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Trial registered on ANZCTR


Registration number
ACTRN12621000532808
Ethics application status
Approved
Date submitted
15/04/2021
Date registered
6/05/2021
Date last updated
6/05/2021
Date data sharing statement initially provided
6/05/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Vaccination of kidney transplant and dialysis patients and their close household contacts against COVID-19
Scientific title
Immunogenicity of the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and the BNT162b2 (Pfizer) COVID-19 Vaccines in a South Australian Cohort of Immunocompromised Patients and their Close Household Contacts
Secondary ID [1] 303962 0
None
Universal Trial Number (UTN)
Trial acronym
REVAX
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Kidney Transplant 321578 0
Dialysis 321579 0
Condition category
Condition code
Renal and Urogenital 319318 319318 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Immune responses in kidney transplant and dialysis patients are compared in each case with that of a close household contact (usually a spouse) over the age of 18.

This study is interventional in so much as close household contacts of transplant and dialysis patients will, in some instances, receive their vaccinations earlier than they otherwise would.

Both patients and cohabitants will be asked to provide up to four blood samples starting prior to-, and then up to 6 months post-, receipt of the initial ChAdOx1 nCoV-19 (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine. Blood samples will be collected at the Royal Adelaide Hospital by trained staff. Samples for some participants will be collected at the Queen Elizabeth Hospital or at SA Pathology collection centres as dictated by convenience.

Number and timing of vaccine doses received will not differ from that of the rest of the population i.e. an initial and booster dose, 21 days apart in the case of Pfizer-BioNTech and 12 weeks apart in the case of Oxford-AstraZeneca.

Participants will also be asked to provide a one-off stool sample prior to vaccination using a provided at-home collection kit. In conjunction with this, participants will be asked to complete a four-day food diary.

Participation in this study will amount to four appointments for blood collection, and two visits to vaccination clinics.
Intervention code [1] 320273 0
Early detection / Screening
Comparator / control treatment
In this study, cohabitants will act as reference comparators for the vaccine response of the transplant and dialysis patients.

Both patients and cohabitants will be asked to provide up to four blood samples starting prior to-, and then up to 6 months post-, receipt of the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine. Blood samples will be collected at the Royal Adelaide Hospital by trained staff. Samples for some participants will be collected at the Queen Elizabeth Hospital or at SA Pathology collection centres as dictated by convenience.

Number and timing of vaccine doses received will not differ from that of the rest of the population i.e. an initial and booster dose, 21 days apart in the case of Pfizer-BioNTech and 12 weeks apart in the case of Oxford-AstraZeneca.

Participants will also be asked to provide a one-off stool sample prior to vaccination using a provided at-home collection kit. In conjunction with this, participants will be asked to complete a four-day food diary.

Participation in this study will amount to four appointments for blood collection, and two visits to vaccination clinics.
Control group
Active

