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Trial registered on ANZCTR


Registration number
ACTRN12620000676910p
Ethics application status
Submitted, not yet approved
Date submitted
9/06/2020
Date registered
15/06/2020
Date last updated
15/06/2020
Date data sharing statement initially provided
15/06/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Amnion cells for COVID-19 related respiratory failure
Scientific title
Allogeneic Amniotic Epithelial Cells for the Treatment of COVID-19 related respiratory failure, a pilot feasibility randomised controlled trial
Secondary ID [1] 301460 0
None
Universal Trial Number (UTN)
Trial acronym
ACCOLADE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 related respiratory failure 317776 0
Condition category
Condition code
Respiratory 315843 315843 0 0
Other respiratory disorders / diseases
Infection 315891 315891 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
8 million amniotic epithelial cells (hAECs) per kg bodyweight in saline containing 2% human serum albumin will be delivered intravenously over the course of an hour by a nurse under the supervision of an ICU consultant.
Intervention code [1] 317770 0
Treatment: Other
Comparator / control treatment
saline containing 2% human serum albumin
Control group
Placebo

Outcomes
Primary outcome [1] 324047 0
ventilator free days score (VFD, composite of mortality and ventilator-free days) at 21 days after randomisation based on patient medical records
Timepoint [1] 324047 0
21 days after randomisation
Primary outcome [2] 324048 0
daily change in P/F ratio based on patient medical records of ventilator settings
Timepoint [2] 324048 0
over the first 5 days following intervention
Secondary outcome [1] 383618 0
Sequential Organ Failure Assessment (SOFA) score
Timepoint [1] 383618 0
over 7-day period post intervention
Secondary outcome [2] 383619 0
ICU free survival based on patient medical records
Timepoint [2] 383619 0
day 21 post randomisation
Secondary outcome [3] 383620 0
Duration of mechanical ventilation in survivors based on patient medical records
Timepoint [3] 383620 0
hospital discharge or day 28
Secondary outcome [4] 383621 0
Intensive care unit length of stay based on patient medical records
Timepoint [4] 383621 0
hospital discharge or day 28, whichever comes first
Secondary outcome [5] 383622 0
Hospital length of stay based on patient medical records
Timepoint [5] 383622 0
hospital discharge or day 28, whichever comes first

Eligibility
Key inclusion criteria
Patients included in this study must satisfy ALL of the following criteria:
• Proven or highly suspected COVID-19 through a polymerase chain reaction (PCR) test of a nasal swab; or a negative PCR test with typical radiological finding or CT scan in the absence of alternate diagnoses; or patients with respiratory failure of infective origin admitted to ICU during the COVID-19 pandemic
• Receiving supplemental oxygen, due to respiratory failure, with PaO2/FiO2 ratio less than or equal to 200 (moderate to severe) or an SaO2 < 92% while receiving more than or equal to 4 litres of O2 via face mask.

Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded if they have ANY of the following:
• Less than 18 years old
• Have been intubated for more than 48 hours,
• Documented significant chronic obstructive airway disease
• Death is imminent and inevitable within 24 hours,
• Limitation of therapy includes no invasive mechanical ventilation,
• Severe global left ventricular dysfunction with an ejection fraction of <25%,
• Receiving extracorporeal support or is highly likely within the next 12 hours,
• Acute fulminant hepatitis

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Treating the primary outcome as a continuous response, 20 subjects in each arm are needed to detect a difference of one standard deviation with 85% power, 2-sided p value 0.05 (No available data on VFD with COVID-19 patients, a report from Seattle suggested ventilation time SD 3.7d). As this is a feasibility pilot study, the point estimate of 95% Confidence Interval for the primary outcomes will be used to describe the potential impact of AECs treatment when compared with vehicle administration.
All analysis will be on the intention-to-treat principle. Median regression will be used to assess the primary outcome. Bonferroni adjustment for multiplicity will be used for secondary outcomes. Standard statistics will be used to describe baseline data.
Binomial secondary outcomes including 28 days all-cause mortality will be assessed using logistic regression to derive odds ratios. Time from randomisation to intubation, and ICU stay will be analysed using sub-distribution hazard regression models to account for the competing risk of death.

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] 305894 0
Self funded/Unfunded
Name [1] 305894 0
Not applicable
Address [1] 305894 0
Funding being sought
Country [1] 305894 0
Primary sponsor type
Hospital
Name
Monash Health
Address
246 Clayton Road, Clayton, Victoria 3168
Country
Australia
Secondary sponsor category [1] 306353 0
None
Name [1] 306353 0
None
Address [1] 306353 0
None
Country [1] 306353 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 306152 0
Monash Health Human Ethics Committee
Ethics committee address [1] 306152 0
246 Clayton Road, Clayton, Victoria 3168
Ethics committee country [1] 306152 0
Australia
Date submitted for ethics approval [1] 306152 0
25/05/2020
Approval date [1] 306152 0
Ethics approval number [1] 306152 0

Summary
Brief summary
Already, there are five clinical trials registered at Monash Health to assess the safety and efficacy of allogeneic amniotic epithelial cells for (i) bronchopulmonary dysplasia; (ii) acute ischaemic stroke; (iii) compensated liver cirrhosis; and (iv) Crohn’s related perianal fistulas. To date, 27 individuals (17 neonates, 10 adults) have received allogeneic amniotic epithelial cells intravenously. No serious adverse events associated with cell administration or tumorigenesis have been reported. Preclinical biodistribution studies indicate that the AECs do not engraft and are not detected in any tissues after 5 days. Intravenous infusions of up to 8 million cells per kilogram have been well tolerated in extremely premature babies.
Based on our extensive preclinical and clinical expertise with AEC, we propose a Phase 1b/2a trial to assess the safety and efficacy of allogeneic AECs for the treatment of COVID-19 related respiratory illness and multi-organ complications.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 102890 0
Prof Yahya Shehabi
Address 102890 0
Intensive Care Unit, Monash Health
246 Clayton Road, Clayton, Victoria 3168
Country 102890 0
Australia
Phone 102890 0
+61 419296986
Fax 102890 0
Email 102890 0
yahya.shehabi@monashhealth.org
Contact person for public queries
Name 102891 0
A/Prof Rebecca Lim
Address 102891 0
The Ritchie Centre, Hudson Institute of Medical Research
27-31 Wright Street, Clayton, Victoria 3168
Country 102891 0
Australia
Phone 102891 0
+61 3 85722794
Fax 102891 0
Email 102891 0
rebecca.lim@monash.edu
Contact person for scientific queries
Name 102892 0
A/Prof Rebecca Lim
Address 102892 0
The Ritchie Centre, Hudson Institute of Medical Research
27-31 Wright Street, Clayton, Victoria 3168
Country 102892 0
Australia
Phone 102892 0
+61 3 85722794
Fax 102892 0
Email 102892 0
rebecca.lim@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
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 8186 0
Study protocol
Citation [1] 8186 0
Link [1] 8186 0
Email [1] 8186 0
yahya.shehabi@monashhealth.org
Other [1] 8186 0
Attachment [1] 8186 0
Type [2] 8187 0
Informed consent form
Citation [2] 8187 0
Link [2] 8187 0
Email [2] 8187 0
yahya.shehabi@monashhealth.org
Other [2] 8187 0
Attachment [2] 8187 0
Type [3] 8188 0
Ethical approval
Citation [3] 8188 0
Link [3] 8188 0
Email [3] 8188 0
yahya.shehabi@monashhealth.org
Other [3] 8188 0
Attachment [3] 8188 0
Summary results
No Results