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Trial registered on ANZCTR


Registration number
ACTRN12619001637134
Ethics application status
Approved
Date submitted
11/11/2019
Date registered
25/11/2019
Date last updated
17/12/2019
Date data sharing statement initially provided
25/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Cord blood therapy in premature babies: a safety and feasibility study
Scientific title
Autologous transplantation of umbilical cord blood derived stem cells in extreme preterm infants: protocol for a safety and feasibility study
Secondary ID [1] 299787 0
Nil known
Universal Trial Number (UTN)
Trial acronym
CORD-SAFE study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
preterm brain injury
315155 0
cerebral palsy 315156 0
Condition category
Condition code
Reproductive Health and Childbirth 313476 313476 0 0
Complications of newborn
Neurological 313529 313529 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cord blood collection and processing: Minimum cord blood collection volume for inclusion in the trial will be 9 mLs. The collected cord blood (>9 mLs) will be processed according to standard cell processing operating procedures, aliquoted and cryopreserved.

Storage and release: An aliquot containing sufficient numbers of UCBCs, according to weight of the preterm infant, required for early administration will be stored. Cell Care (Heatherton, VIC), a TGA accredited cord blood bank, will be responsible for collection, processing, storage of all samples and release of UCBC. Standard testing for impurities, cell viability and HLA matching of UCBC to the preterm infant’s HLA will be performed before release of UCBCs. Criteria for product release will include: free of microbial contamination after 7 days of culture, cell viability > 90% as determined by trypan blue exclusion at the time of cryopreservation, and HLA match from cord blood and infant sample.

Thawing and infusion preparation: On the day of infusion, UCBCs will be retrieved from liquid nitrogen storage, and once product release criteria are met, frozen UCBC aliquot will be transported to Monash Health. Cells will be thawed using a pre-warmed heat block for approximately 2 minutes. The UCBCs will be washed with dextrose/ albumin and centrifuged at 350g for 5 minutes prior to resuspension in dextrose/ albumin at the final desired concentration. The UCBCs will be suspended at a concentration 10% greater than the desired concentration to allow for cell loss. Volume of cell infusion prepared will be around 10 mL/kg. A final cell viability will be done just prior to administration.

Autologous transplantation of umbilical cord blood derived stem cells (intravenous)
UCBCs will be administered ONCE intravenously (through a peripheral intravenous catheter) at a dose of 25-50 million viable cells/ kg body weight, 25 million/kg being the proposed minimum dose, and 50 million/kg being the maximum dose.

UCBCs from autologous cord blood collection administered intravenously to infants, between D9 – D15 of life.
Intervention code [1] 316045 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 321941 0
Safety

Baby vital parameters, examinations and any adverse events in the first 48 hours after cell administration will be recorded on a specific case report form.

Adverse events could include a significant change in temperature, HR, RR, BP or a combination of these in first 24 hours of adminstration. Also, culture proven infection within first 48 hours of adminstration
Timepoint [1] 321941 0
Safety of autologous cell transplantation as evidenced by lack of adverse events in first 48 hours after transplantation
Primary outcome [2] 321942 0
Feasibility
Timepoint [2] 321942 0
Feasibility of access to enough cord blood in extreme premature infants and enough cord blood cells after processing
Secondary outcome [1] 376760 0
Composite neurological and neurodevelopmental outcomes till 2 years of age
Standardised assessment tools (General movements, Hammersmith infant neurological examination, and Bayley's Scale of Infant Development-IV)
Timepoint [1] 376760 0
Continuous, till 2 years of age.
Regular follow up at 6,12,18, and 24 months corrected age.
Secondary outcome [2] 376761 0
Characteristics of cord blood cells will be studied by flow cytometry, accounting for CD counts of cells. eg: CD1a, CD3, CD4, CD8, CD11b, CD11c, CD13, CD14, CD19, CD20, CD34, CD41a, CD41b, CD83, CD90, CD105 and CD133. This is a composite outcome
Timepoint [2] 376761 0
Once, at cord blood collection
Secondary outcome [3] 376762 0
Immune response to cell therapy based on blood tests done before and after transplantation
(namely IL-1b, IL-6, TNF-a and IL-10). This is a composite outcome
Timepoint [3] 376762 0
Day 1 post cell transplantation and 36 weeks post conceptional age

Eligibility
Key inclusion criteria
Extreme premature infants (<28 weeks gestation)
Minimum age
9 Days
Maximum age
16 Days
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Severe preterm brain injury (severe intraventricular haemorrhage, cystic periventricular leukomalacia)

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 304250 0
Hospital
Name [1] 304250 0
Monash Children's Hospital
Address [1] 304250 0
246 Clayton Road
Clayton 3168
Country [1] 304250 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
246 Clayton Rd
Clayton VIC 3168
Country
Australia
Secondary sponsor category [1] 304491 0
Commercial sector/Industry
Name [1] 304491 0
Cell Care
Address [1] 304491 0
42 Corporate Drive
Heatherton
VIC 3202
Country [1] 304491 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304706 0
Monash Health HREC
Ethics committee address [1] 304706 0
246 Clayton Rd
Clayton Vic 3168
Ethics committee country [1] 304706 0
Australia
Date submitted for ethics approval [1] 304706 0
11/11/2019
Approval date [1] 304706 0
13/12/2019
Ethics approval number [1] 304706 0
190000632A

Summary
Brief summary
Preterm brain injury continues to be an important complication of preterm birth, especially in extremely premature and extremely low birth weight infants. Umbilical cord blood derived stem cells (UCBCs) are being increasingly evaluated for their neuroprotective and neuroreparative properties. There remains a paucity of information on the feasibility and safety of autologous UCBC transplantation in extremely premature infants.

Methods: A single centre safety and feasibility study in preterm babies born before 28 weeks gestation. Cord blood will be collected after birth and, if sufficient blood is obtained, UCBC will be harvested from the cord blood, characterised and stored. After excluding infants who have already suffered severe preterm brain injury, preterm infants will be infused with autologous UCBC via the intravenous route at a dose of between 25-50 million UCBCs/kg body weight. A minimum of 20 infants will be administered autologous UCBCs. Primary outcomes will include feasibility and safety. Feasibility will be determined by access to sufficient cord blood at collection and UCBCs following processing. Safety will be determined by lack of adverse events directly related to autologous UCBC administration in the first few days after administration. Secondary outcomes studied will include neonatal, and neurodevelopmental morbidities till 2 years of life.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97942 0
Dr Atul Malhotra
Address 97942 0
Monash Chidlren's Hospital
246 Clayton Road
Clayton VIC 3168
Country 97942 0
Australia
Phone 97942 0
+61385723650
Fax 97942 0
Email 97942 0
atul.malhotra@monash.edu
Contact person for public queries
Name 97943 0
Dr Atul Malhotra
Address 97943 0
Monash Chidlren's Hospital
246 Clayton Road
Clayton VIC 3168
Country 97943 0
Australia
Phone 97943 0
+61385723650
Fax 97943 0
Email 97943 0
atul.malhotra@monash.edu
Contact person for scientific queries
Name 97944 0
Dr Atul Malhotra
Address 97944 0
Monash Chidlren's Hospital
246 Clayton Road
Clayton VIC 3168
Country 97944 0
Australia
Phone 97944 0
+61385723650
Fax 97944 0
Email 97944 0
atul.malhotra@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy
What supporting documents are/will be available?
No other documents available
Summary results
No Results