Outcomes
Primary outcome [1] 327186 0
Capacity of serum to neutralise SARS-CoV-2 spike protein-expressing pseudovirus will be assessed by a pseudovirus neutralisation assay.
Timepoint [1] 327186 0
Prior to initial vaccine dose, 20 days post initial vaccine dose, 20 days post vaccine booster dose (primary timepoint), 26 weeks post vaccine booster dose.
Primary outcome [2] 327187 0
Detectable seroconversion of IgG against SARS-CoV-2 spike protein and receptor-binding domain will be assessed by enzyme-linked immunosorbent assay.
Timepoint [2] 327187 0
Prior to initial vaccine dose, 20 days post initial vaccine dose, 20 days post vaccine booster dose (primary timepoint), 26 weeks post vaccine booster dose.
Primary outcome [3] 327188 0
SARS-CoV-2 spike protein-specific T cell response will be assessed by IFN-gamma ELISpot.
Timepoint [3] 327188 0
Prior to initial vaccine dose, 20 days post initial vaccine dose, 20 days post vaccine booster dose (primary timepoint), 26 weeks post vaccine booster dose.
Secondary outcome [1] 394116 0
SARS-CoV-2 spike protein-specific memory T cell quality and frequency will be assessed by activation-induced marker analysis by flow cytometry.
Timepoint [1] 394116 0
Prior to initial vaccine dose, 20 days post initial vaccine dose, 20 days post vaccine booster dose, 26 weeks post vaccine booster dose.
Secondary outcome [2] 394117 0
SARS-CoV-2 spike protein and RBD-specific memory B cell quality and frequency will be assessed by B cell tetramer staining for flow cytometric analysis,
Timepoint [2] 394117 0
Prior to initial vaccine dose, 20 days post initial vaccine dose, 20 days post vaccine booster dose, 26 weeks post vaccine booster dose.
Secondary outcome [3] 394477 0
Quality of the antibody response to SARS-CoV-2 spike protein receptor-binding domain will be assessed by enzyme-linked immunosorbent assay measuring specific IgM in participant serum.
Timepoint [3] 394477 0
Prior to initial vaccine dose, 20 days post initial vaccine dose, 20 days post vaccine booster dose, 26 weeks post vaccine booster dose.
Secondary outcome [4] 394478 0
Quality of the antibody response to SARS-CoV-2 spike protein receptor-binding domain will be assessed by enzyme-linked immunosorbent assay measuring specific IgG1 in participant serum.
Timepoint [4] 394478 0
Prior to initial vaccine dose, 20 days post initial vaccine dose, 20 days post vaccine booster dose, 26 weeks post vaccine booster dose.
Secondary outcome [5] 394479 0
Quality of the antibody response to SARS-CoV-2 spike protein receptor-binding domain will be assessed by enzyme-linked immunosorbent assay measuring specific IgG3 in participant serum.
Timepoint [5] 394479 0
Prior to initial vaccine dose, 20 days post initial vaccine dose, 20 days post vaccine booster dose, 26 weeks post vaccine booster dose.
Secondary outcome [6] 394480 0
Quality of the antibody response to SARS-CoV-2 spike protein receptor-binding domain will be assessed by enzyme-linked immunosorbent assay measuring specific IgA in participant serum.
Timepoint [6] 394480 0
Prior to initial vaccine dose, 20 days post initial vaccine dose, 20 days post vaccine booster dose, 26 weeks post vaccine booster dose.
Secondary outcome [7] 394481 0
Gut microbiome species diversity will be compared between participants who do and do not seroconvert in response to vaccination based on an Inverse Simpson diversity score derived from 16s ribosomal sequencing of genetic material extracted from stool samples.
Timepoint [7] 394481 0
The comparison will be made between baseline stool sample, sero-status measured at 20 days post initial vaccine dose, 20 days post vaccine booster dose, and 26 weeks post vaccine booster dose.

Eligibility
Key inclusion criteria
For patient group:
Have a current kidney transplant >3 months or currently on dialysis.
Have a close household contact able to participate.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
For patient group:
Prior exposure to SARS-CoV-2 (positive serology).
Have previously received a COVID-19 vaccination.
Due to receive a transplant within the ensuing 6 months.

Control/comparison group:
Prior exposure to SARS-CoV-2 (positive serology).
Have previously received a COVID-19 vaccination.

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
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
A priori power calculations were performed based on data from previously published vaccination studies.

