ANZCTR - Registration

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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]

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

Condition category

Condition code

Respiratory

Other respiratory disorders / diseases

Infection

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]

Treatment: Other

Comparator / control treatment

saline containing 2% human serum albumin

Control group

Placebo

Outcomes

Primary outcome [1]

ventilator free days score (VFD, composite of mortality and ventilator-free days) at 21 days after randomisation based on patient medical records

Timepoint [1]

21 days after randomisation

Primary outcome [2]

daily change in P/F ratio based on patient medical records of ventilator settings

Timepoint [2]

over the first 5 days following intervention

Secondary outcome [1]

Sequential Organ Failure Assessment (SOFA) score

Timepoint [1]

over 7-day period post intervention

Secondary outcome [2]

ICU free survival based on patient medical records

Timepoint [2]

day 21 post randomisation

Secondary outcome [3]

Duration of mechanical ventilation in survivors based on patient medical records

Timepoint [3]

hospital discharge or day 28

Secondary outcome [4]

Intensive care unit length of stay based on patient medical records

Timepoint [4]

hospital discharge or day 28, whichever comes first

Secondary outcome [5]

Hospital length of stay based on patient medical records

Timepoint [5]

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

Sex

Both males and females

Can healthy volunteers participate?

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

29/06/2020

Actual

Date of last participant enrolment

Anticipated

30/06/2021

Actual

Date of last data collection

Anticipated

31/07/2021

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Not applicable

Address [1]

Funding being sought

Country [1]

Primary sponsor type

Hospital

Name

Monash Health

Address

246 Clayton Road, Clayton, Victoria 3168

Country

Australia

Secondary sponsor category [1]

None

Name [1]

None

Address [1]

None

Country [1]

Ethics approval

Ethics application status

Submitted, not yet approved

Ethics committee name [1]

Monash Health Human Ethics Committee

Ethics committee address [1]

246 Clayton Road, Clayton, Victoria 3168

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

25/05/2020

Approval date [1]

Ethics approval number [1]

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

Prof Yahya Shehabi

Address

Intensive Care Unit, Monash Health
246 Clayton Road, Clayton, Victoria 3168

Country

Australia

Phone

+61 419296986

Fax

[email protected]

Contact person for public queries

Name

Rebecca Lim

Address

The Ritchie Centre, Hudson Institute of Medical Research
27-31 Wright Street, Clayton, Victoria 3168

Country

Australia

Phone

+61 3 85722794

Fax

[email protected]

Contact person for scientific queries

Name

Rebecca Lim

Address

The Ritchie Centre, Hudson Institute of Medical Research
27-31 Wright Street, Clayton, Victoria 3168

Country

Australia

Phone

+61 3 85722794

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Doc. No.	Type	Email
8186	Study protocol	[email protected]
8187	Informed consent form	[email protected]
8188	Ethical approval	[email protected]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Dimensions AI	Amniotic fluid characteristics and its application in stem cell therapy: A review	2022	https://doi.org/10.18502/ijrm.v20i8.11752

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically