cells is gradually increased if safety is confirmed after injection of the lower dose. Safety is defined as no relevant side effects, such as allergy, immunosuppressant effect, or treatment-associated organ damage or death. The stem cell treatment takes less than 2 hours. After discharge, participants are followed up regularly in the outpatient setting at 1 month and every 3 months. The total follow-up period is one year.
What are the possible benefits and risks of participating?
The possible benefits of stem cell treatment include life-supporting or life-saving effects. The treatment may be used in future to protect organ function in critically ill patients. The relevant risks are irregular heart rhythm, heart attack, heart failure, brain ischemia, bleeding, anemia, worsening kidney function, electrolyte imbalance, malignancy, and so on. However, the reported rate of the above side effects is less than 1%.
Where is the study run from?
Kaohsiung Chang Gung Memorial Hospital (Taiwan)
When is the study starting and how long is it expected to run for?
December 2015 to November 2027
Who is funding the study?
Chang Gung Medical Research Program Grant (Taiwan)
Who is the main contact?
Prof. Hon-Kan Yip
han.gung@msa.hinet.net
Study website
Contact information
Type
Public
Contact name
Prof Hon-Kan Yip
ORCID ID
Contact details
No. 123
Ta Pei Road Niao Sung District
Kaohsiung
83301
Taiwan
+886 (0)7 731 7123 ext. 8300
han.gung@msa.hinet.net
Additional identifiers
EudraCT/CTIS number
IRAS number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Application of human umbilical cord-derived mesenchymal stem cells for patients with severe acute respiratory distress syndrome and/or profound septic shock complicated with multiple organ failure: a phase I clinical trial for evaluation of safety and tolerability
Acronym
HUCDMSC for patients with severe ARDS and/or septic shock
Study hypothesis
Human umbilical cord-derived mesenchymal stem cells (HUCDMSC) may be a therapeutic option for patients with ARDS and profound septic shock complicated with multiple organ failure.
Ethics approval(s)
Chang Gung Memorial Hospital, 16/04/2017, ref: 106-2457C
Study design
Prospective single-center interventional trial
Primary study design
Interventional
Secondary study design
Non randomised study
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Acute respiratory distress syndrome and/or profound septic shock complicated with multiple organ failure
Intervention
The eligible subjects who are willing to receive intravenous therapy with human umbilical cord-derived mesenchymal stem cells for ARDS and profound septic shock complicated with multiple organ failure will be enrolled into this study. Blood biochemistry study will be performed at baseline. Sequentially numbered opaque, sealed envelopes (SNOSE) will be used to allocate the study subjects. Three different dosages of human umbilical cord-derived mesenchymal stem cells will be administered intravenously:
1. 1.0 x 10(6) cells/kg (n=3)
2. 5.0 x 10(6) cells/kg (n=3)
3. 1.0 x 10(7) cells/kg (n=4)
The injected number of stem cells will be gradually titrated up if safety is confirmed after injection of the prior lower dose. The safety is defined as no relevant side effects after human umbilical cord-derived mesenchymal stem cell therapy, e.g., allergy, immunosuppressant effect, or therapy-associated organ damage or death. The duration of cell-based treatment with intravenous infusion of stem cells is less than 2 hours. After discharge, patients will be followed up regularly in the outpatient setting at 1 month and every 3 months. The total follow-up period is one year.
Intervention type
Biological/Vaccine
Pharmaceutical study type(s)
Phase
Phase I
Drug/device/biological/vaccine name(s)
human umbilical cord-derived mesenchymal stem cells
Primary outcome measure
1. Severity of ARDS and septic shock, assessed using APACHE II score at baseline
2. Organ function, assessed daily using SOFA score once daily from enrollment and until freedom from critical condition
3. GCS level, PaO2/FiO2, vital signs, level of serum Cr, ALT, total bilirubin, PT, APTT, platelet count, CRP, and lactate, measured using blood sample once daily from starting treatment
4. In-hospital mortality and 30-day mortality
5. Immune function and cytokine level assessed at baseline, the first 3 days, and one week later
Secondary outcome measures
Adverse events including immune response to stem cell therapy, hyperreactivity to HUCDMSC, anaphylactic shock, or incidental malignancy after cell-based therapy. After discharge, patients will be followed up regularly in the outpatient setting at 1 month and every 3 months. The total follow-up period is one year.
Overall study start date
15/12/2015
Overall study end date
30/11/2027
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Adult subjects aged 20-80 years with severe ARDS or profound septic shock complicated with multiple organ failure due to infection
2. Symptoms do not improve 5 days after traditional or standard therapy
3. Severe acute respiratory distress syndrome defined as acute onset, bilateral infiltration on chest X-ray, pulmonary wedge pressure ≤18 mmHg, and PaO2/FiO2 ≤200 mmHg
4. The definition of profound septic shock complicated with multiple organ failure was systolic blood pressure <90 mmHg with tissue hypoperfusion, combined with at least two organs failure (brain, lung, kidney, liver, or coagulation)
Participant type(s)
Patient
Age group
Adult
Lower age limit
20 Years
Upper age limit
80 Years
Sex
Both
Target number of participants
20 patients (10 patients with ARDS and the other 10 patients with septic shock and multiple organ failure)
Participant exclusion criteria
1. Age <20 or >80 years
2. Pregnant women
3. Malignancy
4. Autoimmune disease
5. Subjects not suitable for enrollment due to any reason evaluated by investigator
6. Patients who have joined other studies
Recruitment start date
27/07/2017
Recruitment end date
01/11/2027
Locations
Countries of recruitment
Taiwan
Study participating centre
Kaohsiung Chang Gung Memorial Hospital
No.123, Ta Pei Road, Niao Sung District
Kaohsiung
83301
Taiwan
Sponsor information
Organisation
Chang Gung Memorial Hospital, Chang Gung Medical Foundation
Sponsor details
No.5
Fuxing St.
Guishan Dist.
Taoyuan
33305
Taiwan
+886 (0)7 731 7123
mellee@cgmh.org.tw
Sponsor type
Hospital/treatment centre
Website
ROR
Funders
Funder type
Research organisation
Funder name
Chang Gung Medical Research Program Grant (grant no.: CMRPG8E1241)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
The trialists plan to report this trial results in a scientific journal in the future.
Intention to publish date
31/12/2028
Individual participant data (IPD) sharing plan
The data sharing plans for the current study are unknown and will be made available at a later date.
IPD sharing plan summary
Data sharing statement to be made available at a later date
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Interim results article | ARDS patients | 01/05/2020 | 21/05/2021 | Yes | No |