Recruitment
Recruitment status
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)
SA
Recruitment hospital [1] 19265 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 19266 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 33845 0
5000 - Adelaide
Recruitment postcode(s) [2] 33846 0
5011 - Woodville

Funding & Sponsors
Funding source category [1] 308344 0
Charities/Societies/Foundations
Name [1] 308344 0
The Hospital Research Foundation
Address [1] 308344 0
1 Port Road, Adelaide, South Australia 5000
Country [1] 308344 0
Australia
Funding source category [2] 308429 0
University
Name [2] 308429 0
The University of Adelaide
Address [2] 308429 0
North Terrace, Adelaide, South Australia 5005
Country [2] 308429 0
Australia
Funding source category [3] 308430 0
Charities/Societies/Foundations
Name [3] 308430 0
Kidney, Transplant & Diabetes Research Australia
Address [3] 308430 0
1 Port Road, Adelaide, South Australia 5000
Country [3] 308430 0
Australia
Primary sponsor type
Government body
Name
Central Adelaide Local Health Network
Address
1 Port Road, Adelaide, South Australia 5000
Country
Australia
Secondary sponsor category [1] 309161 0
University
Name [1] 309161 0
University of Adelaide
Address [1] 309161 0
North Terrace, Adelaide, South Australia 5005
Country [1] 309161 0
Australia
Secondary sponsor category [2] 309163 0
Hospital
Name [2] 309163 0
Royal Adelaide Hospital
Address [2] 309163 0
1 Port Road, Adelaide, South Australia 5000
Country [2] 309163 0
Australia
Other collaborator category [1] 281739 0
Hospital
Name [1] 281739 0
Royal Prince Alfred Hospital (Transplantation Institute)
Address [1] 281739 0
50 Missenden Rd, Camperdown NSW 2050
Country [1] 281739 0
Australia
Other collaborator category [2] 281740 0
Other
Name [2] 281740 0
Basil Hetzel Institute
Address [2] 281740 0
37 Woodville Rd, Woodville South SA 5011
Country [2] 281740 0
Australia
Other collaborator category [3] 281741 0
Government body
Name [3] 281741 0
SA Pathology
Address [3] 281741 0
Frome Road, Adelaide, South Australia, 5000
Country [3] 281741 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308316 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 308316 0
136 North Terrace, Adelaide, South Australia 5000
Ethics committee country [1] 308316 0
Australia
Date submitted for ethics approval [1] 308316 0
01/03/2021
Approval date [1] 308316 0
11/03/2021
Ethics approval number [1] 308316 0
14541

Summary
Brief summary
This study aims to measure the efficacy of the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and BNT162b2 mRNA (Pfizer-BioNTech) COVID-19 vaccines in transplant recipients and patients on dialysis, and in their close household contacts. Early reports indicate that kidney transplant recipients receiving immunosuppressive medications have a reduced protective immune response to COVID-19 vaccines. This is of concern as these are the individuals most at risk. These patient groups are adept at avoiding exposure to pathogens out in the world, and are therefore most likely to be exposed to the SARS-CoV-2 virus via a close household contact e.g. a spouse.

In this study, transplant recipients and dialysis patients will receive their vaccination at the same time as a close household contact. By comparing the immune response of patient and cohabitant, we will develop an understanding of whether priority vaccination of household contacts is a worthwhile strategy for protecting transplant and dialysis patients from COVID-19 in the future.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110282 0
Prof Toby Coates
Address 110282 0
Royal Adelaide Hospital, 1 Port Road, Adelaide, SA 5000
Country 110282 0
Australia
Phone 110282 0
+61 439901856
Fax 110282 0
Email 110282 0
toby.coates@sa.gov.au
Contact person for public queries
Name 110283 0
Prof Toby Coates
Address 110283 0
Royal Adelaide Hospital, 1 Port Road, Adelaide, SA 5000
Country 110283 0
Australia
Phone 110283 0
+61 8 70740000
Fax 110283 0
Email 110283 0
toby.coates@sa.gov.au
Contact person for scientific queries
Name 110284 0
Prof Toby Coates
Address 110284 0
Royal Adelaide Hospital, 1 Port Road, Adelaide, SA 5000
Country 110284 0
Australia
Phone 110284 0
+61 439901856
Fax 110284 0
Email 110284 0
toby.coates@sa.gov.au

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?
No other documents available
Summary results
No Results